start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=42195 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elucidation of puberulic acid?induced nephrotoxicity using stem cell-based kidney organoids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent cases of acute kidney injury (AKI) in Japan have been linked to Beni-koji CholesteHelp supplements, with puberulic acid identified as a potential nephrotoxic contaminant. To address the need for a reliable in vitro nephrotoxicity testing platform, we developed a screening model using kidney organoids derived from adult rat kidney stem (KS) cells. The organoids were exposed to known nephrotoxicants, including cisplatin and gentamicin, to validate the system. Puberulic acid toxicity was evaluated in both KS cell-derived organoids and wild-type mice. The organoids recapitulated tubular injury induced by known nephrotoxins and showed significant Kim-1 mRNA upregulation. Puberulic acid-treated organoids and mice exhibited morphological features of acute tubular necrosis (ATN), mitochondrial damage, and reduced cytochrome c oxidase subunit IV (COX-IV) expression. Markers of oxidative stress and apoptosis, such as 8-hydroxy-2’-deoxyguanosine (8-OHdG) and cleaved caspase-3, were also elevated. These findings suggest that puberulic acid induces mitochondrial dysfunction and oxidative stress, leading to tubular cell death. Puberulic acid-induced nephrotoxicity was demonstrated using our kidney organoid model. KS cell-derived kidney organoids may provide a simple, reproducible, and rapid platform for nephrotoxicity assessment, which may complement conventional animal experiments. en-copyright= kn-copyright= en-aut-name=NakanohHiroyuki en-aut-sei=Nakanoh en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UchidaNaruhiko en-aut-sei=Uchida en-aut-mei=Naruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HaraguchiSoichiro en-aut-sei=Haraguchi en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Kidney organoid kn-keyword=Kidney organoid en-keyword=Kidney stem cell kn-keyword=Kidney stem cell en-keyword=Puberulic acid kn-keyword=Puberulic acid en-keyword=Nephrotoxicity kn-keyword=Nephrotoxicity en-keyword=Mitochondrial dysfunction kn-keyword=Mitochondrial dysfunction END start-ver=1.4 cd-journal=joma no-vol=786 cd-vols= no-issue= article-no= start-page=152753 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hydrogen-rich gas enhances mitochondrial membrane potential and respiratory function recovery in Caco-2 cells post-ischemia-reperfusion injury en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury.
Methods: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed.
Results: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1α and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion.
Conclusions: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions. en-copyright= kn-copyright= en-aut-name=SeyaMizuki en-aut-sei=Seya en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AokageToshiyuki en-aut-sei=Aokage en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MengYing en-aut-sei=Meng en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirayamaTakahiro en-aut-sei=Hirayama en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ObaraTakafumi en-aut-sei=Obara en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NojimaTsuyoshi en-aut-sei=Nojima en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshinoriKosaki en-aut-sei=Yoshinori en-aut-mei=Kosaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YumotoTetsuya en-aut-sei=Yumoto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WatanabeAkihiro en-aut-sei=Watanabe en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaTaihei en-aut-sei=Yamada en-aut-mei=Taihei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NaitoHiromichi en-aut-sei=Naito en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology kn-affil= affil-num=3 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=10 en-affil=Department of Emergency, Disaster and Critical Care Medicine, Hyogo Medical University kn-affil= affil-num=11 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Intestinal ischemia-reperfusion injury kn-keyword=Intestinal ischemia-reperfusion injury en-keyword=Molecular hydrogen kn-keyword=Molecular hydrogen en-keyword=Hydrogen gas therapy kn-keyword=Hydrogen gas therapy en-keyword=Caco-2 cells kn-keyword=Caco-2 cells en-keyword=Mitochondrial function kn-keyword=Mitochondrial function en-keyword=Hypoxia-inducible factor-1α (HIF1α) kn-keyword=Hypoxia-inducible factor-1α (HIF1α) END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=1 article-no= start-page=234 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251114 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rotenone targets midbrain astrocytes to produce glial dysfunction-mediated dopaminergic neurodegeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract=Exposure to pesticides, such as rotenone or paraquat, is an environmental factor that plays an important role in the pathogenesis of Parkinson's disease (PD). Rotenone induces PD-like pathology and is therefore used to develop parkinsonian animal models. Dopaminergic neurotoxicity caused by rotenone has been attributed to the inhibition of mitochondrial complex I, oxidative stress and neuroinflammation; however, the mechanisms underlying selective dopaminergic neurodegeneration by rotenone remain unclear. To resolve this, we focused on glial diversity and examined whether the brain region-specific glial response to rotenone could determine the vulnerability of dopaminergic neurons using primary cultured neurons, astrocytes and microglia from the midbrain and striatum of rat embryos and rotenone-injected PD model mice. Direct neuronal treatment with low-dose rotenone failed to damage dopaminergic neurons. Conversely, rotenone exposure in the presence of midbrain astrocyte and microglia or conditioned media from rotenone-treated midbrain glial cultures containing astrocytes and microglia produced dopaminergic neurotoxicity, but striatal glia did not. Surprisingly, conditioned media from rotenone-treated midbrain astrocytes or microglia monocultures did not affect neuronal survival. We also demonstrated that rotenone targeted midbrain astrocytes prior to microglia to induce dopaminergic neurotoxicity. Rotenone-treated astrocytes produced secreted protein acidic and rich in cysteine (SPARC) extracellularly, which induced microglial proliferation, increase in IL-1β and TNF-α, and NF-κB (p65) nuclear translocation in microglia, resulting in dopaminergic neurodegeneration. In addition, rotenone exposure caused the secretion of NFAT-related inflammatory cytokines and a reduction in the level of an antioxidant metallothionein (MT)-1 from midbrain glia. Furthermore, we observed microglial proliferation and a decrease in the number of MT-positive astrocytes in the substantia nigra, but not the striatum, of low-dose rotenone-injected PD model mice. Our data highlight that rotenone targets midbrain astrocytes, leading to SPARC secretion, which promotes the neurotoxic conversion of microglia and leads to glial dysfunction-mediated dopaminergic neurodegeneration. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImafukuFuminori en-aut-sei=Imafuku en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasaiKaori en-aut-sei=Masai en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomimotoKana en-aut-sei=Tomimoto en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SogawaChiharu en-aut-sei=Sogawa en-aut-mei=Chiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SogawaNorio en-aut-sei=Sogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Food and Health Sciences, Faculty of Environmental Studies, Hiroshima Institute of Technology kn-affil= affil-num=9 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pharmacotherapy, School of Pharmacy, Shujitsu University kn-affil= affil-num=11 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Rotenone kn-keyword=Rotenone en-keyword=Astrocyte kn-keyword=Astrocyte en-keyword=Microglia kn-keyword=Microglia en-keyword=SPARC kn-keyword=SPARC en-keyword=Parkinson's disease kn-keyword=Parkinson's disease END start-ver=1.4 cd-journal=joma no-vol=638 cd-vols= no-issue=8049 article-no= start-page=225 end-page=236 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immune evasion through mitochondrial transfer in the tumour microenvironment en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T?cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2,3,4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T?cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies. en-copyright= kn-copyright= en-aut-name=IkedaHideki en-aut-sei=Ikeda en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawaseKatsushige en-aut-sei=Kawase en-aut-mei=Katsushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeTomofumi en-aut-sei=Watanabe en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakenagaKeizo en-aut-sei=Takenaga en-aut-mei=Keizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InozumeTakashi en-aut-sei=Inozume en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshinoTakamasa en-aut-sei=Ishino en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkiSho en-aut-sei=Aki en-aut-mei=Sho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LinJason en-aut-sei=Lin en-aut-mei=Jason kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawashimaShusuke en-aut-sei=Kawashima en-aut-mei=Shusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagasakiJoji en-aut-sei=Nagasaki en-aut-mei=Joji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SuzukiShinichiro en-aut-sei=Suzuki en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MakinoshimaHideki en-aut-sei=Makinoshima en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ItamiMakiko en-aut-sei=Itami en-aut-mei=Makiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NakamuraYuki en-aut-sei=Nakamura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TatsumiYasutoshi en-aut-sei=Tatsumi en-aut-mei=Yasutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SuenagaYusuke en-aut-sei=Suenaga en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MorinagaTakao en-aut-sei=Morinaga en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=Honobe-TabuchiAkiko en-aut-sei=Honobe-Tabuchi en-aut-mei=Akiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OhnumaTakehiro en-aut-sei=Ohnuma en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KawamuraTatsuyoshi en-aut-sei=Kawamura en-aut-mei=Tatsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=UmedaYoshiyasu en-aut-sei=Umeda en-aut-mei=Yoshiyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=NakamuraYasuhiro en-aut-sei=Nakamura en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KiniwaYukiko en-aut-sei=Kiniwa en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=HayashiHidetoshi en-aut-sei=Hayashi en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=IkedaJun-ichiro en-aut-sei=Ikeda en-aut-mei=Jun-ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=HanazawaToyoyuki en-aut-sei=Hanazawa en-aut-mei=Toyoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=ManoHiroyuki en-aut-sei=Mano en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=SuzukiTakuji en-aut-sei=Suzuki en-aut-mei=Takuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=OsawaTsuyoshi en-aut-sei=Osawa en-aut-mei=Tsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=KawazuMasahito en-aut-sei=Kawazu en-aut-mei=Masahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= affil-num=1 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=2 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=3 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Division of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute kn-affil= affil-num=6 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=7 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=9 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=10 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan Department of Dermatology, Graduate School of Medicine, Chiba University kn-affil= affil-num=11 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Tsuruoka Metabolomics Laboratory, National Cancer Center kn-affil= affil-num=15 en-affil=Department of Surgical Pathology, Chiba Cancer Center kn-affil= affil-num=16 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=18 en-affil=Laboratory of Evolutionary Oncology, Chiba Cancer Center Research Institute kn-affil= affil-num=19 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=20 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=21 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=22 en-affil=Department of Dermatology, Faculty of Medicine, University of Yamanashi kn-affil= affil-num=23 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=24 en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center kn-affil= affil-num=25 en-affil=Department of Dermatology, Shinshu University School of Medicine kn-affil= affil-num=26 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=27 en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine kn-affil= affil-num=28 en-affil=Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University kn-affil= affil-num=29 en-affil=Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine kn-affil= affil-num=30 en-affil=Department of General Thoracic Surgery and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=31 en-affil=Division of Cellular Signalling, National Cancer Center Research Institute kn-affil= affil-num=32 en-affil=Department of Respirology, Graduate School of Medicine, Chiba University kn-affil= affil-num=33 en-affil=Division of Nutriomics and Oncology, RCAST, The University of Tokyo kn-affil= affil-num=34 en-affil=Division of Cell Therapy, Chiba Cancer Center Research Institute kn-affil= affil-num=35 en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3 article-no= start-page=147 end-page=155 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunometabolic Regulation of Innate Immunity in Systemic Lupus Erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pathogens or their components can induce long-lasting changes in the behavior of innate immune cells, a process analogous to “training” for future threats or environmental adaptation. However, such training can sometimes have unintended consequences, such as the development of autoimmunity. Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease characterized by the production of autoantibodies and progressive organ damage. Innate immunity plays a central role in its pathogenesis, contributing through impaired clearance of apoptotic cells, excessive type I interferon production, and dysregulated formation of neutrophil extracellular traps. Recent studies have revealed that metabolites and nucleic acids derived from mitochondria, a crucial energy production site, directly regulate type I interferon and anti-inflammatory cytokine production. These insights have fueled interest in targeting metabolic pathways as a novel therapeutic approach for SLE, offering promise for improving long-term patient outcomes. en-copyright= kn-copyright= en-aut-name=WatanabeHaruki en-aut-sei=Watanabe en-aut-mei=Haruki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoYoshinori en-aut-sei=Matsumoto en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=systemic lupus erythematosus kn-keyword=systemic lupus erythematosus en-keyword=interferon kn-keyword=interferon en-keyword=tricarboxylic acid cycle kn-keyword=tricarboxylic acid cycle en-keyword=innate immune memory kn-keyword=innate immune memory en-keyword=trained immunity kn-keyword=trained immunity END start-ver=1.4 cd-journal=joma no-vol=234 cd-vols= no-issue= article-no= start-page=125 end-page=132 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial content and mtDNA copy number in spermatozoa and penetrability into oocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The current narrative review aims to summarize the relation of mitochondrial content (MC) and mitochondrial DNA copy number (MDCN) in spermatozoa with sperm penetrability, and to discuss the various determining factors during the process of spermatogenesis in mammals. There are many potential factors associated with the quantitative alteration of MC and MDCN in male gametes from spermatogenesis to ejaculation. Particularly, spermatogenesis may be the first step to jointly contribute to an incomplete reduction of MC and MDCN in spermatozoon. It appears to be now quite clear that some abnormalities during spermatogenesis and oxidative stress are the main factors highly associated with the quantitative change of MC and MDCN in spermatozoa, consequently affecting sperm quality and their penetrability into oocytes. Currently, a series of proteins contributing to form sperm midpiece during spermatogenesis and cytoplasmic elimination during spermiation have been currently identified. The present review provides insight into how these factors interact with sperm MC and MDCN, and handholds to gain a better understanding of their roles. This review also highlights the uniqueness of normal fertile spermatozoa which have relatively lower MC and MDCN, but have mitochondria that function completely in multiple pivotal physiological pathways. en-copyright= kn-copyright= en-aut-name=NguyenHai Thanh en-aut-sei=Nguyen en-aut-mei=Hai Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DoSon Quang en-aut-sei=Do en-aut-mei=Son Quang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Animal Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Animal Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Animal Science, Okayama University kn-affil= en-keyword=Spermatozoa kn-keyword=Spermatozoa en-keyword=Mitochondria kn-keyword=Mitochondria en-keyword=Mitochondrial DNA kn-keyword=Mitochondrial DNA en-keyword=Penetrability kn-keyword=Penetrability en-keyword=Spermatogenesis kn-keyword=Spermatogenesis END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=2 article-no= start-page=835 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250120 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pathophysiology of Group 3 Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pulmonary hypertension associated with lung diseases and/or hypoxia is classified as group 3 in the clinical classification of pulmonary hypertension. The efficacy of existing selective pulmonary vasodilators for group 3 pulmonary hypertension is still unknown, and it is currently associated with a poor prognosis. The mechanisms by which pulmonary hypertension occurs include hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, a decrease in pulmonary vascular beds, endothelial dysfunction, endothelial-to-mesenchymal transition, mitochondrial dysfunction, oxidative stress, hypoxia-inducible factors (HIFs), inflammation, microRNA, and genetic predisposition. Among these, hypoxic pulmonary vasoconstriction and subsequent pulmonary vascular remodeling are characteristic factors involving the pulmonary vasculature and are the focus of this review. Several factors have been reported to mediate vascular remodeling induced by hypoxic pulmonary vasoconstriction, such as HIF-1 alpha and mechanosensors, including TRP channels. New therapies that target novel molecules, such as mechanoreceptors, to inhibit vascular remodeling are awaited. en-copyright= kn-copyright= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TayaSatoshi en-aut-sei=Taya en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurodaKazuhiro en-aut-sei=Kuroda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakayaYoichi en-aut-sei=Takaya en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TohNorihisa en-aut-sei=Toh en-aut-mei=Norihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakayamaRie en-aut-sei=Nakayama en-aut-mei=Rie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KatanosakaYuki en-aut-sei=Katanosaka en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YuasaShinsuke en-aut-sei=Yuasa en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pharmacy, Kinjo Gakuin University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=group 3 pulmonary hypertension kn-keyword=group 3 pulmonary hypertension en-keyword=hypoxic pulmonary vasoconstriction kn-keyword=hypoxic pulmonary vasoconstriction en-keyword=pulmonary vascular remodeling kn-keyword=pulmonary vascular remodeling END start-ver=1.4 cd-journal=joma no-vol=228 cd-vols= no-issue= article-no= start-page=30 end-page=36 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Exogenous expression of PGC-1α during in vitro maturation impairs the developmental competence of porcine oocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives of the current study were to examine the effects of exogenous expression of PGC-1α, which is a transcription factor responsive for controlling mitochondrial DNA (mtDNA) replication, mitochondria quantity control, mitochondrial biogenesis, and reactive oxygen species (ROS) maintenance, in porcine oocytes during in-vitro maturation (IVM) on the developmental competence, as well as mitochondrial quantity and function. Exogenous over-expression of PGC-1α by injection of the mRNA construct into oocytes 20 h after the start of IVM culture significantly increased the copy number of mtDNA in the oocytes, but reduced the incidences of oocytes matured to the metaphase-II stage after the IVM culture for totally 44 h and completely suppressed the early development in vitro to the blastocyst stage following parthenogenetic activation. The exogenous expression of PGC-1α also significantly induced spindle defects and chromosome misalignments. Furthermore, markedly higher ROS levels were observed in the PGC-1α-overexpressed mature oocytes, whereas mRNA level of SOD1, encoded for a ROS scavenging enzyme, was decreased. These results conclude that forced expression of PGC-1α successfully increase mtDNA copy number but led to increased ROS production, evidently by downregulation of SOD1 gene expression, inducement of spindle aberration/chromosomal misalignment, and consequently reduction in the meiotic and developmental competences of porcine oocytes. en-copyright= kn-copyright= en-aut-name=DoSon Quang en-aut-sei=Do en-aut-mei=Son Quang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NguyenHai Thanh en-aut-sei=Nguyen en-aut-mei=Hai Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Porcine kn-keyword=Porcine en-keyword=Mitochondria kn-keyword=Mitochondria en-keyword=Oocytes kn-keyword=Oocytes en-keyword=PGC-1 alpha kn-keyword=PGC-1 alpha en-keyword=In vitro maturation kn-keyword=In vitro maturation END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=3 article-no= start-page=e20220127 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=2023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rapid thawing of frozen bull spermatozoa by transient exposure to 70 °C improves the viability, motility and mitochondrial health en-subtitle= kn-subtitle= en-abstract= kn-abstract=Up to now, the definitive conclusion of the positive effects of rapid transient thawing at higher temperatures for shorter durations has not been obtained yet and is still under discussion due to some contradictory findings and limited assessment of post-thawed parameters. The purpose of the current study was to evaluate the effectiveness of rapid thawing in water at 70 °C by using various post-thawed parameters of frozen bull spermatozoa. Experiment 1, monitoring the change of temperature inside frozen bull straw thawed in water at different temperatures. Experiment 2, evaluation of various post-thawed characteristics of frozen bull spermatozoa thawed in water at different temperatures by using a computer-assisted sperm analysis, flow cytometry and immunocytochemistry. The time it took for the temperature inside the straw to warm up to 15 °C was nearly twice as faster when the straw was thawed in 70 °C water compared with 39 °C. Although there were differences among bulls, viability, motility, and mitochondrial membrane potential of spermatozoa thawed at 70 °C for 8 seconds and stabilized at 39 °C for 52 seconds were significantly higher than those of controls (thawed at 39 °C for 60 seconds) at 0 and 3 h after thawing. Just after thawing, however, there were no differences in acrosome integrity and distribution of phospholipase C zeta1, whereas mitochondrial reactive oxygen species production was significantly lower in spermatozoa thawed at 70 °C. From these results, we conclude that rapid thawing at 70 °C and then stabilization at 39 °C significantly improves viability, motility and mitochondrial health of bull spermatozoa rather than conventional thawing at 39 °C. The beneficial effect of rapid transient thawing could be due to shorter exposure to temperatures outside the physiological range, consequently maintaining mitochondrial health. en-copyright= kn-copyright= en-aut-name=NguyenHai Thanh en-aut-sei=Nguyen en-aut-mei=Hai Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DoSon Quang en-aut-sei=Do en-aut-mei=Son Quang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AthurupanaRukmali en-aut-sei=Athurupana en-aut-mei=Rukmali kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=bull semen kn-keyword=bull semen en-keyword=cryopreservation process kn-keyword=cryopreservation process en-keyword=phospholipase C zeta1 (PLCZ1) kn-keyword=phospholipase C zeta1 (PLCZ1) en-keyword=temperature of thawing kn-keyword=temperature of thawing END start-ver=1.4 cd-journal=joma no-vol=136 cd-vols= no-issue=2 article-no= start-page=63 end-page=68 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Metformin-induced mitochondrial reactive oxygen species and host defense mechanisms kn-title=メトホルミンによるミトコンドリア活性酸素誘導と生体防御機構 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name=鵜殿平一郎 kn-aut-sei=鵜殿 kn-aut-mei=平一郎 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Immunology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学学術研究院医歯薬学域 免疫学 en-keyword=CD8T 細胞 kn-keyword=CD8T 細胞 en-keyword=活性酸素 kn-keyword=活性酸素 en-keyword=Nrf2 kn-keyword=Nrf2 en-keyword=解糖系 kn-keyword=解糖系 en-keyword=ミトコンドリア kn-keyword=ミトコンドリア END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=11 article-no= start-page=6269 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Sprouty-related enabled/vasodilator-stimulated phosphoprotein homology 1 domain containing 2 (SPRED2) is an inhibitor of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and has been shown to promote autophagy in several cancers. Here, we aimed to determine whether SPRED2 plays a role in autophagy in hepatocellular carcinoma (HCC) cells. The Cancer Genome Atlas (TCGA) Liver Cancer Database showed a negative association between the level of SPRED2 and p62, a ubiquitin-binding scaffold protein that accumulates when autophagy is inhibited. Immunohistochemically, accumulation of p62 was detected in human HCC tissues with low SPRED2 expression. Overexpression of SPRED2 in HCC cells increased the number of autophagosomes and autophagic vacuoles containing damaged mitochondria, decreased p62 levels, and increased levels of light-chain-3 (LC3)-II, an autophagy marker. In contrast, SPRED2 deficiency increased p62 levels and decreased LC3-II levels. SPRED2 expression levels were negatively correlated with translocase of outer mitochondrial membrane 20 (TOM20) expression levels, suggesting its role in mitophagy. Mechanistically, SPRED2 overexpression reduced ERK activation followed by the mechanistic or mammalian target of rapamycin complex 1 (mTORC1)-mediated signaling pathway, and SPRED2 deficiency showed the opposite pattern. Finally, hepatic autophagy was impaired in the liver of SPRED2-deficient mice with hepatic lipid droplet accumulation in response to starvation. These results indicate that SPRED2 is a critical regulator of autophagy not only in HCC cells, but also in hepatocytes, and thus the manipulation of this process may provide new insights into liver pathology. en-copyright= kn-copyright= en-aut-name=WangTianyi en-aut-sei=Wang en-aut-mei=Tianyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GaoTong en-aut-sei=Gao en-aut-mei=Tong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=autophagy kn-keyword=autophagy en-keyword=mitophagy kn-keyword=mitophagy en-keyword=SPRED proteins kn-keyword=SPRED proteins en-keyword=MAPK/ERK kn-keyword=MAPK/ERK en-keyword=mTOR kn-keyword=mTOR en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=3 article-no= start-page=259 end-page=270 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202406 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol?disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients’ sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol?disulfide homeostasis and ischaemia-modified albumin were measured.
We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol?disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol?disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol?disulfide homeostasis in multiple sclerosis patients. en-copyright= kn-copyright= en-aut-name=VuralGonul en-aut-sei=Vural en-aut-mei=Gonul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DemirEsra en-aut-sei=Demir en-aut-mei=Esra kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=GumusyaylaSadiye en-aut-sei=Gumusyayla en-aut-mei=Sadiye kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ErenFunda en-aut-sei=Eren en-aut-mei=Funda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=BarakliSerdar en-aut-sei=Barakli en-aut-mei=Serdar kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NeseliogluSalim en-aut-sei=Neselioglu en-aut-mei=Salim kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ErelOzcan en-aut-sei=Erel en-aut-mei=Ozcan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University kn-affil= affil-num=2 en-affil=Department of Neurology, Ankara City Hospital kn-affil= affil-num=3 en-affil=Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University kn-affil= affil-num=4 en-affil=Department of Clinical Biochemistry, Ankara City Hospital kn-affil= affil-num=5 en-affil=Department of Neurology, Ankara City Hospital kn-affil= affil-num=6 en-affil=Department of Clinical Biochemistry, Ankara City Hospital kn-affil= affil-num=7 en-affil=Department of Clinical Biochemistry, Ankara City Hospital kn-affil= en-keyword=multiple sclerosis kn-keyword=multiple sclerosis en-keyword=dysfunctional HDL kn-keyword=dysfunctional HDL en-keyword=thiol?disulfide homeostasis kn-keyword=thiol?disulfide homeostasis en-keyword=cognitive decline kn-keyword=cognitive decline END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=染色体/クロマチン凝集塊移植: ミトコンドリアの持ち込みを最小限に抑えたミトコンドリア置換のための新規アプローチ-ヒト染色体凝集塊移植に対するマウス実験の意味するもの kn-title=Aggregated chromosomes/chromatin transfer: a novel approach for mitochondrial replacement with minimal mitochondrial carryover: the implications of mouse experiments for human aggregated chromosome transfer en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OKAMOTORyota en-aut-sei=OKAMOTO en-aut-mei=Ryota kn-aut-name=岡本遼太 kn-aut-sei=岡本 kn-aut-mei=遼太 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue=4 article-no= start-page=1317 end-page=1332 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antitumor activity of α-pinene in T-cell tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeu-tic agents have been developed, their therapeutic effects are suboptimal. α- Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic ma-lignancies. This report provides a comprehensive analysis of the potential benefits of using α- pinene as an antitumor agent for the treatment of T-cell tumors. We found that α- pinene inhibited the proliferation of hematologic malignancies, especially in T- cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and re-active oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α- pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted. en-copyright= kn-copyright= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraMaiko en-aut-sei=Kimura en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukuiChie en-aut-sei=Fukui en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaDaisuke en-aut-sei=Yamada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyakeMasayuki en-aut-sei=Miyake en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AoeMichinori en-aut-sei=Aoe en-aut-mei=Michinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsudaMasayuki en-aut-sei=Matsuda en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoriyamaTakashi en-aut-sei=Moriyama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsumuraAkifumi en-aut-sei=Matsumura en-aut-mei=Akifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Hematology, Department of Medicine, Kobe University Hospital kn-affil= affil-num=5 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=alpha-pinene kn-keyword=alpha-pinene en-keyword=apoptosis kn-keyword=apoptosis en-keyword=hematologic malignancies kn-keyword=hematologic malignancies en-keyword=lymphoblastic leukemia, acute, T-cell kn-keyword=lymphoblastic leukemia, acute, T-cell en-keyword=T-cell lymphoma kn-keyword=T-cell lymphoma END start-ver=1.4 cd-journal=joma no-vol=210 cd-vols= no-issue= article-no= start-page=154 end-page=161 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231015 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Negative correlations of mitochondrial DNA copy number in commercial frozen bull spermatozoa with the motility parameters after thawing en-subtitle= kn-subtitle= en-abstract= kn-abstract=The purpose of the current study was to investigate the relationship between mitochondrial content of commercial frozen-thawed bull spermatozoa and motility. Firstly, mitochondrial DNA copy number per spermatozoon (MDCN), mitochondrial content (MC), the percentage of spermatozoa with high mitochondrial membrane potential (HMMP), intracellular reactive oxygen species (ROS) and motility parameters of frozen-thawed spermatozoa derived from five bulls were determined by using qPCR, flow cytometry and CASA, respectively, and analyzed the relationships. Results showed that all parameters examined, including MDCN, MC, HMMP, ROS and motility indicators, significantly differed among frozen spermatozoa from different bulls. Both MDCN and MC were negatively correlated with HMMP and motility indicators, but positively with ROS, of course, whereas there was a highly positive relationship between MDCN and MC. Secondly, when MDCN and MC were examined in frozen spermatozoa prepared at different points in the lives of four bulls, those did not correlate overall throughout their lives (1.3?14.3 years old), but did correlate significantly in two sires. From these results, we conclude that MDCN and MC of frozen spermatozoa differ among sires, and are negatively correlated with HMMP and sperm motility parameters, probably due to mitochondrial oxidative stress resulted in the presence of ROS, demonstrating that these appear to be useful markers to assess sires’ spermatozoa. It should be noted that the MDCN and MC of bull spermatozoa may not vary overall with the age of the sire, whereas those changes with age in some individuals and may affect sperm motility. en-copyright= kn-copyright= en-aut-name=NguyenHai Thanh en-aut-sei=Nguyen en-aut-mei=Hai Thanh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DoSon Quang en-aut-sei=Do en-aut-mei=Son Quang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiHiroshi en-aut-sei=Kobayashi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FunahashiHiroaki en-aut-sei=Funahashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Okayama Prefectural Center for Animal Husbandry and Research kn-affil= affil-num=4 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Spermatozoa kn-keyword=Spermatozoa en-keyword=Bulls kn-keyword=Bulls en-keyword=Mitochondrial content kn-keyword=Mitochondrial content en-keyword=Motility kn-keyword=Motility en-keyword=Frozen semen kn-keyword=Frozen semen END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=6 article-no= start-page=607 end-page=612 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fine Particulate Matter and Diabetes Prevalence in Okayama, Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Many studies have shown an association between long-term exposure to particulate matter having an aerodynamic diameter of 2.5 μm or less (PM2.5) and diabetes mellitus (DM), but few studies have focused on Asian subjects. We thus examined the association between long-term exposure to PM2.5 and DM prevalence in Okayama City, Japan. We included 76,591 participants who had received basic health checkups in 2006 and 2007. We assigned the census-level modeled PM2.5 data from 2006 and 2007 to each participant and defined DM using treatment status and the blood testing. PM2.5 was associated with DM prevalence, and the prevalence ratio (95% confidence interval) was 1.10 (1.00-1.20) following each interquartile range increase (2.1 μg/m3) in PM2.5. This finding is consistent with previous results and suggests that long-term exposure to PM2.5 is associated with an increased prevalence of DM in Okayama City, Japan, where the PM2.5 level is lower than in other cities in Asian countries. en-copyright= kn-copyright= en-aut-name=TaniYasunari en-aut-sei=Tani en-aut-mei=Yasunari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KashimaSaori en-aut-sei=Kashima en-aut-mei=Saori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakaoSoshi en-aut-sei=Takao en-aut-mei=Soshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Environmental Health Sciences Laboratory, Graduate School of Advanced Science and Engineering, Center for the Planetary Health and Innovation Science, The IDEC Institute, Hiroshima University kn-affil= affil-num=3 en-affil=Center for Innovate Clinical Medicine, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=air pollution kn-keyword=air pollution en-keyword=diabetes mellitus kn-keyword=diabetes mellitus en-keyword=epidemiology kn-keyword=epidemiology en-keyword=glycosylated hemoglobin kn-keyword=glycosylated hemoglobin en-keyword=particulate matter kn-keyword=particulate matter END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=20050930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ミトコンドリアクレアチンキナーゼの多様性 kn-title=Heterogeneity of mitochondrial creatine kinase en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KanemitsuFusae en-aut-sei=Kanemitsu en-aut-mei=Fusae kn-aut-name=金光房江 kn-aut-sei=金光 kn-aut-mei=房江 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=20051231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Tim44の遺伝子導入は、ミトコンドリア由来の活性酸素を減少させ、バルーン障害後の糖尿病ラット頚動脈肥厚を抑制する kn-title=Gene delivery of Tim44 reduces mitochondrial superoxide production and ameliorates neointimal proliferation of injured carotid artery in diabetic rats en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsuokaTakashi en-aut-sei=Matsuoka en-aut-mei=Takashi kn-aut-name=松岡孝至 kn-aut-sei=松岡 kn-aut-mei=孝至 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=15 article-no= start-page=5028 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230731 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Methods: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. Results: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. Conclusions: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia. en-copyright= kn-copyright= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoMegumi en-aut-sei=Kondo en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HirohataSatoshi en-aut-sei=Hirohata en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=glycolysis kn-keyword=glycolysis en-keyword=mitochondrial respiration kn-keyword=mitochondrial respiration en-keyword=pulmonary arterial hypertension kn-keyword=pulmonary arterial hypertension en-keyword=pulmonary artery smooth muscle cells kn-keyword=pulmonary artery smooth muscle cells en-keyword=Seahorse technology kn-keyword=Seahorse technology en-keyword=hypoxia kn-keyword=hypoxia en-keyword=ATP production kn-keyword=ATP production END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=4 article-no= start-page=894 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230406 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson's Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson's disease (PD) is characterized by motor symptoms based on a loss of nigrostriatal dopaminergic neurons and by non-motor symptoms which precede motor symptoms. Neurodegeneration accompanied by an accumulation of alpha-synuclein is thought to propagate from the enteric nervous system to the central nervous system. The pathogenesis in sporadic PD remains unknown. However, many reports indicate various etiological factors, such as oxidative stress, inflammation, alpha-synuclein toxicity and mitochondrial impairment, drive neurodegeneration. Exposure to heavy metals contributes to these etiopathogenesis and increases the risk of developing PD. Metallothioneins (MTs) are cysteine-rich metal-binding proteins; MTs chelate metals and inhibit metal-induced oxidative stress, inflammation and mitochondrial dysfunction. In addition, MTs possess antioxidative properties by scavenging free radicals and exert anti-inflammatory effects by suppression of microglial activation. Furthermore, MTs recently received attention as a potential target for attenuating metal-induced alpha-synuclein aggregation. In this article, we summarize MTs expression in the central and enteric nervous system, and review protective functions of MTs against etiopathogenesis in PD. We also discuss neuroprotective strategies for the prevention of central dopaminergic and enteric neurodegeneration by targeting MTs. This review highlights multifunctional MTs as a target for the development of disease-modifying drugs for PD. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=metallothionein kn-keyword=metallothionein en-keyword=Parkinson's disease kn-keyword=Parkinson's disease en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=antioxidant kn-keyword=antioxidant en-keyword=metal kn-keyword=metal en-keyword=synuclein kn-keyword=synuclein en-keyword=astrocyte kn-keyword=astrocyte en-keyword=enteric glial cell kn-keyword=enteric glial cell END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=4 article-no= start-page=e1010732 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overexpression profiling reveals cellular requirements in the context of genetic backgrounds and environments en-subtitle= kn-subtitle= en-abstract= kn-abstract=Overexpression can help life adapt to stressful environments, making an examination of overexpressed genes valuable for understanding stress tolerance mechanisms. However, a systematic study of genes whose overexpression is functionally adaptive (GOFAs) under stress has yet to be conducted. We developed a new overexpression profiling method and systematically identified GOFAs in Saccharomyces cerevisiae under stress (heat, salt, and oxidative). Our results show that adaptive overexpression compensates for deficiencies and increases fitness under stress, like calcium under salt stress. We also investigated the impact of different genetic backgrounds on GOFAs, which varied among three S. cerevisiae strains reflecting differing calcium and potassium requirements for salt stress tolerance. Our study of a knockout collection also suggested that calcium prevents mitochondrial outbursts under salt stress. Mitochondria-enhancing GOFAs were only adaptive when adequate calcium was available and non-adaptive when calcium was deficient, supporting this idea. Our findings indicate that adaptive overexpression meets the cell's needs for maximizing the organism's adaptive capacity in the given environment and genetic context. Author summaryThe study aimed to investigate how overexpression of genes can aid organisms in adapting to stress. The researchers utilized a new method to identify genes in yeast that demonstrated functional adaptability when overexpressed under stress such as heat, salt, and oxidative stress. The results indicated that overexpressing specific genes, like calcium, during salt stress could counteract deficiencies and improve the organism's ability to withstand stress. The study also examined the effect of different genetic backgrounds on these genes and discovered that the impact differed among various yeast strains. Additionally, the study revealed that calcium could play a key role in adapting to salt stress by preventing mitochondrial outbursts. These findings suggest that overexpressing certain genes can help the organism maximize its adaptability to stress in a given environment and genetic context. en-copyright= kn-copyright= en-aut-name=SaekiNozomu en-aut-sei=Saeki en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoChie en-aut-sei=Yamamoto en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EguchiYuichi en-aut-sei=Eguchi en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekitoTakayuki en-aut-sei=Sekito en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShigenobuShuji en-aut-sei=Shigenobu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimuraMami en-aut-sei=Yoshimura en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YashirodaYoko en-aut-sei=Yashiroda en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BooneCharles en-aut-sei=Boone en-aut-mei=Charles kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriyaHisao en-aut-sei=Moriya en-aut-mei=Hisao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Biomedical Business Center, RICOH Futures BU kn-affil= affil-num=4 en-affil=Graduate School of Agriculture, Ehime University kn-affil= affil-num=5 en-affil=National Institute for Basic Biology kn-affil= affil-num=6 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=7 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=8 en-affil=RIKEN Center for Sustainable Resource Science kn-affil= affil-num=9 en-affil=Faculty of Environmental, Life, Natural Science and Technology, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=2 article-no= start-page=73 end-page=75 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2021 Incentive Award of the Okayama Medical Association in Cancer Research (2021 Hayashibara Prize and Yamada Prize) kn-title=令和3年度岡山医学会賞 がん研究奨励賞(林原賞・山田賞) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name=西田充香子 kn-aut-sei=西田 kn-aut-mei=充香子 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科 免疫学 END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=8 article-no= start-page=e0273330 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220818 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intraspecies variation of the mitochondrial genome: An evaluation for phylogenetic approaches based on the conventional choices of genes and segments on mitogenome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intraspecies nucleotide sequence variation is a key to understanding the evolutionary history of a species, such as the geographic distribution and population structure. To date, numerous phylogenetic and population genetics studies have been conducted based on the sequences of a gene or an intergenic region on the mitochondrial genome (mtDNA), such as cytochrome c oxidase subunits or the D-loop. To evaluate the credibility of the usage of such 'classic' markers, we compared the phylogenetic inferences based on the analyses of the partial and entire mtDNA sequences. Importantly, the phylogenetic reconstruction based on the short marker sequences did not necessarily reproduce the tree topologies based on the analyses of the entire mtDNA. In addition, analyses on the datasets of various organisms revealed that the analyses based on the classic markers yielded phylogenetic trees with poor confidence in all tested cases compared to the results based on full-length mtDNA. These results demonstrated that phylogenetic analyses based on complete mtDNA sequences yield more insightful results compared to those based on mitochondrial genes and segments. To ameliorate the shortcomings of the classic markers, we identified a segment of mtDNA that may be used as an 'approximate marker' to closely reproduce the phylogenetic inference obtained from the entire mtDNA in the case of mammalian species, which can be utilized to design amplicon-seq-based studies. Our study demonstrates the importance of the choice of mitochondrial markers for phylogenetic analyses and proposes a novel approach to choosing appropriate markers for mammalian mtDNA that reproduces the phylogenetic inferences obtained from full-length mtDNA. en-copyright= kn-copyright= en-aut-name=Mor?n-L?pezJes?s en-aut-sei=Mor?n-L?pez en-aut-mei=Jes?s kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=VergaraKaren en-aut-sei=Vergara en-aut-mei=Karen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoMasanao en-aut-sei=Sato en-aut-mei=Masanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GajardoGonzalo en-aut-sei=Gajardo en-aut-mei=Gonzalo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UekiShoko en-aut-sei=Ueki en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= affil-num=2 en-affil=Laboratorio de Gen?tica, Acuicultura & Biodiversidad, Departamento de Ciencias Biol?gicas y Biodiversidad, Universidad de Los Lagos kn-affil= affil-num=3 en-affil=Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University kn-affil= affil-num=4 en-affil=Laboratorio de Gen?tica, Acuicultura & Biodiversidad, Departamento de Ciencias Biol?gicas y Biodiversidad, Universidad de Los Lagos kn-affil= affil-num=5 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=5 article-no= start-page=503 end-page=510 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Viral Sequences Are Repurposed for Controlling Antiviral Responses as Non-Retroviral Endogenous Viral Elements en-subtitle= kn-subtitle= en-abstract= kn-abstract=Eukaryotic genomes contain numerous copies of endogenous viral elements (EVEs), most of which are considered endogenous retrovirus (ERV) sequences. Over the past decade, non-retroviral endogenous viral elements (nrEVEs) derived from ancient RNA viruses have been discovered. Several functions have been proposed for these elements, including antiviral defense. This review summarizes the current understanding of nrEVEs derived from RNA viruses, particularly endogenous bornavirus-like elements (EBLs) and endogenous filovirus-like elements (EFLs). EBLs are one of the most extensively studied nrEVEs. The EBL derived from bornavirus nucleoprotein (EBLN) is thought to function as a non-coding RNA or protein that regulates host gene expression or inhibits virus propagation. Ebolavirus and marburgvirus, which are filoviruses, induce severe hemorrhagic fever in humans and nonhuman primates. Although the ecology of filoviruses remains unclear, bats are believed to be potential reservoirs. Based on the knowledge from EBLs, it is postulated that EFLs in the bat genome help to maintain the balance between filovirus infection and the bat’s defense system, which may partially explain why bats act as potential reservoirs. Further research into the functions of nrEVEs could reveal novel antiviral systems and inspire novel antiviral approaches. en-copyright= kn-copyright= en-aut-name=OgawaHirohito en-aut-sei=Ogawa en-aut-mei=Hirohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HondaTomoyuki en-aut-sei=Honda en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=EVE kn-keyword=EVE en-keyword=nrEVE kn-keyword=nrEVE en-keyword=bornavirus kn-keyword=bornavirus en-keyword=filovirus kn-keyword=filovirus en-keyword=antiviral kn-keyword=antiviral END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=4 article-no= start-page=415 end-page=421 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=5-Nitro-2-(3-phenylpropylamino) Benzoic Acid Inhibits the Proliferation and Migration of Lens Epithelial Cells by Blocking CaMKII Signaling en-subtitle= kn-subtitle= en-abstract= kn-abstract=Posterior capsule opacification (PCO) is a post-surgery complication of cataract surgery, and lens epithelial cells (LECs) are involved in its development. A suppressive effect on LECs is exerted by the non specific chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) exerts. Herein, the growth and migration inhibitory effects of NPPB on LECs were assessed, and the mechanism underlying the effects were investigated by focusing on Ca2+/CaMKII signaling. LECs were treated with different concentrations of NPPB, and the changes in cell viability, cell-cycle distribution, anchorage-dependent growth, migration, Ca2+ level, and CaMKII expression were evaluated. NPPB inhibited LECs’ proliferation and induced G1 cell-cycle arrest in the cells. Regarding LECs’ mobility, NPPB suppressed the cells’ anchorage-dependent growth ability and inhibited their migration. Changes in cell phenotypes were associated with an increased intracellular Ca2+ level and down-regulation of CaMKII. Together these results confirmed the inhibitory effect of NPPB on the proliferation and migration of LECs, and the effect was shown to be associated with the induced level of Ca2+ and the inhibition of CaMKII signaling transduction. en-copyright= kn-copyright= en-aut-name=KangHaijun en-aut-sei=Kang en-aut-mei=Haijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HuangDongmei en-aut-sei=Huang en-aut-mei=Dongmei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KangGangjin en-aut-sei=Kang en-aut-mei=Gangjin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YangXu en-aut-sei=Yang en-aut-mei=Xu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiHeng en-aut-sei=Li en-aut-mei=Heng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LiuSiyuan en-aut-sei=Liu en-aut-mei=Siyuan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GouWenjun en-aut-sei=Gou en-aut-mei=Wenjun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiuLinglin en-aut-sei=Liu en-aut-mei=Linglin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=QiuYuyan en-aut-sei=Qiu en-aut-mei=Yuyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Suining Central Hospital kn-affil= affil-num=2 en-affil=Department of Cardiovascular, Suining Central Hospital kn-affil= affil-num=3 en-affil=Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Suining Central Hospital kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Suining Central Hospital kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Suining Central Hospital kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Suining Central Hospital kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Suining Central Hospital kn-affil= affil-num=9 en-affil=Department of Ophthalmology, Suining Central Hospital kn-affil= en-keyword=5-nitro-2-(3-phenylpropylamino) benzoic acid kn-keyword=5-nitro-2-(3-phenylpropylamino) benzoic acid en-keyword=CaMKII kn-keyword=CaMKII en-keyword=lens epithelial cell kn-keyword=lens epithelial cell en-keyword=migration kn-keyword=migration en-keyword=proliferation kn-keyword=proliferation END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=14 article-no= start-page=7856 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220716 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Muscle Fiber Composition Changes after Selective Nerve Innervation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Facial nerve paralysis interferes with mimetic muscle function. To reconstruct natural facial movement, free muscle flaps are transplanted as new muscles. However, it is difficult to maintain resting tonus. A dual innervation technique in which other nerves such as the hypoglossal nerve or contralateral facial nerve are added is often applied. Using 10-week-old rats (n = 10), the masseteric and hypoglossal nerves were cut, and the distal stump of the masseteric nerve and the proximal stump of the hypoglossal nerve were then sutured (suture group). In the other group, the masseteric nerve was cut and cauterized (cut group). Immunohistochemistry and microarray were performed on the extracted masseter muscle. The immunohistochemistry results suggested that the muscles in the suture group obtained oxidative characteristics. The microarray showed the genes involved in mitochondrial function, including Perm1. In summary, our data support the validity of the dualinnervation technique for facial paralysis treatment. en-copyright= kn-copyright= en-aut-name=WatanabeShiho en-aut-sei=Watanabe en-aut-mei=Shiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OchiaiHiroko en-aut-sei=Ochiai en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakumaHisashi en-aut-sei=Sakuma en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriTaisuke en-aut-sei=Mori en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YazawaMasaki en-aut-sei=Yazawa en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkaAiko en-aut-sei=Oka en-aut-mei=Aiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KishiKazuo en-aut-sei=Kishi en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Plastic and Reconstructive Surgery, Okayama University Hospital, kn-affil= affil-num=2 en-affil=Laboratory of Regenerative Medicine, Department of Plastic and Reconstructive Surgery, Division of Hearing and Balance Disorder, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center kn-affil= affil-num=3 en-affil=Department of Plastic and Reconstructive Surgery, Tokyo Dental College Ichikawa General Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, National Cancer Center Research Institute kn-affil= affil-num=5 en-affil=Department of Plastic and Reconstructive Surgery, Keio University School of Medicine kn-affil= affil-num=6 en-affil=Laboratory of Regenerative Medicine, Department of Plastic and Reconstructive Surgery, Division of Hearing and Balance Disorder, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center kn-affil= affil-num=7 en-affil=Department of Plastic and Reconstructive Surgery, Keio University School of Medicine kn-affil= en-keyword=muscle fiber type kn-keyword=muscle fiber type en-keyword=facial paralysis kn-keyword=facial paralysis en-keyword=dualinnervation kn-keyword=dualinnervation en-keyword=masseter muscle kn-keyword=masseter muscle END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue= article-no= start-page=864225 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220629 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nutrient Condition in the Microenvironment Determines Essential Metabolisms of CD8(+) T Cells for Enhanced IFN gamma Production by Metformin en-subtitle= kn-subtitle= en-abstract= kn-abstract=Metformin (Met), a first-line drug for type 2 diabetes, lowers blood glucose levels by suppressing gluconeogenesis in the liver, presumably through the liver kinase B1-dependent activation of AMP-activated protein kinase (AMPK) after inhibiting respiratory chain complex I. Met is also implicated as a drug to be repurposed for cancers; its mechanism is believed identical to that of gluconeogenesis inhibition. However, AMPK activation requires high Met concentrations at more than 1 mM, which are unachievable in vivo. The immune-mediated antitumor response might be the case in a low dose Met. Thus, we proposed activating or expanding tumor-infiltrating CD8(+) T cells (CD8TILs) in a mouse model by orally administering Met in free drinking water. Here we showed that Met, at around 10 mu M and a physiologically relevant concentration, enhanced production of IFN gamma,TNF alpha and expression of CD25 of CD8(+) T cells upon TCR stimulation. Under a glucose-rich condition, glycolysis was exclusively involved in enhancing IFN gamma production. Under a low-glucose condition, fatty acid oxidation or autophagy-dependent glutaminolysis, or both, was also involved. Moreover, phosphoenolpyruvate carboxykinase 1 (PCK1), converting oxaloacetate to phosphoenolpyruvate, became essential. Importantly, the enhanced IFN gamma production was blocked by a mitochondrial ROS scavenger and not by an inhibitor of AMPK. In addition, IFN gamma production by CD8TILs relied on pyruvate translocation to the mitochondria and PCK1. Our results revealed a direct effect of Met on IFN gamma production of CD8(+) T cells that was dependent on differential metabolic pathways and determined by nutrient conditions in the microenvironment. en-copyright= kn-copyright= en-aut-name=ChaoRuoyu en-aut-sei=Chao en-aut-mei=Ruoyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaNahoko en-aut-sei=Yamashita en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TokumasuMiho en-aut-sei=Tokumasu en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ZhaoWeiyang en-aut-sei=Zhao en-aut-mei=Weiyang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KudoIkuru en-aut-sei=Kudo en-aut-mei=Ikuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=CD8+T lymphocytes kn-keyword=CD8+T lymphocytes en-keyword=glycolysis kn-keyword=glycolysis en-keyword=FAO kn-keyword=FAO en-keyword=glutaminolysis kn-keyword=glutaminolysis en-keyword=IFNg kn-keyword=IFNg en-keyword=autophagy plus T kn-keyword=autophagy plus T en-keyword=metformin kn-keyword=metformin END start-ver=1.4 cd-journal=joma no-vol=1866 cd-vols= no-issue=8 article-no= start-page=130171 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metformin-ROS-Nrf2 connection in the host defense mechanism against oxidative stress, apoptosis, cancers, and ageing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reactive oxygen species (ROS) acts as a second messenger to trigger biological responses in low concentrations, while it is implicated to be toxic to biomolecules in high concentrations. Mild inhibition of respiratory chain Complex I by metformin at physiologically relevant concentrations stimulates production of low-level mitochondrial ROS. The ROS seems to induce anti-oxidative stress response via activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase (GPx), which results in not only elimination of ROS but also activation of cellular responses including resistance to apoptosis, metabolic changes, cell proliferation, senescence prevention, lifespan extension, and immune T cell activation against cancers, regardless of its effect controlling blood glucose level and T2DM. Although metformin's effect against T2DM, cancers, and ageing, are believed mostly attributed to the activation of AMP-activated protein kinase (AMPK), the cellular responses involving metformin-ROS-Nrf2 axis might be another natural asset to improve healthspan and lifespan. en-copyright= kn-copyright= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishidaMikako en-aut-sei=Nishida en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Mitochondrial ROS kn-keyword=Mitochondrial ROS en-keyword=Oxidative stress kn-keyword=Oxidative stress en-keyword=Apoptosis kn-keyword=Apoptosis en-keyword=Ageing kn-keyword=Ageing en-keyword=Nrf2 kn-keyword=Nrf2 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=3 article-no= start-page=235 end-page=245 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Roles of Transmembrane Protein 97 (TMEM97) in Adipose Tissue and Skeletal Muscle en-subtitle= kn-subtitle= en-abstract= kn-abstract=The combination of sarcopenia and obesity (sarcopenic obesity) is associated with the development of metabolic syndrome and cardiovascular events. The molecular pathways that develop sarcopenic obesity have studied intensively. Transmembrane protein 97 (TMEM97) is 176 amino acids conserved integral membrane protein with four transmembrane domains that is expressed in several types of cancer. Its physiological significance in adipose tissue and skeletal muscle has been unclear. We studied TMEM97-transgenic mice and mice lacking TMEM97, and our findings indicate that TMEM97 expression is regulated in adipose tissue and skeletal muscle from obesity. TMEM97 represses adipogenesis and promotes myogenesis in vitro. Fat-specific TMEM97 transgenic mice showed systemic insulin resistance. Mice overexpressing TMEM97 in skeletal muscle exhibited systemic insulin resistance. Mice lacking TMEM97 were protected against diet-induced obesity and insulin resistance. These phenotypes are associated with the effects of TMEM97 on inflammation genes in adipose tissue and skeletal muscle. Our findings indicates that there is a link between TMEM97 and chronic inflammation in obesity. en-copyright= kn-copyright= en-aut-name=TentaMasafumi en-aut-sei=Tenta en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=adipose tissue kn-keyword=adipose tissue en-keyword=skeletal muscle kn-keyword=skeletal muscle en-keyword=obesity kn-keyword=obesity END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=4930 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220323 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=LCZ696 ameliorates doxorubicin-induced cardiomyocyte toxicity in rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main bottleneck for its clinical application. In this study, we investigated the potential benefit of LCZ696, an angiotensin receptor-neprilysin inhibitor against DOX-induced cardiotoxicity in rats and H9c2 cells and determined whether the mechanism underlying any such effects involves its antioxidant activity. Male Sprague-Dawley rats were randomly separated into four groups, each consisting of 15 rats (DOX (1.5 mg/kg/day intraperitoneally for 10 days followed by non-treatment for 8 days); DOX + valsartan (31 mg/kg/day by gavage from day 1 to day 18); DOX + LCZ696 (68 mg/kg/day by gavage from day 1 to day 18); and control (saline intraperitoneally for 10 days). DOX-induced elevation of cardiac troponin T levels on day 18 was significantly reduced by LCZ696, but not valsartan. The DOX-induced increase in myocardial reactive oxygen species (ROS) levels determined using dihydroethidium was significantly ameliorated by LCZ696, but not valsartan, and was accompanied by the suppression of DOX-induced increase in p47phox. LCZ696 recovered the DOX-induced decrease in phosphorylation of adenosine monophosphate-activated protein kinase and increased the ratio of Bax and Bcl-2. In H9c2 cardiomyocytes, LCZ696 reduced DOX-induced mitochondrial ROS generation and improved cell viability more than valsartan. Our findings indicated that LCZ696 ameliorated DOX-induced cardiotoxicity in rat hearts in vivo and in vitro, possibly by mediating a decrease in oxidative stress. en-copyright= kn-copyright= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AmiokaNaofumi en-aut-sei=Amioka en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HatipogluOmer F. en-aut-sei=Hatipoglu en-aut-mei=Omer F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YonezawaTomoko en-aut-sei=Yonezawa en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacology, Kindai University kn-affil= affil-num=5 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=7 article-no= start-page=3587 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus en-subtitle= kn-subtitle= en-abstract= kn-abstract=There is a close relationship between diabetes mellitus and heart failure, and diabetes is an independent risk factor for heart failure. Diabetes and heart failure are linked by not only the complication of ischemic heart disease, but also by metabolic disorders such as glucose toxicity and lipotoxicity based on insulin resistance. Cardiac dysfunction in the absence of coronary artery disease, hypertension, and valvular disease is called diabetic cardiomyopathy. Diabetes-induced hyperglycemia and hyperinsulinemia lead to capillary damage, myocardial fibrosis, and myocardial hypertrophy with mitochondrial dysfunction. Lipotoxicity with extensive fat deposits or lipid droplets is observed on cardiomyocytes. Furthermore, increased oxidative stress and inflammation cause cardiac fibrosis and hypertrophy. Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor is currently one of the most effective treatments for heart failure associated with diabetes. However, an effective treatment for lipotoxicity of the myocardium has not yet been established, and the establishment of an effective treatment is needed in the future. This review provides an overview of heart failure in diabetic patients for the clinical practice of clinicians. en-copyright= kn-copyright= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AkagiSatoshi en-aut-sei=Akagi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoYukihiro en-aut-sei=Saito en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EjiriKentaro en-aut-sei=Ejiri en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuoNaoaki en-aut-sei=Matsuo en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IchikawaKeishi en-aut-sei=Ichikawa en-aut-mei=Keishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IwasakiKeiichiro en-aut-sei=Iwasaki en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NaitoTakanori en-aut-sei=Naito en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NambaYusuke en-aut-sei=Namba en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YoshidaMasatoki en-aut-sei=Yoshida en-aut-mei=Masatoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SugiyamaHiroki en-aut-sei=Sugiyama en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=heart failure kn-keyword=heart failure en-keyword=lipotoxicity kn-keyword=lipotoxicity en-keyword=SGLT2 inhibitor kn-keyword=SGLT2 inhibitor END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=19 article-no= start-page=10776 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211005 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PARN-like Proteins Regulate Gene Expression in Land Plant Mitochondria by Modulating mRNA Polyadenylation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mitochondria have their own double-stranded DNA genomes and systems to regulate transcription, mRNA processing, and translation. These systems differ from those operating in the host cell, and among eukaryotes. In recent decades, studies have revealed several plant-specific features of mitochondrial gene regulation. The polyadenylation status of mRNA is critical for its stability and translation in mitochondria. In this short review, I focus on recent advances in understanding the mechanisms regulating mRNA polyadenylation in plant mitochondria, including the role of poly(A)-specific ribonuclease-like proteins (PARNs). Accumulating evidence suggests that plant mitochondria have unique regulatory systems for mRNA poly(A) status and that PARNs play pivotal roles in these systems. en-copyright= kn-copyright= en-aut-name=HirayamaTakashi en-aut-sei=Hirayama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Institute of Plant Science and Resources, Okayama University kn-affil= en-keyword=mitochondria kn-keyword=mitochondria en-keyword=polyadenylation kn-keyword=polyadenylation en-keyword=poly(A)-specific ribonuclease kn-keyword=poly(A)-specific ribonuclease END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210924 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=酸化ストレスにおけるミトコンドリア機能、カルシウム放出、ROS生成におけるTRPM4チャネルの役割 kn-title=Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name=王晨 kn-aut-sei=王 kn-aut-mei=晨 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil=岡山大学大学院医歯薬学総合研究科 END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=101404 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Production of TRPM4 knockout cell line using rat cardiomyocyte H9c2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The method presented in this article are related to the research article entitled as "Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress" [1]. TRPM4, a non-selective monovalent cation channel, is not only involved in the generation of the action potential in cardiomyocytes, but also thought to be a key molecule in the development of the ischemia-reperfusion injury of the brain and the heart [2-5]. However, existing pharmacological inhibitors for the TRPM4 channel have problems of non-specificity [6]. This article describes methods used for targeted genomic deletion in the rat cardiomyocyte H9c2 using the CRISPR-Cas9 genome editing system in order to suppress TRPM4 protein expression. Confocal microscopy, flow cytometry, Sanger sequencing, and western blotting are performed to confirm vector transfection and the subsequent knockout of the TRPM4 protein. These data provide information on the comprehensive analyses for knocking out the rat TRPM4 channel using CRISPR/Cas9. The analyses include confocal microscopy, flow cytometry, Sanger sequencing, and western blotting. This dataset will benefit biological and medical researchers studying the function of TRPM4-expressing cells including neurons, cardiomyocytes, and vascular endothelial cells. It is also useful to study the involvement of the TRPM4 channel in pathological processes such as cardiac arrhythmia and ischemia-reperfusion injury. The dataset can be used to guide the experiment of knocking out the TRPM4 gene and its subsequent application to the study of disease process caused by the gene. en-copyright= kn-copyright= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MaedaMasakazu en-aut-sei=Maeda en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ChenJian en-aut-sei=Chen en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangMengxue en-aut-sei=Wang en-aut-mei=Mengxue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medicine, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=TRPM4 kn-keyword=TRPM4 en-keyword=Cardiomyocyte kn-keyword=Cardiomyocyte en-keyword=H9c2 kn-keyword=H9c2 en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=Confocal microscopy kn-keyword=Confocal microscopy en-keyword=DNA sequencing kn-keyword=DNA sequencing en-keyword=Flow cytometry kn-keyword=Flow cytometry en-keyword=Western blotting kn-keyword=Western blotting END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=14936 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210722 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Photocontrolled apoptosis induction using precursor miR-664a and an RNA carrier-conjugated with photosensitizer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Methods to spatially induce apoptosis are useful for cancer therapy. To control the induction of apoptosis, methods using light, such as photochemical internalization (PCI), have been developed. We hypothesized that photoinduced delivery of microRNAs (miRNAs) that regulate apoptosis could spatially induce apoptosis. In this study, we identified pre-miR-664a as a novel apoptosis-inducing miRNA via mitochondrial apoptotic pathway. Further, we demonstrated the utility of photoinduced cytosolic dispersion of RNA (PCDR), which is an intracellular RNA delivery method based on PCI. Indeed, apoptosis is spatially regulated by pre-miR-664a and PCDR. In addition, we found that apoptosis induced by pre-miR-664a delivered by PCDR was more rapid than that by lipofection. These results suggest that pre-miR-664a is a nucleic acid drug candidate for cancer therapy and PCDR and pre-miR-664a-based strategies have potential therapeutic uses for diseases affecting various cell types. en-copyright= kn-copyright= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NawachiTomoko en-aut-sei=Nawachi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkutaniRuriko en-aut-sei=Okutani en-aut-mei=Ruriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Department of Biomedical Engineering, Faculty of Engineering, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=566 cd-vols= no-issue= article-no= start-page=190 end-page=196 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021820 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ischemic heart disease is one of the most common causes of death worldwide. Mitochondrial dysfunction, excessive reactive oxygen species (ROS) generation, and calcium (Ca2?) overload are three key factors leading to myocardial death during ischemia-reperfusion (I/R) injury. Inhibition of TRPM4, a Ca2?-activated nonselective cation channel, protects the rat heart from I/R injury, but the specific mechanism underlying this effect is unclear. In this study, we investigated the mechanism of cardioprotection against I/R injury via TRPM4 using hydrogen peroxide (H2O2), a major contributor to oxidative stress, as an I/R injury model. We knocked out the TRPM4 gene in the rat cardiomyocyte cell line H9c2 using CRISPR/Cas9. Upon H2O2 treatment, intracellular Ca2? level and ROS production increased in wild type (WT) cells but not in TRPM4 knockout (TRPM4KO) cells. With this treatment, two indicators of mitochondrial function, mitochondrial membrane potential (DJm) and intracellular ATP levels, decreased inWT but not in TRPM4KO cells. Taken together, these findings suggest that blockade of the TRPM4 channel might protect the myocardium from oxidative stress by maintaining the mitochondrial membrane potential and intracellular ATP levels, possibly through preventing aberrant increases in intracellular Ca2? and ROS. en-copyright= kn-copyright= en-aut-name=WangChen en-aut-sei=Wang en-aut-mei=Chen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenJian en-aut-sei=Chen en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangMengxue en-aut-sei=Wang en-aut-mei=Mengxue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NaruseKeiji en-aut-sei=Naruse en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakahashiKen en-aut-sei=Takahashi en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=3 article-no= start-page=363 end-page=372 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of the Transcription Factor BTB and CNC Homology 1 in a Rat Model of Acute Liver Injury Induced by Experimental Endotoxemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hepatic oxidative stress plays an important role in the pathogenesis of several acute liver diseases, and free heme is thought to contribute to endotoxemia-induced acute liver injury. The heme oxygenase 1 (HO-1) gene is upregulated and the δ-aminolevulinate synthase (ALAS1) gene is downregulated in the rat liver following lipopolysaccharide (LPS) treatment. BTB and CNC homology 1 (Bach1) is a heme-responsive transcription factor that normally represses HO-1 expression. In this study, we evaluated the changes in HO-1, ALAS1, and Bach1 expression and nuclear Bach1 expression in rat livers following intravenous LPS administration (10 mg/kg body weight). LPS significantly upregulated HO-1 mRNA and downregulated ALAS1 mRNA in the rat livers, suggesting that hepatic free heme concentrations are increased after LPS treatment. Bach1 mRNA was strongly induced after LPS injection. In contrast, nuclear Bach1 was significantly but transiently decreased after LPS treatment. Rats were also administered hemin (50 mg/kg body weight) intravenously to elevate heme concentrations, which decreased nuclear Bach1 levels. Our results suggest that elevated hepatic free heme may be associated with a decline of nuclear Bach1, and induction of Bach1 mRNA may compensate for the decreased nuclear Bach1 after LPS treatment in the rat liver. en-copyright= kn-copyright= en-aut-name=TaniokaNohito en-aut-sei=Tanioka en-aut-mei=Nohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoriEmiko en-aut-sei=Omori en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaokaMasakazu en-aut-sei=Yamaoka en-aut-mei=Masakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Faculty of Health and Welfare Science, Okayama Prefectural University kn-affil= affil-num=5 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=heme oxygenase-1 kn-keyword=heme oxygenase-1 en-keyword=BTB and CNC homology 1 kn-keyword=BTB and CNC homology 1 en-keyword= heme, kn-keyword= heme, en-keyword=lipopolysaccharide kn-keyword=lipopolysaccharide en-keyword= liver injury kn-keyword= liver injury END start-ver=1.4 cd-journal=joma no-vol=75 cd-vols= no-issue=2 article-no= start-page=153 end-page=167 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lactoferrin-like Immunoreactivity in Distinct Neuronal Populations in the Mouse Central Nervous System en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lactoferrin (Lf) is an iron-binding glycoprotein mainly found in exocrine secretions and the secondary granules of neutrophils. In the central nervous system (CNS), expression of the Lf protein has been reported in the lesions of some neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as in the aged brain. Lf is primarily considered an iron chelator, protecting cells from potentially toxic iron or iron-requiring microorganisms. Other biological functions of Lf include immunomodulation and transcriptional regulation. However, the roles of Lf in the CNS have yet to be fully clarified. In this study, we raised an antiserum against mouse Lf and investigated the immunohistochemical localization of Lf-like immunoreactivity (Lf-LI) throughout the CNS of adult mice. Lf-LI was found in some neuronal populations throughout the CNS. Intense labeling was found in neurons in the olfactory systems, hypothalamic nuclei, entorhinal cortex, and a variety of brainstem nuclei. This study provides detailed information on the Lf-LI distribution in the CNS, and the findings should promote further understanding of both the physiological and pathological significance of Lf in the CNS. en-copyright= kn-copyright= en-aut-name=ShimaokaShigeyoshi en-aut-sei=Shimaoka en-aut-mei=Shigeyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HamaokaHitomi en-aut-sei=Hamaoka en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueJunji en-aut-sei=Inoue en-aut-mei=Junji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TooyamaIkuo en-aut-sei=Tooyama en-aut-mei=Ikuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KondoYoichi en-aut-sei=Kondo en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical and Pharmaceutical University kn-affil= affil-num=2 en-affil=Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical and Pharmaceutical University kn-affil= affil-num=3 en-affil=Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical and Pharmaceutical University kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Molecular Neuroscience Research Center, Shiga University of Medical Science kn-affil= affil-num=6 en-affil=Molecular Neuroscience Research Center, Shiga University of Medical Science kn-affil= en-keyword=lactoferrin kn-keyword=lactoferrin en-keyword=immunohistochemistry kn-keyword=immunohistochemistry en-keyword=brain mapping kn-keyword=brain mapping END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HMGB1 Translocation in Neurons after Ischemic Insult: Subcellular Localization in Mitochondria and Peroxisomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=High mobility group box-1 (HMGB1), a nonhistone chromatin DNA-binding protein, is released from neurons into the extracellular space under ischemic, hemorrhagic, and traumatic insults. However, the details of the time-dependent translocation of HMGB1 and the subcellular localization of HMGB1 through the release process in neurons remain unclear. In the present study, we examined the subcellular localization of HMGB1 during translocation of HMGB1 in the cytosolic compartment using a middle cerebral artery occlusion and reperfusion model in rats. Double immunofluorescence microscopy revealed that HMGB1 immunoreactivities were colocalized with MTCO1(mitochondrially encoded cytochrome c oxidase I), a marker of mitochondria, and catalase, a marker of peroxisomes, but not with Rab5/Rab7 (RAS-related GTP-binding protein), LC3A/B (microtubule-associated protein 1 light chain 3), KDEL (KDEL amino acid sequence), and LAMP1 (Lysosomal Associated Membrane Protein 1), which are endosome, phagosome, endoplasmic reticulum, and lysosome markers, respectively. Immunoelectron microscopy confirmed that immune-gold particles for HMGB1 were present inside the mitochondria and peroxisomes. Moreover, HMGB1 was found to be colocalized with Drp1 (Dynamin-related protein 1), which is involved in mitochondrial fission. These results revealed the specific subcellular localization of HMGB1 during its release process under ischemic conditions. en-copyright= kn-copyright= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuyasuYusuke en-aut-sei=Fukuyasu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TeshigawaraKiyoshi en-aut-sei=Teshigawara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuLi en-aut-sei=Fu en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Human Morphology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=middle cerebral artery occlusion kn-keyword=middle cerebral artery occlusion en-keyword=high-mobility group box 1 kn-keyword=high-mobility group box 1 en-keyword=subcellular localization and subcellular organelle kn-keyword=subcellular localization and subcellular organelle END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=9 article-no= start-page=3254 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Chronic Systemic Exposure to Low-Dose Rotenone Induced Central and Peripheral Neuropathology and Motor Deficits in Mice: Reproducible Animal Model of Parkinson's Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epidemiological studies demonstrated that pesticide exposure, such as rotenone and paraquat, increases the risk of Parkinson's disease (PD). Chronic systemic exposure to rotenone, a mitochondrial complex I inhibitor, could reproduce many features of PD. However, the adoption of the models is limiting because of variability in animal sensitivity and the inability of other investigators to consistently reproduce the PD neuropathology. In addition, most of rotenone models were produced in rats. Here, we tried to establish a high-reproducible rotenone model using C57BL/6J mice. The rotenone mouse model was produced by chronic systemic exposure to a low dose of rotenone (2.5 mg/kg/day) for 4 weeks by subcutaneous implantation of rotenone-filled osmotic mini pump. The rotenone-treated mice exhibited motor deficits assessed by open field, rotarod and cylinder test and gastrointestinal dysfunction. Rotenone treatment decreased the number of dopaminergic neuronal cells in the substantia nigra pars compacta (SNpc) and lesioned nerve terminal in the striatum. In addition, we observed significant reduction of cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) and the intestinal myenteric plexus. Moreover, alpha-synuclein was accumulated in neuronal soma in the SNpc, DMV and intestinal myenteric plexus in rotenone-treated mice. These data suggest that the low-dose rotenone mouse model could reproduce behavioral and central and peripheral neurodegenerative features of PD and be a useful model for investigation of PD pathogenesis. en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IsookaNami en-aut-sei=Isooka en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ImafukuFuminori en-aut-sei=Imafuku en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SunJin en-aut-sei=Sun en-aut-mei=Jin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikuokaRyo en-aut-sei=Kikuoka en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FurukawaChieko en-aut-sei=Furukawa en-aut-mei=Chieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=rotenone kn-keyword=rotenone en-keyword=Parkinson's disease kn-keyword=Parkinson's disease en-keyword=dopaminergic neuron kn-keyword=dopaminergic neuron en-keyword=dorsal motor nucleus of the vagus kn-keyword=dorsal motor nucleus of the vagus en-keyword=myenteric plexus kn-keyword=myenteric plexus en-keyword=neurodegeneration kn-keyword=neurodegeneration en-keyword=α-synuclein kn-keyword=α-synuclein en-keyword=motor deficit kn-keyword=motor deficit END start-ver=1.4 cd-journal=joma no-vol=G3: Genes Genomes Genetics cd-vols= no-issue=1 article-no= start-page=217 end-page=228 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Medaka Population Genome Structure and Demographic History Described via Genotyping-by-Sequencing en-subtitle= kn-subtitle= en-abstract= kn-abstract=Medaka is a model organism in medicine, genetics, developmental biology and population genetics. Lab stocks composed of more than 100 local wild populations are available for research in these fields. Thus, medaka represents a potentially excellent bioresource for screening disease-risk- and adaptation-related genes in genome-wide association studies. Although the genetic population structure should be known before performing such an analysis, a comprehensive study on the genome-wide diversity of wild medaka populations has not been performed. Here, we performed genotyping-by-sequencing (GBS) for 81 and 12 medakas captured from a bioresource and the wild, respectively. Based on the GBS data, we evaluated the genetic population structure and estimated the demographic parameters using an approximate Bayesian computation (ABC) framework. The genome-wide data confirmed that there were substantial differences between local populations and supported our previously proposed hypothesis on medaka dispersal based on mitochondrial genome (mtDNA) data. A new finding was that a local group that was thought to be a hybrid between the northern and the southern Japanese groups was actually an origin of the northern Japanese group. Thus, this paper presents the first population-genomic study of medaka and reveals its population structure and history based on chromosomal genetic diversity. en-copyright= kn-copyright= en-aut-name=KatsumuraTakafumi en-aut-sei=Katsumura en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaShoji en-aut-sei=Oda en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MitaniHiroshi en-aut-sei=Mitani en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OotaHiroki en-aut-sei=Oota en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=2 en-affil=Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo kn-affil= affil-num=3 en-affil=Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo kn-affil= affil-num=4 en-affil=Department of Anatomy, Kitasato University School of Medicine kn-affil= en-keyword=local population kn-keyword=local population en-keyword=freshwater fish kn-keyword=freshwater fish en-keyword=demography kn-keyword=demography en-keyword=RAD-seq kn-keyword=RAD-seq en-keyword=bioresource kn-keyword=bioresource END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=6 article-no= start-page=1974 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200313 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevention of Cognitive Decline in Alzheimer's Disease by Novel Antioxidative Supplements en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oxidative stress plays a crucial role in Alzheimer's disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid beta (A beta) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative stress plays a major role in AD, oxidative stress has been considered as a therapeutic target of AD. In spite of favorable preclinical study outcomes, previous antioxidative components, including a single antioxidative supplement such as vitamin C, vitamin E or their mixtures, did not clearly show any therapeutic effect on cognitive decline in AD. However, novel antioxidative supplements can be beneficial for AD patients. In this review, we summarize the interplay between oxidative stress and the A beta cascade, and introduce novel antioxidative supplements expected to prevent cognitive decline in AD. en-copyright= kn-copyright= en-aut-name=TadokoroKoh en-aut-sei=Tadokoro en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InufusaHaruhiko en-aut-sei=Inufusa en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=LoonAlan Foo Nyuk en-aut-sei=Loon en-aut-mei=Alan Foo Nyuk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Division of Anti-Oxidant Research, Life Science Research Center, Gifu University kn-affil= affil-num=4 en-affil=Hovid Berhad kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Alzheimer's disease kn-keyword=Alzheimer's disease en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=supplement kn-keyword=supplement END start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=3 article-no= start-page=470 end-page=480 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191113 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulation of the Poly(A) Status of Mitochondrial mRNA by Poly(A)-Specific Ribonuclease Is Conserved among Land Plants en-subtitle= kn-subtitle= en-abstract= kn-abstract=Regulation of the stability and the quality of mitochondrial RNA is essential for the maintenance of mitochondrial and cellular functions in eukaryotes. We have previously reported that the eukaryotic poly(A)-specific ribonuclease (PARN) and the prokaryotic poly(A) polymerase encoded by AHG2 and AGS1, respectively, coordinately regulate the poly(A) status and the stability of mitochondrial mRNA in Arabidopsis. Mitochondrial function of PARN has not been reported in any other eukaryotes. To know how much this PARN-based mitochondrial mRNA regulation is conserved among plants, we studied the AHG2 and AGS1 counterparts of the liverwort, Marchantia polymorpha, a member of basal land plant lineage. We found that M. polymorpha has one ortholog each for AHG2 and AGS1, named MpAHG2 and MpAGS1, respectively. Their Citrine-fused proteins were detected in mitochondria of the liverwort. Molecular genetic analysis showed that MpAHG2 is essential and functionally interacts with MpAGS1 as observed in Arabidopsis. A recombinant MpAHG2 protein had a deadenylase activity in vitro. Overexpression of MpAGS1 and the reduced expression of MpAHG2 caused an accumulation of polyadenylated Mpcox1 mRNA. Furthermore, MpAHG2 suppressed Arabidopsis ahg2-1 mutant phenotype. These results suggest that the PARN-based mitochondrial mRNA regulatory system is conserved in land plants. en-copyright= kn-copyright= en-aut-name=KanazawaMai en-aut-sei=Kanazawa en-aut-mei=Mai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaYoko en-aut-sei=Ikeda en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishihamaRyuichi en-aut-sei=Nishihama en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamaokaShohei en-aut-sei=Yamaoka en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LeeNam-Hee en-aut-sei=Lee en-aut-mei=Nam-Hee kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamatoKatsuyuki T en-aut-sei=Yamato en-aut-mei=Katsuyuki T kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KohchiTakayuk en-aut-sei=Kohchi en-aut-mei=Takayuk kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HirayamaTakashi en-aut-sei=Hirayama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Division of Science for Bioresources, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Division of Science for Bioresources, Graduate School of Environment and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Biostudies, Kyoto University kn-affil= affil-num=4 en-affil=Graduate School of Biostudies, Kyoto University kn-affil= affil-num=5 en-affil=Department of Life Sciences, Faculty of Science and Engineering, Sorbonne University kn-affil= affil-num=6 en-affil=Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kindai University kn-affil= affil-num=7 en-affil=Graduate School of Biostudies, Kyoto University kn-affil= affil-num=8 en-affil=Division of Science for Bioresources, Graduate School of Environment and Life Science, Okayama University kn-affil= en-keyword=Arabidopsis kn-keyword=Arabidopsis en-keyword=Marchantia polymorpha kn-keyword=Marchantia polymorpha en-keyword=Mitochondria kn-keyword=Mitochondria en-keyword= Poly(A) polymerase kn-keyword= Poly(A) polymerase en-keyword=Poly(A) regulation kn-keyword=Poly(A) regulation en-keyword= Poly(A)-specific ribonuclease kn-keyword= Poly(A)-specific ribonuclease END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue= article-no= start-page=42 end-page=56 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20191122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=2-Methylthio Conversion of N6-Isopentenyladenosine in Mitochondrial tRNAs by CDK5RAP1 Promotes the Maintenance of Glioma-Initiating Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=2-Methylthio-N-6-isopentenyl modification of adenosine (ms(2)i(6)A) is an evolutionally conserved modification found in mitochondrial (mt)-tRNAs. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) specifically converts N6-isopentenyladenosine (i(6)A) to ms(2)i(6)A at position A37 of four mt-DNA-encoded tRNAs, and the modification regulates efficient mitochondrial translation and energy metabolism in mammals. Here, we report that the ms 2 conversion mediated by CDK5RAP1 in mt-tRNAs is required to sustain glioma-initiating cell (GIC)-related traits. CDK5RAP1 maintained the self-renewal capacity, undifferentiated state, and tumorigenic potential of GICs. This regulation was not related to the translational control of mt-proteins. CDK5RAP1 abrogated the antitumor effect of i(6)A by converting i(6)A to ms (2)i(6) A and protected GICs from excessive autophagy triggered by i(6)A. The elevated activity of CDK5RAP1 contributed to the amelioration of the tumor-suppressive effect of i(6)A and promoted GIC maintenance. This work demonstrates that CDK5RAP1 is crucial for the detoxification of endogenous i(6)A and that GICs readily utilize this mechanism for survival. en-copyright= kn-copyright= en-aut-name=YamamotoTakahiro en-aut-sei=Yamamoto en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WeiFan-Yan en-aut-sei=Wei en-aut-mei=Fan-Yan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinojimaNaoki en-aut-sei=Shinojima en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurodaJun-Ichiro en-aut-sei=Kuroda en-aut-mei=Jun-Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MukasaAkitake en-aut-sei=Mukasa en-aut-mei=Akitake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TomizawaKazuhito en-aut-sei=Tomizawa en-aut-mei=Kazuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=2 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=3 en-affil=Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=4 en-affil=Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=5 en-affil=Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=6 en-affil=Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University kn-affil= affil-num=7 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=65 end-page=72 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Metabolic Profiling of the Cerebrospinal Fluid in Pediatric Epilepsy en-subtitle= kn-subtitle= en-abstract= kn-abstract= To characterize metabolic profiles within the central nervous system in epilepsy, we performed gas chromatography-tandem mass spectrometry (GC-MS/MS)-based metabolome analysis of the cerebrospinal fluid (CSF) in pediatric patients with and without epilepsy. The CSF samples obtained from 64 patients were analyzed by GC-MS/MS. Multivariate analyses were performed for two age groups, 0-5 years of age and 6-17 years of age, to elucidate the effects of epilepsy and antiepileptic drugs on the metabolites. In patients aged 0-5 years (22 patients with epilepsy, 13 without epilepsy), epilepsy patients had reduced 2-ketoglutaric acid and elevated pyridoxamine and tyrosine. In patients aged 6-17 years (12 with epilepsy, 17 without epilepsy), epilepsy patients had reduced 1,5-anhydroglucitol. Valproic acid was associated with elevated 2-aminobutyric acid, 2-ketoisocaproic acid, 4-hydroxyproline, acetylglycine, methionine, N-acetylserine, and serine. Reduced energy metabolism and alteration of vitamin B6 metabolism may play a role in epilepsy in young children. The roles of 1,5-anhydroglucitol in epilepsy in older children and in levetiracetam and zonisamide treatment remain to be explained. Valproic acid influenced the levels of amino acids and related metabolites involved in the metabolism of serine, methionine, and leucine. en-copyright= kn-copyright= en-aut-name=AkiyamaTomoyuki en-aut-sei=Akiyama en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SaigusaDaisuke en-aut-sei=Saigusa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HyodoYuki en-aut-sei=Hyodo en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UmedaKeiko en-aut-sei=Umeda en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaijoReina en-aut-sei=Saijo en-aut-mei=Reina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoshibaSeizo en-aut-sei=Koshiba en-aut-mei=Seizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiKatsuhiro en-aut-sei=Kobayashi en-aut-mei=Katsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=3 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=5 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=6 en-affil=Tohoku Medical Megabank Organization, Tohoku University kn-affil= affil-num=7 en-affil=Department of Child Neurology, Okayama University Hospital kn-affil= en-keyword=antiepileptic drugs kn-keyword=antiepileptic drugs en-keyword=gas chromatography-tandem mass spectrometry kn-keyword=gas chromatography-tandem mass spectrometry en-keyword=metabolome analysis kn-keyword=metabolome analysis en-keyword=metabolomics kn-keyword=metabolomics END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=1 end-page=6 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Promising New Anti-Cancer Strategy: Iron Chelators Targeting CSCs en-subtitle= kn-subtitle= en-abstract= kn-abstract= Iron is a trace but vital element in the human body and is necessary for a multitude of crucial processes in life. However, iron overload is known to induce carcinogenesis via oxidative stress. Cancer cells require large amounts of iron for their rapid division and cell growth. Iron was recently found to play a role in cancer stem cells (CSCs); it maintains stemness during development. Iron also plays an important role in stemness by moderating reactive oxygen species. Thus, iron metabolism in CSCs is a promising therapeutic target. In this review, we summarize the roles of iron in cancer cells and CSCs. We also summarize anti-cancer therapeutic studies with iron chelators and describe our expectation of a new therapeutic strategy for CSCs on the basis of our findings. en-copyright= kn-copyright= en-aut-name=ChenYuehua en-aut-sei=Chen en-aut-mei=Yuehua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=XingBoyi en-aut-sei=Xing en-aut-mei=Boyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=QiJiping en-aut-sei=Qi en-aut-mei=Jiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NomaKazuhiro en-aut-sei=Noma en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, the First Affiliated Hospital of Harbin Medical University kn-affil= affil-num=5 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=cancer stem cell kn-keyword=cancer stem cell en-keyword=stemness kn-keyword=stemness en-keyword=iron kn-keyword=iron en-keyword=chelation kn-keyword=chelation en-keyword=chemotherapy kn-keyword=chemotherapy END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue= article-no= start-page=154 end-page=164 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20171016 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Attenuation of CD4+ CD25+ Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug en-subtitle= kn-subtitle= en-abstract= kn-abstract= CD4+CD25+ regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of na?ve CD4+ T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1. Rapamycin and compound C, an inhibitor of AMP-activated protein kinase (AMPK) restored the iTreg generation, further indicating the involvement of mTORC1 and AMPK. The metabolic profile of iTreg, increased Glut1-expression, and reduced mitochondrial membrane-potential and ROS production of Ti-Treg aided in identifying enhanced glycolysis upon Met-treatment. The negative impact of Met on Ti-Treg may help generation of the sustained antitumor immunity. en-copyright= kn-copyright= en-aut-name=KunisadaYuki en-aut-sei=Kunisada en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EikawaShingo en-aut-sei=Eikawa en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DomaeShohei en-aut-sei=Domae en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UeharaTakenori en-aut-sei=Uehara en-aut-mei=Takenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriShohei en-aut-sei=Hori en-aut-mei=Shohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FurusawaYukihiro en-aut-sei=Furusawa en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HaseKoji en-aut-sei=Hase en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SasakiAkira en-aut-sei=Sasaki en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UdonoHeiichiro en-aut-sei=Udono en-aut-mei=Heiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Laboratory of Immunology and Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo kn-affil= affil-num=7 en-affil=Division of Biochemistry, Keio University Graduate School of Pharmaceutical Science kn-affil= affil-num=8 en-affil=Division of Biochemistry, Keio University Graduate School of Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Glycolysis kn-keyword=Glycolysis en-keyword=Regulatory T cell (Treg) kn-keyword=Regulatory T cell (Treg) en-keyword=Tumor immunity kn-keyword=Tumor immunity en-keyword=Tumor microenvironment kn-keyword=Tumor microenvironment en-keyword=mTOR kn-keyword=mTOR END start-ver=1.4 cd-journal=joma no-vol=400 cd-vols= no-issue= article-no= start-page=145 end-page=147 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190515 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A unique Japanese CPEO family with a novel homozygous m.14819?T?>?G (p. S25A) substitution en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TadokoroKoh en-aut-sei=Tadokoro en-aut-mei=Koh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SatoKota en-aut-sei=Sato en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SasakiRyo en-aut-sei=Sasaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiYoshiaki en-aut-sei=Takahashi en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GotoYu-ichi en-aut-sei=Goto en-aut-mei=Yu-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Medical Genome Center (MGC), Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience (NIN), National Center of Neurology and Psychiatry kn-affil= affil-num=11 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=CPEO kn-keyword=CPEO en-keyword=Homozygous kn-keyword=Homozygous en-keyword=Mitochondrial DNA kn-keyword=Mitochondrial DNA END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=1 article-no= start-page=856 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Integrated transcriptomic and proteomic analyses of a molecular mechanism of radular teeth biomineralization in Cryptochiton stelleri en-subtitle= kn-subtitle= en-abstract= kn-abstract= Many species of chiton are known to deposit magnetite (Fe3O4) within the cusps of their heavily mineralized and ultrahard radular teeth. Recently, much attention has been paid to the ultrastructural design and superior mechanical properties of these radular teeth, providing a promising model for the development of novel abrasion resistant materials. Here, we constructed de novo assembled transcripts from the radular tissue of C. stelleri that were used for transcriptome and proteome analysis. Transcriptomic analysis revealed that the top 20 most highly expressed transcripts in the non-mineralized teeth region include the transcripts encoding ferritin, while those in the mineralized teeth region contain a high proportion of mitochondrial respiratory chain proteins. Proteomic analysis identified 22 proteins that were specifically expressed in the mineralized cusp. These specific proteins include a novel protein that we term radular teeth matrix protein1 (RTMP1), globins, peroxidasins, antioxidant enzymes and a ferroxidase protein. This study reports the first de novo transcriptome assembly from C. stelleri, providing a broad overview of radular teeth mineralization. This new transcriptomic resource and the proteomic profiles of mineralized cusp are valuable for further investigation of the molecular mechanisms of radular teeth mineralization in chitons. en-copyright= kn-copyright= en-aut-name=NemotoMichiko en-aut-sei=Nemoto en-aut-mei=Michiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=RenDongni en-aut-sei=Ren en-aut-mei=Dongni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HerreraSteven en-aut-sei=Herrera en-aut-mei=Steven kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PanSongqin en-aut-sei=Pan en-aut-mei=Songqin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TamuraTakashi en-aut-sei=Tamura en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=InagakiKenji en-aut-sei=Inagaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Kisailus David en-aut-sei=Kisailus en-aut-mei=David kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Graduate School of Environmental and life Science, Okayama University kn-affil= affil-num=2 en-affil= Materials Science and Engineering Program, University of California kn-affil= affil-num=3 en-affil= Materials Science and Engineering Program, University of California kn-affil= affil-num=4 en-affil= W. M. Keck Proteomics Laboratory, Institute for Integrative Genome Biology, University of California kn-affil= affil-num=5 en-affil= Graduate School of Environmental and life Science, Okayama University kn-affil= affil-num=6 en-affil= Graduate School of Environmental and life Science, Okayama University kn-affil= affil-num=7 en-affil=Materials Science and Engineering Program, University of California kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=11 article-no= start-page=e50082 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20121126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial localization of ABC transporter ABCG2 and its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol. en-copyright= kn-copyright= en-aut-name=KobuchiHirotsugu en-aut-sei=Kobuchi en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriyaKoko en-aut-sei=Moriya en-aut-mei=Koko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OginoTetsuya en-aut-sei=Ogino en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaHirofumi en-aut-sei=Fujita en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueKeiji en-aut-sei=Inoue en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShuinTaro en-aut-sei=Shuin en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaTatsuji en-aut-sei=Yasuda en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UtsumiToshihiko en-aut-sei=Utsumi en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=1 Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University kn-affil= affil-num=3 en-affil=Department of Nursing Science, Faculty of Health and Welfare Science, Okayama Prefectural University kn-affil= affil-num=4 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Urology, Kochi Medical School kn-affil= affil-num=6 en-affil=Department of Urology, Kochi Medical School kn-affil= affil-num=7 en-affil=1 Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue= article-no= start-page=12 end-page=17 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Species identification of a laboratory strain belonging to the family Arvicolinae kn-title=種名が不明なミズハタネズミ亜科系統の種の同定 en-subtitle= kn-subtitle= en-abstract= kn-abstract= This study investigated the taxonomic status of a laboratory strain belonging to the family Arvicolinae for which the wild species name is unknown. This vole strain, though considered formerly a Lemming, was distinguishable from any Lemmus species by features of its appearance, skull and molar morphology, and conventional chromosomal pattern. Subsequently, we read the nucleotide sequence of the mitochondrial cytochrome b (Cyb) gene and constructed a molecular phylogenetic tree. We found that this vole strain belongs to the same clade as Microtus guenthe en-copyright= kn-copyright= en-aut-name=TakahataSatoshi en-aut-sei=Takahata en-aut-mei=Satoshi kn-aut-name=高畑智 kn-aut-sei=高畑 kn-aut-mei=智 aut-affil-num=1 ORCID= en-aut-name=IsemuraNatsumi en-aut-sei=Isemura en-aut-mei=Natsumi kn-aut-name=伊勢村夏実 kn-aut-sei=伊勢村 kn-aut-mei=夏実 aut-affil-num=2 ORCID= en-aut-name=MekadaKazuyuki en-aut-sei=Mekada en-aut-mei=Kazuyuki kn-aut-name=目加田和之 kn-aut-sei=目加田 kn-aut-mei=和之 aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Zoology, Faculty of Science, Okayama University of Science kn-affil=岡山理科大学 理学部 動物学科 affil-num=2 en-affil=Department of Zoology, Faculty of Science, Okayama University of Science kn-affil=岡山理科大学 理学部 動物学科 affil-num=3 en-affil=Department of Zoology, Faculty of Science, Okayama University of Science kn-affil=岡山理科大学 理学部 動物学科 END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=11 article-no= start-page=e50082 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20121126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial localization of ABC transporter ABCG2 and its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation en-subtitle= kn-subtitle= en-abstract= kn-abstract= Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol. en-copyright= kn-copyright= en-aut-name=KobuchiHirotsugu en-aut-sei=Kobuchi en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriyaKoko en-aut-sei=Moriya en-aut-mei=Koko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OginoTetsuya en-aut-sei=Ogino en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaHirofumi en-aut-sei=Fujita en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueKeiji en-aut-sei=Inoue en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShuinTaro en-aut-sei=Shuin en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaTatsuji en-aut-sei=Yasuda en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UtsumiToshihiko en-aut-sei=Utsumi en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue= article-no= start-page=39 end-page=42 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20170201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Mitochondrial dynamics in mammalian oocytes kn-title=哺乳類卵子におけるミトコンドリアの動態 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Subcellular distribution of mitochondria are reorganized during development of the oocyte into a fertilizable egg. In growing oocytes, mitochondria are heterogeneously distributed in the cytoplasm, whereas they diffuse throughout the cytoplasm in fully-grown oocytes. GFP-labeled mitochondria demonstrate that oocyte maturation involves dynamic redistribution of the mitochondria, whose process is associated with microtubule organization. These spatio-temporal regulations of mitochondria in oocytes may be an important process in the preparation for fertilization and subsequent embryonic development. en-copyright= kn-copyright= en-aut-name=WakaiTakuya en-aut-sei=Wakai en-aut-mei=Takuya kn-aut-name=若井拓哉 kn-aut-sei=若井 kn-aut-mei=拓哉 aut-affil-num=1 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil=岡山大学大学院環境生命科学研究科 en-keyword=Oocyte kn-keyword=Oocyte en-keyword=Mitochondria kn-keyword=Mitochondria en-keyword=Meiosis kn-keyword=Meiosis en-keyword=Cytoskeleton kn-keyword=Cytoskeleton en-keyword=Endoplasmic reticulum kn-keyword=Endoplasmic reticulum END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=3 article-no= start-page=151 end-page=158 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mitochondria are involved in active and dynamic processes, such as mitochondrial biogenesis, fission, fusion and mitophagy to maintain mitochondrial and cellular functions. In obesity and type 2 diabetes, impaired oxidation, reduced mitochondrial contents, lowered rates of oxidative phosphorylation and excessive reactive oxygen species (ROS) production have been reported. Mitochondrial biogenesis is regulated by various transcription factors such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptors (PPARs), estrogen-related receptors (ERRs), and nuclear respiratory factors (NRFs). Mitochondrial fusion is promoted by mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy 1 (OPA1), while fission is governed by the recruitment of dynamin-related protein 1 (DRP1) by adaptor proteins such as mitochondrial fission factor (MFF), mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51), and fission 1 (FIS1). Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARKIN promote DRP1-dependent mitochondrial fission, and the outer mitochondrial adaptor MiD51 is required in DRP1 recruitment and PARKIN-dependent mitophagy. This review describes the molecular mechanism of mitochondrial dynamics, its abnormality in diabetes and obesity, and pharmaceuticals targeting mitochondrial biogenesis, fission, fusion and mitophagy. en-copyright= kn-copyright= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakatsukaAtsuko en-aut-sei=Nakatsuka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=fusion kn-keyword=fusion en-keyword=fission kn-keyword=fission en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=mitochondria kn-keyword=mitochondria en-keyword=diabetes kn-keyword=diabetes END start-ver=1.4 cd-journal=joma no-vol=127 cd-vols= no-issue=2 article-no= start-page=103 end-page=109 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20150803 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Role of COLXV/XVV gene, Multiplexin, as a basement membrane toolkit kn-title=基底膜ツールキットとしてのXV/XVV型コラーゲン遺伝子の機能 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=OohashiToshitaka en-aut-sei=Oohashi en-aut-mei=Toshitaka kn-aut-name=大橋俊孝 kn-aut-sei=大橋 kn-aut-mei=俊孝 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 en-keyword=基底膜 kn-keyword=基底膜 en-keyword=ツールキット kn-keyword=ツールキット en-keyword=XV/XVV型コラーゲン kn-keyword=XV/XVV型コラーゲン en-keyword=プロテオグリカン kn-keyword=プロテオグリカン en-keyword=ミトコンドリア kn-keyword=ミトコンドリア END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=7 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140701 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=L-Carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract=Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC). Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid), an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1) high-fat diet (HFD) (control group); 2) HFD mixed with 0.28% L-carnitine (L-carnitine group); and 3) HFD mixed with 0.01% alpha-tocopherol (alpha-tocopherol group). After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial beta-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although alpha-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by upregulating the mitochondrial beta-oxidation and redox system. en-copyright= kn-copyright= en-aut-name=IshikawaHisashi en-aut-sei=Ishikawa en-aut-mei=Hisashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsuzakiRyuichiro en-aut-sei=Tsuzaki en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasunakaTetsuya en-aut-sei=Yasunaka en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoikeKazuko en-aut-sei=Koike en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimomuraYasuyuki en-aut-sei=Shimomura en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SekiHiroyuki en-aut-sei=Seki en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsushitaHiroshi en-aut-sei=Matsushita en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MiyakeYasuhiro en-aut-sei=Miyake en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IkedaFusao en-aut-sei=Ikeda en-aut-mei=Fusao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=9 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=10 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=11 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=12 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=13 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20141231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=L-カルニチンはミトコンドリア経路の発現を高め、マウスにおける非アルコール性脂肪性肝炎の病態進行を抑制する kn-title=L-Carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=IshikawaHisashi en-aut-sei=Ishikawa en-aut-mei=Hisashi kn-aut-name=石川久 kn-aut-sei=石川 kn-aut-mei=久 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=26 cd-vols= no-issue=3 article-no= start-page=285 end-page=298 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuroprotective Effects of Metallothionein Against Rotenone-Induced Myenteric Neurodegeneration in Parkinsonian Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as well as non-motor symptoms that precede the onset of motor symptoms. Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD pathology in the central nervous system (CNS) and enteric nervous system (ENS). We reported previously that metallothioneins (MTs) released from astrocytes can protect dopaminergic neurons against oxidative stress. The present study examined the changes in MT expression by chronic systemic rotenone administration in the striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6 weeks caused neurodegeneration, increased MT expression with astrocytes activation in the striatum and myenteric plexus. MT KO mice showed more severe myenteric neuronal damage by rotenone administration after 4 weeks than wild-type mice, accompanied by reduced astroglial activation. In primary cultured mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in dopaminergic neurons, which was complemented by addition of recombinant protein. The present results suggest that MT seems to provide protection against neurodegeneration in ENS of rotenone-induced PD model mice. en-copyright= kn-copyright= en-aut-name=MurakamiShinki en-aut-sei=Murakami en-aut-mei=Shinki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SogawaNorio en-aut-sei=Sogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyoshiKo en-aut-sei=Miyoshi en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Brain Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Brain Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Dent Pharmacol affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Brain Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Brain Sci en-keyword=Parkinson's disease kn-keyword=Parkinson's disease en-keyword=Rotenone kn-keyword=Rotenone en-keyword=Enteric nervous system kn-keyword=Enteric nervous system en-keyword=Astrocytes kn-keyword=Astrocytes en-keyword=Metallothionein kn-keyword=Metallothionein END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=3 article-no= start-page=203 end-page=208 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20141201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Modulation of neuronal function and neuroprotection by astrocytes kn-title=アストロサイトによる神経機能修飾とパーキンソン病での神経保護 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name=浅沼幹人 kn-aut-sei=浅沼 kn-aut-mei=幹人 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 神経ゲノム学 en-keyword=アストロサイト kn-keyword=アストロサイト en-keyword=抗酸化防御機構 kn-keyword=抗酸化防御機構 en-keyword=パーキンソン病 kn-keyword=パーキンソン病 en-keyword=メタロチオネイン kn-keyword=メタロチオネイン en-keyword=Nrf2 kn-keyword=Nrf2 END start-ver=1.4 cd-journal=joma no-vol=150 cd-vols= no-issue=1 article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201302 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acetyl-L-carnitine suppresses thyroid hormone-induced and spontaneous anuran tadpole tail shortening en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mitochondrial membrane permeability transition (MPT) plays a crucial role in apoptotic tail shortening during anuran metamor phosis. L-carnitine is known to shuttle free fatty acids (FFAs) from the cytosol into mitochondria matrix for -oxidation and energy production, and in a previous study we found that treatment with L-carnitine suppresses 3, 3', 5-triiodothyronine (T3) and FFA-induced MPT by reducing the level of FFAs. In the present study we focus on acetyl-L-carnitine, which is also involved in fatty acid oxidation, to determine its effect on T3-induced tail regression in Rana rugosa tadpoles and spontaneous tail regression in Xenopus laevis tadpoles. The ladder-like DNA profile and increases in caspase-3 and caspase-9 indicative of apoptosis in the tails of T3-treated tadpoles were found to be suppressed by the addition of acetyl-L-carnitine. Likewise, acetyl-L-carnitine was found to inhibit thyroid hormone regulated spontaneous metamorphosis in X. laevis tadpoles, accompanied by decreases in caspase and phospholipase A2 activity, as well as non-ladder-like DNA profiles. These findings support our previous conclusion that elevated levels of FFAs initiate MPT and activate the signaling pathway controlling apoptotic cell death in tadpole tails during anuran metamorphosis. en-copyright= kn-copyright= en-aut-name=HanadaHideki en-aut-sei=Hanada en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobuchiHirotsugu en-aut-sei=Kobuchi en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoMasanao en-aut-sei=Yamamoto en-aut-mei=Masanao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KashiwagiKeiko en-aut-sei=Kashiwagi en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatsuKenjiro en-aut-sei=Katsu en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UtsumiToshihiko en-aut-sei=Utsumi en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KashiwagiAkihiko en-aut-sei=Kashiwagi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SasakiJunzo en-aut-sei=Sasaki en-aut-mei=Junzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=InoueMasayasu en-aut-sei=Inoue en-aut-mei=Masayasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Hiroshima Univ, Inst Amphibian Biol, Grad Sch Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Cell Chem, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Cytol & Histol, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Hiroshima Univ, Inst Amphibian Biol, Grad Sch Sci affil-num=5 en-affil= kn-affil=Kumamoto Univ, Div Pattern Format, Dept Organogenesis, Inst Mol Embryol & Genet affil-num=6 en-affil= kn-affil=Yamaguchi Univ, Grad Sch Med affil-num=7 en-affil= kn-affil=Hiroshima Univ, Inst Amphibian Biol, Grad Sch Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Cytol & Histol, Grad Sch Med Dent & Pharmaceut Sci affil-num=9 en-affil= kn-affil=Osaka City Univ, Sch Med, Dept Biochem & Mol Pathol affil-num=10 en-affil= kn-affil=Okayama Univ, Dept Cytol & Histol, Grad Sch Med Dent & Pharmaceut Sci END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=2 article-no= start-page=83 end-page=86 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The 2013 Incentive Award of the Okayama Medical Association in General Medical Science (2013 Yuuki Prize) kn-title=平成25年度岡山医学会賞 総合研究奨励賞(結城賞) en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MurataHitoshi en-aut-sei=Murata en-aut-mei=Hitoshi kn-aut-name=村田等 kn-aut-sei=村田 kn-aut-mei=等 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 細胞生物学 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=筋萎縮性側索硬化症マウスモデルにおけるミトコンドリア融合と分裂タンパク質の動的変化 kn-title=Mitochondrial Fusion and Fission Proteins Expression Dynamically Change in a Murine Model of Amyotrophic Lateral Sclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=?文涛 kn-aut-sei=? kn-aut-mei=文涛 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=1 article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Oral Administration of Non-genotoxic Hepato-hypertrophic Compounds on Metabolic Potency of Rat Liver en-subtitle= kn-subtitle= en-abstract= kn-abstract=It remains uncertain why non-genotoxic compounds that result in liver hypertrophy cause liver tumors. In an effort to resolve this issue, we examined whether liver post-mitochondrial fraction (S9) prepared from rats treated with non-genotoxic compounds affected the genotoxicity of pro-mutagens. Known hepatotoxic compounds, such as piperonyl butoxide (PBO), decabromodiphenyl ether (DBDE), beta-naphthoflavone (BNF), indole-3-carbinol (I3C) and acetaminophen (AA), were orally administered to male and female F344 rats at doses sufficient to cause liver hypertrophy. Rats received diets containing each test compound for 3 days, 4 weeks or 13 weeks, and were then kept for 4 weeks without the test chemical. S9 prepared from the livers of each group was used for the Ames test with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), benzo[a]pyrene (BaP) and N-nitrosodimethylamine (NDMA). In both sexes, liver hypertrophy was observed following administration of all test compounds, and was then reversed to the control state when administration ceased. The mutagenicity of MeIQx, BaP and NDMA increased with the use of S9 derived from rats treated with non-genotoxic compounds other than AA. DBDE administration had a marked effect on the mutagenicity of BaP (over a 30-fold increase in females) and NDMA (about a 20-fold increase in males). To estimate the involvement of metabolic enzymes in the alteration of mutagenicity, we measured the activity of ethoxyresorufin-O-deethylase (EROD) and methoxyresorufin-O-demethylase (MROD) (phase I enzymes), and UDP-glucuronosyltransferase (UGT) and glutathione S-transferase (GST) (phase II enzymes) in each S9 sample. The activity of phase I enzymes increased, even at the 3rd day following administration, and then decreased gradually, except in the case of AA, while the activity of phase II enzymes increased slightly. These results suggest that non-genotoxic hepato-hypertrophic compounds may be partly involved in carcinogenesis by modulating the metabolism of pre-carcinogens incorporated from the environment, in a manner that is dependent on sex and pre-incorporated chemicals. en-copyright= kn-copyright= en-aut-name=FangXing en-aut-sei=Fang en-aut-mei=Xing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NunoshibaTatsuo en-aut-sei=Nunoshiba en-aut-mei=Tatsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshidaMidori en-aut-sei=Yoshida en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishikawaAkiyoshi en-aut-sei=Nishikawa en-aut-mei=Akiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NemotoKiyomitsu en-aut-sei=Nemoto en-aut-mei=Kiyomitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DegawaMasakuni en-aut-sei=Degawa en-aut-mei=Masakuni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ArimotoSakae en-aut-sei=Arimoto en-aut-mei=Sakae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoKeinosuke en-aut-sei=Okamoto en-aut-mei=Keinosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakahashiEizo en-aut-sei=Takahashi en-aut-mei=Eizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NegishiTomoe en-aut-sei=Negishi en-aut-mei=Tomoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=2 en-affil= kn-affil=International Christian University affil-num=3 en-affil= kn-affil=National Institute of Health Sciences affil-num=4 en-affil= kn-affil=National Institute of Health Sciences affil-num=5 en-affil= kn-affil=School of Pharmaceutical Sciences, University of Shizuoka affil-num=6 en-affil= kn-affil=School of Pharmaceutical Sciences, University of Shizuoka affil-num=7 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=8 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=9 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=10 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University en-keyword=liver hypertrophic compound kn-keyword=liver hypertrophic compound en-keyword=metabolism kn-keyword=metabolism en-keyword=mutation kn-keyword=mutation en-keyword=Ames test kn-keyword=Ames test END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=5 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130507 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of Biliverdin Administration on Acute Lung Injury Induced by Hemorrhagic Shock and Resuscitation in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. Biliverdin or vehicle was administered to the rats 1 h before sham or hemorrhagic shock-inducing surgery. The sham-operated rats underwent all surgical procedures except bleeding. To induce hemorrhagic shock, rats were bled to achieve a mean arterial pressure of 30 mmHg that was maintained for 60 min, followed by resuscitation with shed blood. Histopathological changes in the lungs were evaluated by histopathological scoring analysis. Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs. Hemorrhagic shock and resuscitation resulted in prominent histopathological damage, including congestion, edema, cellular infiltration, and hemorrhage. Biliverdin administration prior to hemorrhagic shock and resuscitation significantly ameliorated these lung injuries as judged by histopathological improvement. After hemorrhagic shock and resuscitation, inflammatory gene expression of tumor necrosis factor-alpha and inducible nitric oxide synthase were increased by 18- and 8-fold, respectively. Inflammatory gene expression significantly decreased when biliverdin was administered prior to hemorrhagic shock and resuscitation. Moreover, after hemorrhagic shock and resuscitation, lung 8-hydroxy-2' deoxyguanosine levels in mitochondrial DNA expressed in the pulmonary interstitium increased by 1.5-fold. Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the control animals. We also confirmed that biliverdin administration after hemorrhagic shock and resuscitation had protective effects on lung injury. Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms. en-copyright= kn-copyright= en-aut-name=KosakaJunko en-aut-sei=Kosaka en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorimatsuHiroshi en-aut-sei=Morimatsu en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiToru en-aut-sei=Takahashi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShimizuHiroko en-aut-sei=Shimizu en-aut-mei=Hiroko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanishiSusumu en-aut-sei=Kawanishi en-aut-mei=Susumu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoriEmiko en-aut-sei=Omori en-aut-mei=Emiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EndoYasumasa en-aut-sei=Endo en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TamakiNaofumi en-aut-sei=Tamaki en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaManabu en-aut-sei=Morita en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MoritaKiyoshi en-aut-sei=Morita en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Prevent Dent affil-num=8 en-affil= kn-affil=Univ Tokushima, Grad Sch, Dept Prevent Dent, Inst Hlth Biosci affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Prevent Dent affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=9 article-no= start-page=1000 end-page=1006 dt-received= dt-revised= dt-accepted= dt-pub-year=2009 dt-pub=200909 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mortality rate of patients with asymptomatic primary biliary cirrhosis diagnosed at age 55 years or older is similar to that of the general population en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent routine testing for liver function and anti-mitochondrial antibodies has increased the number of newly diagnosed patients with primary biliary cirrhosis (PBC). This study investigated the prognosis of asymptomatic PBC patients, focusing on age difference, to clarify its effect on the prognosis of PBC patients. The study was a systematic cohort analysis of 308 consecutive patients diagnosed with asymptomatic PBC. We compared prognosis between the elderly (55 years or older at the time of diagnosis) and the young patients (< 55 years). The mortality rate of the patients was also compared with that of an age- and gender-matched general population. The elderly patients showed a higher aspartate aminotransferase-to-platelet ratio, and lower alanine aminotransferase level than the young patients (P < 0.01 and P = 0.03, respectively). The two groups showed similar values for alkaline phosphatase and immunoglobulin M. Death in the young patients was more likely to be due to liver failure (71%), while the elderly were likely to die from other causes before the occurrence of liver failure (88%; P < 0.01), especially from malignancies (35%). The mortality rate of the elderly patients was not different from that of the age- and gender-matched general population (standardized mortality ratio, 1.1; 95% confidence interval, 0.6-1.7), although this rate was significantly higher than that of the young patients (P = 0.044). PBC often presents as more advanced disease in elderly patients than in the young. However, the mortality rate of the elderly patients is not different from that of an age- and gender-matched general population. en-copyright= kn-copyright= en-aut-name=KubotaJunichi en-aut-sei=Kubota en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaFusao en-aut-sei=Ikeda en-aut-mei=Fusao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TeradaRyo en-aut-sei=Terada en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobashiHaruhiko en-aut-sei=Kobashi en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiokaShin-ichi en-aut-sei=Fujioka en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoRyoichi en-aut-sei=Okamoto en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BabaShinsuke en-aut-sei=Baba en-aut-mei=Shinsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorimotoYouichi en-aut-sei=Morimoto en-aut-mei=Youichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AndoMasaharu en-aut-sei=Ando en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MakinoYasuhiro en-aut-sei=Makino en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TaniguchiHideaki en-aut-sei=Taniguchi en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YasunakaTetsuya en-aut-sei=Yasunaka en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MiyakeYasuhiro en-aut-sei=Miyake en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol affil-num=5 en-affil= kn-affil=Okayama Saiseikai Gen Hosp, Dept Internal Med affil-num=6 en-affil= kn-affil=Hiroshima City Hosp, Dept Internal Med affil-num=7 en-affil= kn-affil=Kagawa Prefectural Cent Hosp, Dept Internal Med affil-num=8 en-affil= kn-affil=Fukuyama City Hosp, Dept Internal Med affil-num=9 en-affil= kn-affil=Mitoyo Gen Hosp, Dept Internal Med affil-num=10 en-affil= kn-affil=Natl Hosp Org Iwakuni Clin Ctr, Dept Gastroenterol affil-num=11 en-affil= kn-affil=Sumitomo Besshi Hosp, Dept Internal Med affil-num=12 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol affil-num=13 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol affil-num=14 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol affil-num=15 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol en-keyword=Primary biliary cirrhosis kn-keyword=Primary biliary cirrhosis en-keyword=Age difference kn-keyword=Age difference en-keyword=Mortality rate kn-keyword=Mortality rate END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue=3 article-no= start-page=201 end-page=204 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20131202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Hydrogen as a treatment candidate for non-alcoholic steatohepatitis kn-title=NASHに対する水素分子の有用性 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=KawaiDaisuke en-aut-sei=Kawai en-aut-mei=Daisuke kn-aut-name=河合大介 kn-aut-sei=河合 kn-aut-mei=大介 aut-affil-num=1 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name=高木章乃夫 kn-aut-sei=高木 kn-aut-mei=章乃夫 aut-affil-num=2 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name=山本和秀 kn-aut-sei=山本 kn-aut-mei=和秀 aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 消化器・肝臓内科学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 消化器・肝臓内科学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 消化器・肝臓内科学 en-keyword=酸化ストレス kn-keyword=酸化ストレス en-keyword=水素水 kn-keyword=水素水 en-keyword=NASH kn-keyword=NASH en-keyword=肝腫瘍 kn-keyword=肝腫瘍 END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=11 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20121126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial Localization of ABC Transporter ABCG2 and Its Function in 5-Aminolevulinic Acid-Mediated Protoporphyrin IX Accumulation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol. en-copyright= kn-copyright= en-aut-name=KobuchiHirotsugu en-aut-sei=Kobuchi en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriyaKoko en-aut-sei=Moriya en-aut-mei=Koko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OginoTetsuya en-aut-sei=Ogino en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FujitaHirofumi en-aut-sei=Fujita en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoueKeiji en-aut-sei=Inoue en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShuinTaro en-aut-sei=Shuin en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaTatsuji en-aut-sei=Yasuda en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UtsumiToshihiko en-aut-sei=Utsumi en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Cell Chem, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Yamaguchi Univ, Grad Sch Med affil-num=3 en-affil= kn-affil=Okayama Prefectural Univ, Dept Nursing Sci, Fac Hlth & Welf Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Cytol & Histol, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Kochi Med Sch, Dept Urol affil-num=6 en-affil= kn-affil=Kochi Med Sch, Dept Urol affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Cell Chem, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Cytol & Histol, Grad Sch Med Dent & Pharmaceut Sci affil-num=9 en-affil= kn-affil=Yamaguchi Univ, Grad Sch Med END start-ver=1.4 cd-journal=joma no-vol=66 cd-vols= no-issue=4 article-no= start-page=317 end-page=327 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Water Extract of Vitis coignetiae Pulliat Leaves Attenuates Oxidative Stress and Inflammation in Progressive NASH Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study aimed to investigate the therapeutic effects of the water extract of leaves of Vitis coignetiae Pulliat (VCPL) on nonalcoholic steatohepatitis (NASH) with advanced fibrosis, as our previous study exhibited its preventive effect on NASH. The NASH animal model [PCT/JP2007/52477] was prepared by loading recurrent and intermittent hypoxemia stress to a rat with fatty liver, which resembled the condition occurring in patients with obstructive sleep apnea (OSA) and fatty liver, who have a high incidence of NASH. Intermittent hypoxemia stress is regarded as a condition similar to warm ischemia followed by re-oxygenation, which induces oxidative stress (OS). The daily 100 or 300mg/kg VCPL administrations were performed for 3 weeks perorally beginning at the time of detection of advanced liver fibrosis. The therapeutic efficacy of VCPL on NASH was demonstrated by the reduction of the leakage of hepato-biliary enzymes and the amelioration of liver fibrosis. The OS elevation in NASH rats was measured based on the derivation of reactive oxygen species from liver mitochondrial energy metabolism and on the decrease in plasma SOD-like activity. The aggravation of inflammatory responses was demonstrated by the neutrophil infiltration (elevated myeloperoxidase activity) and the progression of fibrosis in the livers of NASH rats. In addition, the NASH rats without VCPL treatment also exhibited activation of nuclear factor-κB, a key factor in the link between oxidative stress and inflammation. All of these changes were reduced dose-dependently by the VCPL administration. These findings indicate that VCPL may improve hepatic fibrosis or at least suppress the progression of NASH, by breaking the crosstalk between OS and inflammation. en-copyright= kn-copyright= en-aut-name=PakWing en-aut-sei=Pak en-aut-mei=Wing kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakayamaFusako en-aut-sei=Takayama en-aut-mei=Fusako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasegawaAzusa en-aut-sei=Hasegawa en-aut-mei=Azusa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MankuraMitsumasa en-aut-sei=Mankura en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EgashiraToru en-aut-sei=Egashira en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UekiKeiji en-aut-sei=Ueki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamotoKazuo en-aut-sei=Nakamoto en-aut-mei=Kazuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KawasakiHiromu en-aut-sei=Kawasaki en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoriAkitane en-aut-sei=Mori en-aut-mei=Akitane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Department of Clinical Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Clinical Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Clinical Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Anti-Aging Food Sciences, Okayama University Graduate School of Medicine affil-num=5 en-affil= kn-affil=Department of Clinical Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Hiruzen Winery Co., Ltd affil-num=7 en-affil= kn-affil=Department of Clinical Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Department of Clinical Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Department of Anti-Aging Food Sciences, Okayama University Graduate School of Medicine en-keyword=non-alcoholic steatohepatitis kn-keyword=non-alcoholic steatohepatitis en-keyword=antioxidative kn-keyword=antioxidative en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=anti-inflammation kn-keyword=anti-inflammation en-keyword=Vitis coignetiae Pulliat kn-keyword=Vitis coignetiae Pulliat END start-ver=1.4 cd-journal=joma no-vol=123 cd-vols= no-issue=3 article-no= start-page=197 end-page=206 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20111201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=A new paradigm for the treatment of lifestyle-related diseases : Microinflammation as a novel therapeutic target kn-title=生活習慣病治療のパラダイムシフト―慢性炎症を標的とした治療戦略― en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=ShikataKenichi en-aut-sei=Shikata en-aut-mei=Kenichi kn-aut-name=四方賢一 kn-aut-sei=四方 kn-aut-mei=賢一 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学病院 新医療研究開発センター en-keyword=生活習慣病 kn-keyword=生活習慣病 en-keyword=メタボリック症候群 kn-keyword=メタボリック症候群 en-keyword=糖尿病 kn-keyword=糖尿病 en-keyword=炎症 kn-keyword=炎症 en-keyword=心血管疾患 kn-keyword=心血管疾患 END start-ver=1.4 cd-journal=joma no-vol=65 cd-vols= no-issue=1 article-no= start-page=1 end-page=10 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=201102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Regulation of Mitochondrial Dynamics and Neurodegenerative Diseases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mitochondria are important cellular organelles in most metabolic processes and have a highly dynamic nature, undergoing frequent fission and fusion. The dynamic balance between fission and fusion plays critical roles in mitochondrial functions. In recent studies, several large GTPases have been identified as key molecular factors in mitochondrial fission and fusion. Moreover, the posttranslational modifications of these large GTPases, including phosphorylation, ubiquitination and SUMOylation, have been shown to be involved in the regulation of mitochondrial dynamics. Neurons are particularly sensitive and vulnerable to any abnormalities in mitochondrial dynamics, due to their large energy demand and long extended processes. Emerging evidences have thus indicated a strong linkage between mitochondria and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. In this review, we will describe the regulation of mitochondrial dynamics and its role in neurodegenerative diseases. en-copyright= kn-copyright= en-aut-name=HanXiao-Jian en-aut-sei=Han en-aut-mei=Xiao-Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TomizawaKazuhito en-aut-sei=Tomizawa en-aut-mei=Kazuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhmoriIori en-aut-sei=Ohmori en-aut-mei=Iori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishikiTei-ichi en-aut-sei=Nishiki en-aut-mei=Tei-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsushitaMasayuki en-aut-sei=Matsushita en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuiHideki en-aut-sei=Matsui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Molecular and Cellular Physiology, School of Medicine, University of the Ryukyus affil-num=7 en-affil= kn-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=mitochondria kn-keyword=mitochondria en-keyword=phosphorylation kn-keyword=phosphorylation en-keyword=ubiquitination kn-keyword=ubiquitination en-keyword=SUMOylation kn-keyword=SUMOylation en-keyword=neurodegeneration kn-keyword=neurodegeneration END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=9-2 article-no= start-page=6167 end-page=6172 dt-received= dt-revised= dt-accepted= dt-pub-year=1959 dt-pub=19590910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Intracellular Distribution of Histamine in Dog's Liver and Its Release by Intravenously Injected Drugs kn-title=犬肝臓の細胞内顆粒Histamineと生体内投与薬物によるその遊離 en-subtitle= kn-subtitle= en-abstract= kn-abstract=0.25M sucrose homogenate of dog's liver was fractionated by differential centrifugation as described by Schneider. About half of histamine of the whole homogenate was found in the mitochondrial fraction. Smears were made from each fractions, fixed in 1 per cent basic lead acetate in 50 per cent alcohol and stained with 0.1 per cent aqueous solution of toluidine blue. Microscopic observation showed that the mitochondrial fraction contains a large amount of very small round metachromatic particles, which are indistinguishable from extruded granules outside of the mast cells similarly stained in the stamp preparation from the liver slice. These observations confirm the finding of Mota and his co-workers and this fact in all probability indicates that the higher histamine concentration of the mitochondrial fraction of dog's liver might be due to contamination with mast cell granules. Intravenous administration of 3 mg/kg sinomenine or 150 to 500 mg/kg peptone into dogs resulted in a significant release of histamine from the mitochondrial fraction with some variable loss from other subcellular fraction. en-copyright= kn-copyright= en-aut-name=JinzenjiKei en-aut-sei=Jinzenji en-aut-mei=Kei kn-aut-name=秦泉寺圭 kn-aut-sei=秦泉寺 kn-aut-mei=圭 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部薬理学教室 END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=6-1 article-no= start-page=2869 end-page=2884 dt-received= dt-revised= dt-accepted= dt-pub-year=1959 dt-pub=19590501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Electronmicroscopic Studies on the Functional Differentiation of the Skeletal Muscle Fibers kn-title=骨格筋における筋線維の機能分化に関する電子顕微鏡的研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In his electronmicroscopic observations conducted on the red muscle fibers and white muscle fiders with the use of M. soleus and M. gastrocnemius in rabbits and cats, the author obtained the following results. 1. The source of functional differentiation in the red muscle fibers and white muscle fibers exists only in sarcoplasm, and no marked differences can be seen between the red and white muscle fibers as regards their myofibrils, nuclei, and sarcolemmas. 2. Mitochondria of the red muscle fibers are either round or elliptical in shape and are dense and numerous in the muscle fibers; while mitochondria of the white muscle fibers are slender and extremely less in number. 3. Mitochondrial cristae of the red muscle fibers are projecting like a cog-wheel but few in number, while those of the white muscle fibers are arranged at right angle to the long axis of the mitochondria and forming a dense crease. 4. Judging from the relationship between the shape and number of mitochondria as well as from the state of cristae, there seems to exist an intermediary type of muscle fibers between the red and white muscle fibers. 5. The sarcoplasmic reticnlum is well developed in the white muscle fibers. 6. The structural differences of sarcoplasm in these two muscle fibers coincide well with the differences in the function and energy metabolism of the two. en-copyright= kn-copyright= en-aut-name=MurayamaMasanori en-aut-sei=Murayama en-aut-mei=Masanori kn-aut-name=村山正則 kn-aut-sei=村山 kn-aut-mei=正則 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第1外科教室 END start-ver=1.4 cd-journal=joma no-vol=102 cd-vols= no-issue=11-12 article-no= start-page=1345 end-page=1350 dt-received= dt-revised= dt-accepted= dt-pub-year=1990 dt-pub=199012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effect of chlordane on rat liver mitochondrial respiration kn-title=クロルデンのラット肝ミトコンドリアの呼吸活性に対する作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In attempting to clarify the toxicity of chlordane, its effects on respiratory activities in hepatic mitochondria and on electron transport in sonicated submitochondrial particles were examined. State 3 and 4 respiration, and DNP-released respiration were inhibited by chlordane compounds, with the ranked degree of inhibition was in descending order being, trans-chlordane, cis-chlordane, and heptachlor. The inhibitory effects of chlordane were more remarkable in the presence of succinate as a respiratory substrate than in the presence of β-hydroxybutylate or ascorbate. Heptachlor also decreased cytochrome C reduction by NADH-cytochrome C reductase. The results suggest that chlordane does not seem to be a specific inhibitor such as cyanide, rotenone, or antimycin A. en-copyright= kn-copyright= en-aut-name=IzushiFumio en-aut-sei=Izushi en-aut-mei=Fumio kn-aut-name=出石文男 kn-aut-sei=出石 kn-aut-mei=文男 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学講座 en-keyword=Chlordane kn-keyword=Chlordane en-keyword=Mitochondria kn-keyword=Mitochondria en-keyword=Oxidative phosphorylation kn-keyword=Oxidative phosphorylation en-keyword=Electron transport system kn-keyword=Electron transport system END start-ver=1.4 cd-journal=joma no-vol=102 cd-vols= no-issue=7-8 article-no= start-page=989 end-page=996 dt-received= dt-revised= dt-accepted= dt-pub-year=1990 dt-pub=199008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Toxicity of organic phosphates and chloronaphthalenes Part 1. The effect on mitochondrial oxidative phosphorylation in the rat liver kn-title=白アリ防除剤に関する実験的研究 第1編 有機リン系薬剤およびクロロナフタリン系薬剤のラット肝ミトコンドリアの酸化的リン酸化に対する作用について en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effect of organic phosphates and chloronaphthalenes, which are used in new pesticides on mitochondrial oxidative phosphorylation in the rat liver was examined. Chlorpyrifos and phoxim decreased State 3 respiration in a dose-dependent manner, but pyridaphenthion, α-and β-chloronaphthalene had only a slight effect. Degree of their effect in the order of chlorpyrifos > phoxim > β-chloronaphthalene > α-chloronaphthalene > pyridaphenthion. Chlorpyrifos, pyridaphenthion, α-and β-chloronaphthalene affected on the State 4 respiration, but phoxim did not. Consequently, they lowered the respiratory control index and the effect being in the order of chlorpyrifos > β-chloronaphthalene > phoxim > α-chloronaphthalene > pyridaphenthion. All the compounds tested stimulated latent ATPase activities, but DNP - stimulated ATPase activities were not affected by these compounds. Their effect on latent ATPase activities were in the descending order of chlorpyrifos > phoxim, β-chloronaphthalene > α chloronaphthalene > pyridaphenthion. These findings suggest that chlorypyrifos, pyridaphenthion, phoxim, α-chloronaphthalene and β-chloronaphthalene impede mitochondrial oxidative phosphorylation. en-copyright= kn-copyright= en-aut-name=SakaiRitsue en-aut-sei=Sakai en-aut-mei=Ritsue kn-aut-name=酒井律江 kn-aut-sei=酒井 kn-aut-mei=律江 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 en-keyword=有機リン系薬剤 kn-keyword=有機リン系薬剤 en-keyword=クロロナフタリン系薬剤 kn-keyword=クロロナフタリン系薬剤 en-keyword=ミトコンドリア kn-keyword=ミトコンドリア en-keyword=酸化的リン酸化 kn-keyword=酸化的リン酸化 END start-ver=1.4 cd-journal=joma no-vol=102 cd-vols= no-issue=5-6 article-no= start-page=779 end-page=788 dt-received= dt-revised= dt-accepted= dt-pub-year=1990 dt-pub=199006 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Study of mitochondrial activity (Rhodamine 123 uptake) on Ehrlich ascites tumor cells and its adriamycin resistant cells kn-title=Ehrlich腹水癌細胞およびAdriamycin耐性細胞のRhodamine 123 uptakeを指標としたミトコンドリア活性 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The positively charged fluorescent dye Rhodamine 123 (Rho 123) accumulates in mitochondria. An adriamycin (ADR)-resistant cell line derived from Ehrlich ascites tumor cells (wild EATC) was established in our laboratory. Overall mitochondrial activity of wild EATC and ADR-resistant EATC was investigated by the staining method with Rho 123. The uptake of Rho 123 into living cells was analyzed by flow cytometry. The intracellular Rho 123 uptake of ADR-resistant EATC was lower than that of wild EATC. The intracellular Rho 123 uptake of wild EATC increased when cells were treated with cepharanthine (CP). The intracellular Rho 123 uptake of ADR-resistant EATC increased markedly by CP treatment. ADR-resistant EATC cosumed more endogenous oxygen than wild EATC. The energy level of ADR-resistant EATC was discussed. en-copyright= kn-copyright= en-aut-name=OkazakiYoshio en-aut-sei=Okazaki en-aut-mei=Yoshio kn-aut-name=岡崎良夫 kn-aut-sei=岡崎 kn-aut-mei=良夫 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部放射線医学教室 en-keyword=アドリアマイシン (ADR) kn-keyword=アドリアマイシン (ADR) en-keyword=ADR耐性細胞 kn-keyword=ADR耐性細胞 en-keyword=ミトコンドリア kn-keyword=ミトコンドリア en-keyword=Rhodamine 123 kn-keyword=Rhodamine 123 en-keyword=ハイパーサーミア kn-keyword=ハイパーサーミア END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=4 article-no= start-page=355 end-page=366 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=20020725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Morphological features of lipid droplet transition during porcine oocyte fertilisation and early embryonic development to blastocyst in vivo and in vitro en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Lipid content in mammalian oocytes or embryos differs among species, with bovine and porcine oocytes and embryos showing large cytoplasmic droplets. These droplets are considered to play important roles in energy metabolism during oocyte maturation, fertilisation and early embryonic development, and also in the freezing ability of oocytes or embryos; however, their detailed distribution or function is not well understood. In the present study, changes in the distribution and morphology of porcine lipid droplets during in vivo and in vitro fertilisation, in contrast to parthenogenetic oocyte activation, as well as during their development to blastocyst stage, were evaluated by transmission electron microscopy (TEM). The analysis of semi-thin and ultra-thin sections by TEM showed conspicuous, large, electron-dense lipid droplets, sometimes associated with mitochondrial aggregates in the oocytes, irrespective of whether the oocytes had been matured in vivo or in vitro. Immediately after sperm penetration, the electron density of the lipid droplets was lost in both the in vivo and in vitro oocytes, the reduction being most evident in the oocytes developed in vitro. Density was restored in the pronculear oocytes, fully in the in vivo specimens but only partially in the in vitro ones. The number and size of the droplets seemed, however, to have decreased. At 2- to 4-cell and blastocyst stages, the features of the lipid droplets were almost the same as those of pronuclear oocytes, showing a homogeneous or saturated density in the in vivo embryos but a marbled or partially saturated appearance in the in vitro embryos. In vitro matured oocytes undergoing parthenogenesis had lipid droplets that resembled those of fertilised oocytes until the pronuclear stage. Overall, results indicate variations in both the morphology and amount of cytoplasmic lipid droplets during porcine oocyte maturation, fertilisation and early embryo development as well as differences between in vivo and in vitro development, suggesting both different energy status during preimplantation development in pigs and substantial differences between in vitro and in vivo development.

en-copyright= kn-copyright= en-aut-name=KikuchiKazuhiro en-aut-sei=Kikuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EkwallHans en-aut-sei=Ekwall en-aut-mei=Hans kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TienthaiPaisan en-aut-sei=Tienthai en-aut-mei=Paisan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaiYasuhiro en-aut-sei=Kawai en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NoguchiJunko en-aut-sei=Noguchi en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KanekoHiroyuki en-aut-sei=Kaneko en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Rpdriguez-MartinezHeriberto en-aut-sei=Rpdriguez-Martinez en-aut-mei=Heriberto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil=Swedish University of Agricultural Sciences affil-num=2 en-affil= kn-affil=Swedish University of Agricultural Sciences affil-num=3 en-affil= kn-affil=Swedish University of Agricultural Sciences affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=National Institute of Agrobiological Sciences affil-num=6 en-affil= kn-affil=National Institute of Agrobiological Sciences affil-num=7 en-affil= kn-affil=Swedish University of Agricultural Sciences en-keyword=Culture kn-keyword=Culture en-keyword=In vitro kn-keyword=In vitro en-keyword=In vivo kn-keyword=In vivo en-keyword=Lipid droplet kn-keyword=Lipid droplet en-keyword=Pig kn-keyword=Pig END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=1 article-no= start-page=11 end-page=18 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=201002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Comparison of Capillary Architecture between Slow and Fast Muscles in Rats Using a Confocal Laser Scanning Microscope en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The skeletal muscle is classified into 2 types, slow oxidative or fast glycolytic muscle. For further characterization, we investigated the capillary architecture in slow and fast muscles. The rat soleus and extensor digitorum longus (EDL) muscles were used as representatives of slow and fast muscles, respectively. To investigate capillary density, sections of both types of muscle were stained with alkaline phosphatase;the soleus muscle showed more intense reactivity, indicating that it had a denser capillary structure than the EDL muscle. We then injected fluorescent contrast medium into samples of both muscle types for light and confocal-laser microscopic evaluation. The capillary density and capillary-to-fiber ratio were significantly higher, and the course of the capillaries was more tortuous, in the soleus muscle than in the EDL muscle. Capillary coursed more tortuously in the soleus than in the EDL muscle. Succinate dehydrogenase (SDH) activity, an indicator of mitochondrial oxidative capacity, and vascular endothelial growth factor (VEGF) expression were also significantly higher in the soleus muscle. Thus, we conclude that slow oxidative muscle possess a rich capillary structure to provide demanded oxygen, and VEGF might be involved in the formation and/or maintenance of this highly capillarized architecture.

en-copyright= kn-copyright= en-aut-name=MurakamiShinichiro en-aut-sei=Murakami en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujinoHidemi en-aut-sei=Fujino en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakedaIsao en-aut-sei=Takeda en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MomotaRyusuke en-aut-sei=Momota en-aut-mei=Ryusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KumagishiKanae en-aut-sei=Kumagishi en-aut-mei=Kanae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences affil-num=3 en-affil= kn-affil=Department of Physical Therapy, Himeji Dokkyo University affil-num=4 en-affil= kn-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=skeletal muscle kn-keyword=skeletal muscle en-keyword=capillaly kn-keyword=capillaly en-keyword=succinate dehydrogenase activity kn-keyword=succinate dehydrogenase activity en-keyword=vascular endothelial growth factor kn-keyword=vascular endothelial growth factor END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=1 end-page=13 dt-received= dt-revised= dt-accepted= dt-pub-year=1970 dt-pub=197002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reduction of a disulphide in relation to the metabolic states of mitochondria en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The role of -SH groups in mitochondrial energy transfer reaction was studied by observing the reduction of a disulphide, 5, 5'-dithiobis (2-nitrobenzoic acid), DTNB, a specific analytical agent for the estimation of -SH groups in biological materials, by addition of it to the isolated rat liver mitochondria in various respiratory states, as defined by CHANCE and WILLIAMS. 1. In the various respiratory states, states 1 to 5, the reduction of DTNB proceeds most rapidly at state 5, and most slowly at state 3. DTNB reduction at state 5 is suppressed by the partial oxidation of respiratory carriers with oxygen (state 4) and the addition of respiratory substrate does not affect the DTNB reduction. 2. The retardation in the reduction rate at state 3 is relieved partially by a respiratory inhibitor, KCN, and is intensified markedly by oligomycin, an inhibitor of oxidative phosphorylation. An uncoupler for oxidative phosphorylation, DNP, does not affect the reduction rate at state 3. At state 4 the reduction is stimulated by DNP and KCN, but is unaffected by oligomycin. The results suggest that the alteration in the functions of the energy transfer reaction in mitochondria is accompanied by changes in the occurrence and the functioning of -SH groups which can be detected by the reactivity with DTNB. The data suggest also that there are at least two kinds of -SH groups reacting with DTNB: the one is the -SH group which reacts DTNB actively when the respiratory carriers are kept reduced, and the other is the one which reacts actively when the respiratory carriers are kept oxidized, participating in the phosphorylating system and its reactivity with DTNB diminishes in the actively phosphorylating states (states 2 and 3).

en-copyright= kn-copyright= en-aut-name=MiyaharaMasanobu en-aut-sei=Miyahara en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=1 article-no= start-page=49 end-page=64 dt-received= dt-revised= dt-accepted= dt-pub-year=1970 dt-pub=197002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Activation and isolation of mitochondrial adenosine triphosphatase by ultrasonic irradiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=

With the purpose to clarified the mode of localization and mechanisms of activation of ATPase in the mitochondrial membrane, analyses were made on the properties of mitochondrial ATPase from the structural and functional aspects. The activation of ATPase by DNP and Mg++ and the oligomycin sensitivity were investigated in a series of inner membrane fragment samples obtained by ultrasonic irradiation and those samples obtained in the processes of isolation and purification of ATPase from rat liver mitochondria and beef heart mitochondria in parallel with electron microscope observations. As a result it has been found that the membrane fragments obtained from rat liver and beef heart mitochondria by ultrasonication exhibited high respiratory activity and unmasked ATPase activity which was charac? terized by remarkable stimulation by Mg++ and inhibition by oligomycin and azide. Therefore, mitochondrial ATPase seems to be bound fairly closely to the inner mitochondrial membrane. In the membrane fragments prepared by ultrasonication of intact mitochondria, ATPase activity was stimulated by DNP, but in the supernatant fractions was not. On the other hand, the supernatant fraction obtained from BHM and inner membrane fragments by severe sonication exhibits a marked ATPase activity and the activity incresed in each step of the purification on the treatments with acid, protamine and heat. Especially in the case of membrane fragments the protamine treatment can be omitted. Electron microscope observation of the fractions in each step of the purification proved the head pieces to be ATPase. The ATPase activity of solubilized head pieces is insensitive to oligo. mycin and coincides with the soluble ATPase of PULLMAN etat. (8) in the points of its cold labile property and optimum pH, but it shown no accele. ration of ATPase activity by DNP.

en-copyright= kn-copyright= en-aut-name=YamamotoGoki en-aut-sei=Yamamoto en-aut-mei=Goki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukamotoHiromichi en-aut-sei=Tsukamoto en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=3 article-no= start-page=287 end-page=302 dt-received= dt-revised= dt-accepted= dt-pub-year=1970 dt-pub=197006 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on nucleic acids in Rous sarcoma virus-induced mouse ascites sarcoma cells. Distribution and electron microscopy of nucleic acids in subcellular fractions and circular DNA in mitochondrial fraction en-subtitle= kn-subtitle= en-abstract= kn-abstract=

For the purpose to clarify the distribution of DNA in mouse ascites sarcoma cells (SR-C3H) induced by Rous sarcoma virus (Schmidt-Ruppin strain), quantitative assays were carried out by SCHMIDT-THANNHAUSERSCHNEIDER'S method using subcellular fractions isolated from SR-C3H cells and C3H mouse liver as a control tissue, and simultaneously electron microscopic observations were conducted with the rotary shadowed preparations of the SDS-phenol extracted nucleic acids by the protein monolayer technique. The results are briefly summarized as follows. 1. The RNA/DNA ratios in SR-C3H cells and liver cells were 2.3 and 3.7, while those in nuclear fraction of SR-C3H cells and liver cells were 0.34 and O. 56, respectively. The electron micrographs of nuclear nucleic acids revealed a DNA-RNA complex-like structure. 2. DNA and RNA contents of SR-C3H mitochondria were found to be 3.1 and 24 fl-g per mg of protein, respectiVely, which proved to be greater than those of liver mitochondria. The mean values of the contour length of circular DNA molecules in highest frequency group observed in the electron micrographs were 4.88 μ. in SR-C3H mitochondria and 5.08 μ. in mouse liver mitochondria. There could be observed circular molecules of duplicated-length in both mitochondrial DNA's and small circular molecules in SR-C3H mitochondrial DNA. 3. In the microsomal and supernatant fractions of SR-C3H cells and mouse liver cells, the ratios of DNA to RNA gave several percent by chemical analysis and this percentage was particularly high in the supernatant of SR-C3H cells. On the other hand, in the electron micrographs, the fibrous structure was significantly recovered in the supernatant nucleic acids of SR-C3H cells, but with difficulty in the other three fractions. This fibrous structure measured 1.13 μ in the mean value of the length and was considered to be DNA as it readily disappeared after the treat? ment with DNase.

en-copyright= kn-copyright= en-aut-name=YamamotoGoki en-aut-sei=Yamamoto en-aut-mei=Goki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=2 article-no= start-page=143 end-page=159 dt-received= dt-revised= dt-accepted= dt-pub-year=1970 dt-pub=197004 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Isolation and some properties of oligomycin-sensitive adenosine triphosphatase from beef heart mitochondria and its morphological study en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. To have a rapid isolation of oligomycin-sensitive ATPase particles (OSA particles), 0.1 mg DOC per mg of protein and 72 g potassium chlo. ride per I were added to mitochondria suspended in a tris.sucrose-histidine solution, which was followed by addition of 2-fold volume of chilled water, and fractionated by a discontinuous sucrose density gradient centrifugation. As a result, it was possible to reveal the OSA particle structure, composed of the head piece, stalk and thread-like structure of a superficial portion of the base pieces, stripped off from the mitochondrial inner membrane, in a layer of density.l.lO. This fraction exhibited a remarkable activity of ATPase sensitive to oligomycin, approximately 15 ,lJ.moles Pi released per mg of protein per minute at pH 8.6 at 37° in a non-ATP regenerating assay system, and contained almost no cytochromes. 2. When the OSA particles thus isolated were heated in water bath at 65° for 2 minutes, the head pieces were detached with a concomitant loss of oligomycin-sensitivity and were purified from the supernatant by precipitation with ammonium sulfate. 3. Trypsin in low concentration slightly induced a rise in the ATPase activity of OSA particles but in higher concentration it inhibited the activity. 4. OSA particles were resistant to the treatment of urea, and it was difficult to detach the head pieces by this treatment. 5. The some fraction obtained by solubilization of thc crude OSA particles with cholate and fractionation with ammonium sulfate exhibited ATPase activity in a masked form, and the ATPase activity with oligomycin. sensitivity was restored on addition of phospholipid. 6. A discussion was made on the mode of assembly of the head pieces and associated components and biochemical properties of OSA particles.

en-copyright= kn-copyright= en-aut-name=YamamotoGoki en-aut-sei=Yamamoto en-aut-mei=Goki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=6 article-no= start-page=551 end-page=557 dt-received= dt-revised= dt-accepted= dt-pub-year=1970 dt-pub=197012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial DNA from hamster tumors induced by adenovirus type 12 en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. Mitochondria isolated from hamster tumors induced by adenovirus type 12 possessed circular DNA fibers. 2. The mean value of the length of the highest frequency group of the circular DNA molecules was 4.92 ±0.38 μ. 3. Catenated dimer DNA molecules and small (less than 2 μ in length) circular DNA molecules were observed.

en-copyright= kn-copyright= en-aut-name=NishidaShigeru en-aut-sei=Nishida en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=24 cd-vols= no-issue=4 article-no= start-page=405 end-page=415 dt-received= dt-revised= dt-accepted= dt-pub-year=1970 dt-pub=197008 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Circular DNA's from HeLa cell nuclei and mitochondria en-subtitle= kn-subtitle= en-abstract= kn-abstract=

An electron microscopic observation was made on the DNA's extracted from purified HeLa cell nuclei, mitochondria, and the whole cell, and fractionated by ethidium bromide-cesium chloride density gradient method or sucrose density gradient method. Nuclear DNA presents mainly long linear DNA derived from fragmented chromosomal DNA. In addition to this, the existence of small circular DNA molecules measuring 0.32 -1.78 μ, was confirmed. Mitochondrial DNA was mainly circular DNA, which measured 4.87 μ in the mean value of the contour lengths in the highest frequency group, and small circular DNA molecules, measuring 0.3-1.01 μ in contour length, were also found in an extremely low frequency.

en-copyright= kn-copyright= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OmuraSachiko en-aut-sei=Omura en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoShinichiro en-aut-sei=Yamamoto en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishidaShigeru en-aut-sei=Nishida en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HirataSeiichi en-aut-sei=Hirata en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=6 article-no= start-page=259 end-page=271 dt-received= dt-revised= dt-accepted= dt-pub-year=1963 dt-pub=1963 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relation between mitochondrial swelling induced by inorganic phosphate and accumulation of P³² in mitochondrial Pi fraction en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. Rat liver mitochondria are swollen by inorganic phosphate in the medium of slightly hypotonic sucrose solution containing respiratory substrate and the mitochondrial swelling is inhibited or turned to shrink by ADP, respiratory inhibitor, anaerobiosis and uncoupler of oxidative phosphorylation. This mitochondrial swelling is not inhibited by the inhibitor of phosphorylating respiration such as oligomycin and tributyltin chloride. 2. Rat liver mitochondria are swollen by ATP in the presence of antimycin A, inorganic phosphate and 0.1 mM of CaCl2 and such a swelling is inhibited by oligomycin. 3. Accumulation of a small amont of P³² in acid soluble Pi fraction of rat liver mitochondria proceeds even in the medium containing neither ATP nor Ca++ but is inhibited by respiratory inhibitor, ATP, ADP and uncoupler of oxidative phosphorylation. The accumulation of P³² in mitochondria, however, is not inhibited by oligomycin. 4. The accumulation of P³² is induced by ATP in the presence of antimycin A and Ca++(O.l mM) and such an accumulation of P³² is inhibited by oligomycin. 5. It is suggested that the Pi-induced swelling of mitochondria is correlated to the accumulation of inorganic phosphate and both of them are tightly coupled to the initial step in the process of oxidative phosphoryaltion.

en-copyright= kn-copyright= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=2 article-no= start-page=101 end-page=112 dt-received= dt-revised= dt-accepted= dt-pub-year=1968 dt-pub=196804 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nucleic acids and protein synthesis in cancer cell mitochondria. II. Amino acid incorporation into proteins of rat liver and hepatoma cell mitochondria en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The energy source required for the amino acid incorporation into mitochondrial proteins has been investigated and comparative study has also been made on the rate of the amino acid incorporation in rat liver and rat hepatoma cell mitochondria. 1. The incorporation of amino acid into the protein in intact mitochondria of rat liver increased by about 40% on the addition of α-ketoglutarate and ADP, but no significant increase in the amino acid incorporation was observed on the addition of succinate and ADP. 2. The incorporation of amino acids into mitochondrial proteins was remarkably inhibited by the addition of respiratory inhibitors (cyanide, DNP at a high concentration). 3. The amino acid incorporation into mitochondrial proteins was scarcely or slightly inhibited by the addition of DNP at the concentration of 1×10-4M and insensitive to oligomycin (5 to 10 μg/ml). 4. The amino acid incorporation into the protein in the endogenous substrate system of the mitochondria was considerably inhibited by the addition of arsenite, and this inhibition somewhat recovered on the addition of ADP plus succinate. 5. The rate of the amino acid incorporations between rat liver and hepatoma cell mitochondria was at the same level. 6. Discussions were made on the energy source required for the amino acid incorporation into mitochondrial proteins, on the rate of protein synthesis per mitochondrion isolated from rat liver- and hepatoma cells, and on the possibilities of contamination of bacteria or microsomes and of the adsorption of amino acids onto the mitochondria.

en-copyright= kn-copyright= en-aut-name=InabaKozo en-aut-sei=Inaba en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=4 article-no= start-page=175 end-page=184 dt-received= dt-revised= dt-accepted= dt-pub-year=1968 dt-pub=196808 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Purification of the head-pieces of the elementary particles from beef heart mitochondria: their morphological structure and enzymatic activity en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. In order to obtain direct evidence for the enzymatic identification of the head-pieces of the elementary particles in the inner mitochondrial membrane, the head-pieces were detached by sonication from the isolated inner membrane of beef heart mitochondria, purified by pursuing the particles with the electron microscope, and analyzed for enzymatic properties. 2. Electron microscope examination revealed that the isolated headpieces are the spherical particles about 90À in diameter which are quite similar in appearance to the head-pieces of the elementary particles lining the inner mitochondrial membranes. 3. The head-pieces are identified as ATPase sensitive to oligomysin when attached by stalks to the membrane, and become insensitive when detached or purified from the membrane. 4. The head-piece is labile to cold with respect to ATPase activity and morphology.

en-copyright= kn-copyright= en-aut-name=KoshibaK. en-aut-sei=Koshiba en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoG. en-aut-sei=Yamamoto en-aut-mei=G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoharaR. en-aut-sei=Inohara en-aut-mei=R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OdaT. en-aut-sei=Oda en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=13 end-page=20 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=196902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distribution of tumor antigen in cell fractions of adenovirus 12-induced tumor--its application to fluorescent antibody technique en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Adl2-induced tumors were homogenized and fractionated by the SCHNEIDER'S method. The CF test with the serum from tumor-bearing hamsters revealed the predominant presence of T-antigen in the mitochondrial and microsomal fractions. Hence, the rabbit was immunized with the microsomal fraction of tumors, and its serum was used to prepare the fluorescent antibody to T-antigen. The direct staining of the tumor cells with so prepared fluorescent antibody gave a staining pattern similar to the indirect staining with the serum of tumor-bearing hamsters. It thus appeares possible to stain T-antigen by the direct immunofluorescent method using the serum of rabbits hyperimmunized with the microsomal fraction of Ad12-induced tumors.

en-copyright= kn-copyright= en-aut-name=OkamotoTsukasa en-aut-sei=Okamoto en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=1 article-no= start-page=47 end-page=68 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=196902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunological studies on the membrane systems of cancer cells. II. Immunochemical specificity of the mitochondria from chemical carcinogen induced carcinoma cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=

As the results of investigating the antigenicities of various fractions from the membrane systems of cancer cells, it has been found that the remarkable cancer-specific antigenicity exists in cancer cell mitochondria. With a particular reference to this antigenicity of cancer cell mitochondria, the antigenicities of the mitochondria of various kinds of rat ascites tumors and those of tumor-bearing rat liver mitochondria have been compared with those of normal rat liver mitochondria. In addition, it has been demonstrated that a strong tumor antitransplantability is induced when the recipient rat is immunized with the tumor cell mitochondria. In order to support these experimental facts, enzymatic activities of cancer cell mitochondria have been investigated also biochemically after treating the mitochondria with the antiserum to these mitochondria. 1. The most remarkable cancer specific antigenicity exists in mitochondria among the membrane systems of cancer cells. This cancer mitochondria-specific cancer antigenicity is common to all the ascites tumor mitochondria used here. 2. The original tissue- or organ-specific antigenicities diminish or disappear at the carcinogenic transformation of cells. 3. The tumor-bearing-organ specific antigenicity appears in the organs of animals bearing tumor. 4. The tumor antitransplantability is acquired when rats are immunized with these tumor cell mitochondria. 5. The inhibition of mitochondrial ATP?ase and respiratory activities is observed when the cancer cell mitochondria are treated with the anti. serum to the mitochondria.

en-copyright= kn-copyright= en-aut-name=WakabayashiAkira en-aut-sei=Wakabayashi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=3 article-no= start-page=237 end-page=255 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=196906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on the reconstitution of the structure and function of mitochondrial inner membrane. I. Structure and function of the membrane formed by the purified complex 3 and complex IV of the mitochondrial electron transfer chain en-subtitle= kn-subtitle= en-abstract= kn-abstract=

In order to elucidate the molecular organization of mitochondrial inner membrane, biochemical and electron microscope observations were made on the formation of membrane structure and function by the purified complexes of the electron transfer chain of beef heart mitochondria. Purified complex III (CoQ-cytochrome c reductase) and complex IV (cytochrome oxidase) were soluble in the presence of bile salts. They were, however, aggregated to form membrane by washing out the bile salts. When the membranous complexes III and IV were mixed, both membranes were separate by density gradient centrifugation and the vesicle which contained both complexes could not be formed and CoQH2-oxidase activity was hardly re;tored. When the mixture of the solubilized complexes III and IV were diluted to remove the bile salts, a membranous vesicle in which both complexes were assembled was formed. CoQH2-oxidase activity was restored in accordance with the formation of the membrane. The membrane which contained any desired propotion of each complexes could be obtained. These facts indicate that the complexes of the electron transfer chain conjugate two-dimentionally each other and form the membrane to carry electrons from substrate to oxygen most efficiently.

en-copyright= kn-copyright= en-aut-name=HayashiHideo en-aut-sei=Hayashi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=3 article-no= start-page=227 end-page=235 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=196906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The competitive effect of adenosine-5'-triphosphate against the stimulating and inhibiting actions of 2,4-dinitrophenol on the mitochondrial respiration en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Effect of ATP and substrates on 2,4-dinitrophenol-induced adenosine triphcsphatase (E. C. 3.6. 1. 4.) activity and respiration of isolated rat liver mitochondria has been investigated. 1. The oxidation of sodium succinate inhibited the action of 2, 4-DNP on the induction of adenosine triphosphatase activity in the mitochondria. 2. A moderately large amount of sodium succinate restored the suppressed mitochondrial respiration due to 2, 4-DNP. 3. Adenosine-5'-triphosphate (ATP) restored quantitatively the released and inhibited mitochondrial respiration due to 2,4-DNP, and its prior addition prevented also quantitatively the action of 2,4-DNP on the mitochondrial oxygen up-take. These ATP effects were oligomycin sensitive, and they were considered to manifest their actions through the phosphorylation system.

en-copyright= kn-copyright= en-aut-name=HataseO. en-aut-sei=Hatase en-aut-mei=O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoG. en-aut-sei=Yamamoto en-aut-mei=G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OdaT. en-aut-sei=Oda en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=5 article-no= start-page=393 end-page=411 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=196910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tissue typing by mixed culture of lymphocytes. I. Demonstration of intracellular localization of transplantation antigen and H-2 antigen differences by the mixed cultures with addition of whole homogenate or ultracentrifuged fractions of mouse lymph-node cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. The cells used in the present experiments were lymph-node cells from inbred mice, and over 98 % cells were proven to be small lympho-cytes. Therefore, those cells that have undergone blastformation are all those derived from small lymphocytes. 2. When homogenate of one cell group is cultured with live cells of the other pairing group, there occurs blastformation. In the presence of PHA, such a blastformation becomes more marked. 3. The optimal concentration of PHA (phytohemagglutinin)-M added to the mixed culture is found to be 1% (v/v). 4. The maximum rate of blastformation in the mixed culture is observed at the culture hour 48, being much faster than in the mixed culture between two live cell groups. 5. In the mixed cultures between subcellular fractions prepared from cell homogenate by centrifugation and live cells, the transplantation antigenic potential (histocompatibility antigenic potential) is seen in the mitochondrial and the microsomal fractions, especially marked in the latter. 6. In the observations carried out by various combinations of these inbred mice, it has been demonstrated that the rate of blastformation induced by the addition of cell homogenate or sediment fractions prepared from the homogenate reflects quite accurately the differences in H-2 antigens.

en-copyright= kn-copyright= en-aut-name=MiwaHiroaki en-aut-sei=Miwa en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=5 article-no= start-page=343 end-page=356 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=196910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ultrastructure and biochemical function of the mitochondria in respiratory-deficient mutant yeast induced by 4-nitroquinoline nitrogen oxide en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. A respiratory-deficient mutant strain of yeast was obtained from wild strain of Saccharomyces servisiae by treatment with 4-nitroquinoline N-oxide. Ultrastructure and function of the wild or mutant strains and the mitochondrial fractions isolated from these strains were examined by biochemical and electron microscopic analyses. 2. The frequency of the respiratory-deficient mutant strain in yeast induced with 10-6M 4-nitroquinoline N-oxide was about 40 %. 3. Respiratory-deficient mutant strain is incapable of reducing 2, 3, 5-triphenyltetrazolium chloride salt and to grow on lactate medium. In addition to this, the mutant has been found to have lost its ability to take up oxygen in sodium succinate and pyruvate. 4. 4.Nitroquinoline N-oxide in the concentration that induces a mutant of yeast cells or its kin inhibits the oxygen uptake in normal strain. 5. The normal strain of yeast is characterized by difference spectrum corresponding to cytochromes a+as, band c+Cll respectively, whereas, the mutant strain containes almost no cytochromes a+ as, band C1 but contains normal or increased amount of cytochrome c. 6. Mitochondrial fraction isolated from mutant strain has largely lost its ability to oxidize succinate. On the other hand, NADH-, lactate-and cytochrome c-oxidase activities are reduced by about 1/17, 1/7 and 1/8 of that of normal strain, respectively. 7. Succinate dehydrogenase activity of mutant strain is almost zero. Moreover, this activity is not affected on the addition of phenazine methosulfate. NADH dehydrogenase activity of mutant stran is about 1/2 of normal strain. 8. The variations in mitochondrial structure of normal and mutant strain in the stationary phase have been followed with the aid of electron microscopy. In contrast to the normal strain, the mutant strain revealed distinct morphological changes in mitochondria, especially, the lack of cristae in its interior. The results have been interpreted to indicate that the mutant induced by 4.nitroquinoline N.oxide has a character of cyto. plasmic mutant.

en-copyright= kn-copyright= en-aut-name=KoshibaKimikazu en-aut-sei=Koshiba en-aut-mei=Kimikazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsukamotoHiromichi en-aut-sei=Tsukamoto en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotoNobuyuki en-aut-sei=Goto en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=2 article-no= start-page=105 end-page=124 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=196904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immunological studies on the membrane systems of cancer cells. 3. Immunospecificities of the mitochondria from virus-induced tumors by the precipitin reaction in agar gel en-subtitle= kn-subtitle= en-abstract= kn-abstract=

<P>The mitochondrial, the microsomal, and the supernatant fractions were prepared from the cell homogenate of tumors induced by viruses, such as adenovirus type 12, SV 40, and Rous sarcoma virus, etc. and the antigenicities of these fractions were investigated. In the virus-induced tumors, there existed no antigenicity common to the mitochondrial and the microsomal fractions as in the tumors induced by chemical carcinogens, and the highest antigenicity was recognized in the mitochondrial fraction. Therefore, the properties of the tumor cell mitochondria were precisely investigated with virus-induced tumor mitochondria. 1. The mitochondria of tumors induced by viruses have clearly the specific antigenicity. 2. This specific antigenicity of virus.induced tumor mitochondria IS common to all the virus-induced tumors used in the present study. 3. This tumor mitochondria.specific antigenicity is found commonly in all the tumor mitochondria in the present experiments. 4. The specific cancer antigenicity of tumor cell mitochondria does not exist in normal organ mitochondria, but the regenerating organ mitochondria exhibit a slight antigenicity common to cancer cell mitochondria.

en-copyright= kn-copyright= en-aut-name=WakabayashiAkira en-aut-sei=Wakabayashi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=6 article-no= start-page=465 end-page=479 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=196912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=DNA's from human hepatoma and gastric cancer mitochondria en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. Mitochondria isolated from human liver, hepatoma and gastric cancer contain DNA. The DNA content per mitochondrial protein is about ten times as much in cancer as in normal liver. 2. Human liver, hepatoma and gastric cancer contain circular DNA molecules in their mitochondria. Circular DNAs from normal liver and cancer mitochondria are mostly about 5 μ long, and the frequency of circular DNAs of multiple or shorter length is higher in cancer mitochondrial DNA. The outline of the present paper was presented at the 26th Congress of Japanese Cancer Association (1967) (52, 53).

en-copyright= kn-copyright= en-aut-name=TakeSatoru en-aut-sei=Take en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=4 article-no= start-page=303 end-page=322 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=196908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on the reconstitution of the structure and function of the mitochondrial inner membrane. II. Dissolution and reconstitution of the mitochondrial inner membrane en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1) In order to study the molecular structure and electron transfer activities of mitochondrial inner membrane, dissolution and reconstitution of membranous structure and function of the inner membrane of beef heart mitochondria were carried out. 2) The inner membrane of mitochondria could be dissolved into some unit of particles 70-140 Å in diameter by the treatment with bile salts at the concentration 0.5 mg of deoxycholate per mg of protein, 0.5 mg of cholate per mg of protein and 74.5 mg of crystalline potassium chloride per ml of the suspension. 3) The dissolved unit particles readily reaggregated into a vesicular membrane simultaneously restoring over-all electron transfer activities by the removal of bile salts with dilution of the suspension.4) Isolated electron transfer unit particle fraction contammg all components of the electron transfer chain but no structural protein were soluble in aqueous solution due to some residual bile salts used in the preparation. The removal of bile salts by dilution led the dispersed particles to aggregate into membrane and restore their over-all enzymatic activities. 5) From these results and the results of the reconstitution of membrane from purified complexes as described in the previous paper, it may be concluded as follows: The mitochondrial inner membrane may consist of several kinds of repeating unit particles conjugating each other with adjacent particles. It is necessary for over?all enzymatic activities that some unit components aggregate into a single vesicular membrane. Structural proteins may play an important role in the constitution of the membranous structure and in the over-all enzymatic activities.

en-copyright= kn-copyright= en-aut-name=HayashiHideo en-aut-sei=Hayashi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=2 article-no= start-page=79 end-page=89 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=196704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Purification and fine structure of reduced coenzyme Q-cytochrome C reductase in the mitochondrial membrane en-subtitle= kn-subtitle= en-abstract= kn-abstract=

For the purpose of revealing the molecular organization of the mitochondrial membrane the authors attempted to clarify the fine structure of reduced coenzyme Q-cytochrome c reductase and also studied how the CoQH2-cyt. c reductase is arranged in the mitochondrial membrane by systematic analyses of fractions from the purification process of CoQH2-cyt. c reductase. 1. Purified CoQH2-cyt. c reductase contained high concentration of cyt. b (9.5 mμmoles per mg protein) and cyt. Cl (4.5 mμmoles per mg protein), and was almost free from cyt. c, a, flavoproteins, primary dehydrogenases and ATPase. The enzyme complex also showed a high specific activity (48 μmoles of cyt. c reduced per mg protein per min at 30°). 2. CoQH2-cyt. c reductase was composed of particles of about 120 Å in diameter with irregular form, some time exhibiting electron opaque cores. In the loose aggregates of the particles, the size of each particle was about 95 Å in diameter. 3. An intimate correlation was observed between the particles of CoQH2cyt. c reductase and those on the surface of the NADH-cyt. c reductase fraction. 4. Regular arrays of uniform particles (about 82 Å in diameter with a center to center distance of about 100 Å) were observed on the surface of the submitochondrial membrane (brown membrane) obtained from beef heart mitochondria by treatment with deoxycholate (0.1 mg / mg protein) and KCl (72 g/l). The correlation between these particles and CoQH2-cyt. c reductase was discussed.

en-copyright= kn-copyright= en-aut-name=SekiShuji en-aut-sei=Seki en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HataseOsamu en-aut-sei=Hatase en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=6 article-no= start-page=297 end-page=313 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=196712 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nucleic acids and protein synthesis in cancer cell mitochondria. I. Nucleic acids in rat hepatoma mitochondria en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The contents of nucleic acids in rat liver and hepatoma mitochondria and the physico-chemical properties on DNA's isolated from these mitochondria were comparatively investigated. The results are briefly summarized as follows. 1. The contents of DNA and RNA per mg protein of the hepatoma cell mitochondria were about 10 and 2 to 4 times higher than those of rat liver mitochondria, respectively. 2. The λ max. and λmin. values of DNA isolated from the hepatoma mitochondria were 257 mμ and 231 mμ, respectively and those of DNA isolated from the nuclei were 259 mμ and 233 mμ, respectively, in saline-citrate, pH 7.0. 3. Three fractions of mitochondrial DNA were obtained by the sucrose density gradient and these DNA fractions corresponded, probably, to about 30 S, and 20 S and 14 S DNA's. 4. There was little difference in base compositions between nuclear and mitochondrial DNA's of the hepatoma cells. 5. The degree of hybridization between the nuclear and mitochondrial DNA's of the hepatoma cells was almost the same as that between the nuclear and nuclear DNA's of the hepatoma cells, and somewhat higher than that between the nuclear DNA of rat liver and the nuclear DNA of hepatoma cells. 6. "Highly twisted" circular, "open" circular and linear forms were observed in the DNA preparations of the hepatoma mitochondria. The average values of contour lengths of rat liver and the hepatoma DNA's observed at high frequency were 5.3 μ and 4.5 μ. 7. A discussion was made on the relation between the genetic informations of mitochondrial DNA and the formation of a mitochondrion in rat liver and the hepatoma cells.

en-copyright= kn-copyright= en-aut-name=InabaKozo en-aut-sei=Inaba en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=4 article-no= start-page=147 end-page=160 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=196708 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Isolation of oligomycin-sensitive adenosine triphosphatase from beef heart mitochondria and analysis of its fine structure en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. An oligomycin -sensitive ATPase was isolated and partially purified from beef heart mitochondria. The specific activity of ATPase sensitive to oligomycin of the fraction was five to eight times that of aged mitochondrial or of DNP-induced mitochondrial ATPase assayed under the same condition. 2. Electron micrographs of the partially purified oligomycin- sensitive ATPase reveal a structure in which headpieces are regularly attached by way of stalks to a thread-like structure derived from a superficial portion of base pieces. 3. A high concentration of the structured material coincided with a high activity of oligomycin-sensitive ATPase. When the headpieces were detached from the structure, the ATPase became insensitive to oligomycin. 4. The fraction of oligomycin -sensitive ATPase was essentially free of membrane structure and was contaminated with a small amount of cytochromes b and Cl but no cyt. a. Cytochrome concentrations of the preparations were indifferent to the activity of oligomycin sensitive ATPase. It follows that ATPase does not require cytochromes or membrane structure for its oligomycin sensitivity. 5. From these results it seems that the factor rendering ATPase sensitive to oligomycin should be contained in the stalks and/or the thread-like portion of basepieces of the structure. The structure is the simplest unit of oligomycinsensitive ATPase as yet obtained. 6. The structure was called "oligomycin-sensitive ATPase particles" (abbreviated as OSA particles). A unit of OSA particles consists of a headpiece attached by a stalk to a portion of base piece.

en-copyright= kn-copyright= en-aut-name=SekiShuji en-aut-sei=Seki en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoGoki en-aut-sei=Yamamoto en-aut-mei=Goki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HayashiHideo en-aut-sei=Hayashi en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoharaRisaburo en-aut-sei=Inohara en-aut-mei=Risaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=4 article-no= start-page=191 end-page=203 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=196708 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Flavin and cytochrome contents in the mitochondria of the heart and liver en-subtitle= kn-subtitle= en-abstract= kn-abstract=

With a certain fixed methods of analyses, we carried out the determination of flavins and cytochromes in the mitochondria (Mt) and electron transfer particles (ETP) of the heart and liver of rats and cows, and made a comparison of the data with one another. Our findings may briefly be summarized as follows. 1. The concentration of each component of the beef heart mitochondria proved to be 0.47 for acid extractable flavins; 0.22 for acid nonextractable flavin; O. 75 for cytochrome (cyt.) a; 0.58 for cyt. b; and O. 51 for cyt. C + Cl, all units being mμ mole per mg of protein. 2. In the beef liver mitochondria it was 0.46 for acid extractable flavins; 0.18 for acid non-extractable flavin; 0.092 for cyt. a; 0.089 for cyt. b; and 0.122 for cyt. C+Cll likewise all units in term of mμ mole per mg of protein. 3. In the case of rat heart mitochondria, it was found to be O. 42 for acid extractable flavins; 0.22 for acid non-extractable flavin; 0.88 for cyt. a; 0.41 for cyt. b; and 0.62 for cyt. C + Cll all in mμ mole per mg of protein. 4. In the rat liver mitochondria it was 0.56 for acid extractable flavins; 0.19 for acid non-extractable flavin; 0.20 for cyt. a; 0.14 for cyt. b; and 0.19 for cyt. C+Cl. 5. The concentration ratios of Fs, cyt. a and cyt. b of the mitochondria, what are considered to be intrinsic and fixed components of the mitochondrion. to those of the electron transfer particles were 1. 3 in both the beef heart and the rat heart, while 2.2 in the beef liver and 2.1 in the rat liver. 6. These findings were compared with the data reported by other workers, and also a discussion was made on the molecular organization of the mitochondrial inner membrane.

en-copyright= kn-copyright= en-aut-name=IwataShinnosuke en-aut-sei=Iwata en-aut-mei=Shinnosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SekiShuji en-aut-sei=Seki en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=1 article-no= start-page=33 end-page=43 dt-received= dt-revised= dt-accepted= dt-pub-year=1964 dt-pub=196402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Uncoupling agent of oxidative phosphorylation from ascitic fluid of tumor bearing mice after X-irradiation en-subtitle= kn-subtitle= en-abstract= kn-abstract=

It was investigated to clarify the relationship between the composition of the lipid fractions obtained from the ascitic fluid of Ehrlich ascites tumor bearing mice and its uncoupling activity after whole body irradiation (1,000 r). 1. Oxidative phosphorylation of Ehrllch ascites tumor cells was loosely uncoupled with the addition of ascitic lipid fraction extracted from tumor bearing mice. 2. The uncoupling activity of the lipid fraction on the oxidative phosphorylation of the tumor cells increased after whole body irradiation. 3. Ascitic lipid fraction, especially acetone soluble fraction accelerated mitochondrial swelling, and the swelling action was increased remarkably by the whole body irradiation. 4. No significant changes were observed in the proportion of acetone soluble fraction to acetone insoluble fraction in the ascitic lipid after X-irradiation, and the proportion of the both fractions was approximately 9 : 1, respectively. 5, Main compositions of total and non-esterified fatty acids in the ascitic fluid obtained from the control and X-irradiated groups were palmitic, stearic, oleic, linoleic and palmitoleic acids, and the proportions of unsaturated acids, especially oleic and linoleic acids in both fatty acid fractions were greater in the X-irradiated group. 6. Remarkable increment of unsaturated fatty acid especially linoleic acid, was also observed in the total fatty acids of the tumor cells separated from the X-irradiated group. 7. It can be concluded that an uncoupling agent extracted from ascitic fluid of the X-irradiated group was a mixture of long-chain fatty acids, especially oleic and linoleic acids. 8. It was also discussed that uncoupling oxidative phosphorylation in liver mitochondria after whole body irradiation may be caused by a similar mechanism to that in the turnor cells.

en-copyright= kn-copyright= en-aut-name=InabaKozo en-aut-sei=Inaba en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=5 article-no= start-page=247 end-page=259 dt-received= dt-revised= dt-accepted= dt-pub-year=1964 dt-pub=196410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of sodium oleate on the metabolism and size of rat liver mitochondria I. Uncoupling, shrinkage and their re?versal action by bovine serum albumin en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Effects of sodium oleate and bovine serum albumin (BSA) on rat liver mitochondrial function and structure were studied by measuring oxygen uptake, 90° light-scattering, adenosine triphosphatase activity and pyridine nucleotides fluorescence. 1. The low concentration of oleate induced the uncoupling of oxidative phosphorylation and the scattering change of mitochondria. This action of oleate differed from that of oleate at a high concentration which induces the high amplitude swelling with respect to its physiological and biochemical properties. The degrees of reversal swelling (shrinkage) and of oxygen uptake induced by oleate in the presence of Pi and succinate were altered proportionately to the concentration of oleate, and the concentration of oleate to the shrinkage coincided with that of the maximal respiratory release. 2. Antimycin A or 2, 4- dinitrophenol prevented the oleate-induced mitochondrial shrinkage, but the treatment of these agents after prior incubation with Pi and succinate allowed the shrinkage, though the degree was small in its extent compared with that in the absence of inhibitors. On the other hand, oligomycin did not affect the shrinkage with oleate. 3. BSA protected the mitochondrial phosphorylation from the uncoupling action of oleate without showing any effect of its own. A complete reversal could readily be demonstrated by a sufficient amount of BSA from the uncoupling, structural changes, and oxidation of intramitochondrial pyridine nucleotides induced by oleate in a low concentration. 4. The oleate-stimulated latent ATPase activity was proportional to the oleate-induced shrinkage of mitochondria with respect to the concentration of oleate. The latent ATPase was abolished also by the addition of a sufficient amount of BSA. 5. The action of oleate on the phosphorylation sequence of mitochondria was discussed on the basis of the present findings.

en-copyright= kn-copyright= en-aut-name=YamamotoGoki en-aut-sei=Yamamoto en-aut-mei=Goki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=6 article-no= start-page=339 end-page=350 dt-received= dt-revised= dt-accepted= dt-pub-year=1964 dt-pub=196412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=On the relation between the fatty acid composition and the swelling rate in rat liver mitochondria en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. For the purpose to clarify the relationship between the structural change and lipid composition of isolated rat liver mitochondria, lipid composition and swelling rate of mitochondria obtained from the rat of 3'-Me-DAB feeding and raised in cold room are measured, and the following results were obtained. 2. The mitochondria obtained from the liver of 3'-Me-DAB-fed rat and of rat raised in cold room show a low rate of swelling by addition of Na-oleate accompanied by the decrease in highly unsaturated fatty acids (C18:3 and C20:3or 4) and with the increase in saturated fatty acids (C16 and C18). 3. Activation energy for the mitochondrial swelling is about 16.2 Kcal in the mitochondria obtained from normal rat liver, but requires 19.7 Kcal in the mitochondria that show a low rate of swelling. The fatty acid composition, especially in glycerophosphatides which occupy about 80 per cent of total lipids, is a structural component of mitochondrial membrane, undergoes the change from former to latter in the following fashion: C16:0 21.73→32.10, C16:1 3.37→2.96, C18:0 25.0→29.75, C18:1 13.75→17.40, C18:2 23.90→16.0 and C20:3 or 4 12.23→1.79. 4. At the time of low rate swelling of mitochondria isolated from 3'-MeDAB- fed rat liver, there could be observed a marked increase of the acetone soluble lipid (simple lipids) in the total liver lipids and in the fatty acid distribution of the acetone-soluble lipids, oleic acid was markedly increased (0.838→3.81%/dry liver), despite the fact that in the acetone-insoluble fractions or in the mitochondria there are no marked changes in the oleic acid contents (1.84→2.56% or 0.212→0.246%/dry liver).

en-copyright= kn-copyright= en-aut-name=OharaSachiko en-aut-sei=Ohara en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=18 cd-vols= no-issue=4 article-no= start-page=189 end-page=205 dt-received= dt-revised= dt-accepted= dt-pub-year=1964 dt-pub=196408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial swelling induced by Ca2+ and inorganic phosphate and its related phenomena en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Some investigations have been done on the relationships between the swelling-shrinkage change, oxygen consumption and state of oxidation-reduction of pyridine nucleotides of mitochondria, and between the swelling-shrinkage change of mitochondrial structure by Ca2+ and accumlation of Ca45 in rat liver mitochondria. A parallel relationship is observed between the Ca2+ induced swelling and Ca2+ accumulation. Both of them require Pi but not Mg2+, ATP and exogenous respiratory substrates and are inhibited by respiratory inhihitors or uncouplers of oxidative phosphorylation but not by the inhibitors of phosphorylating respiration. In this case the Ca2+ is transported with the phosphate even in ice cold. Even in the presence of antimycin A, moreover, Pi-dependent Ca2+ accumulation and Ca2+ induced swelling can be overcome by addition of ATP, which are inhibited by oligomycin. In the presence of Pi, mitochondria show shrinkage by addition of Ca2+ before the high amplitude swelling, which is closely correlated to the electron ransport chain and phosphorylation process of mitochondria, and the pattern of the mitochondrial shrinkage is quite similar to that observed in the case of respiratory control by ADP in intact mitochondria. This shrinkage of mitochondria is inhibited by respiratory inhibitor or uncoupler of oxidative phosphorylation but not by the inhibitor of phosphorylating respiration. From these data, therefore, it is considerd that the Ca2+ accumulation and Ca2+ induced shrinkage-swelling of mitochondria require the energy of oxidative phosphorylation with respect to the initial step before the oligomycin block.

en-copyright= kn-copyright= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=6 article-no= start-page=317 end-page=331 dt-received= dt-revised= dt-accepted= dt-pub-year=1962 dt-pub=196212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mitochondrial Swelling and Uncoupling Activity of Long-Chain Fatty Acids en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The effect of various fatty acids on the swelling-contraction and oxidative phosphorylation of mitochondria from rat liver and Ehrlich ascites tumor cell have been studied and the results are as follows: 1. The swelling of rat liver mitochondria is induced by fatty acid. The extent of this uncoupling action is in the descending order of myristate, laurate, parlmitate, stearate and behenate in saturated fatty acid and linoleate, linoleneate, richinoleate and oleate in the unsaturated fatty acid. This swelling action is stronger with unsaturated fatty acids than that of saturated ones and cis form is stronger than trans form. 2. The uncoupling oxidative phosphorylation of rat liver mitochondria is also observed with these fatty acids and the activities are proportional to the degree of the swelling action. 3. The degree of swelling of rat liver mitochondria is proportional to the concentration of oleate and is inhibited by anaerobiosis and respiratory inhibitor except amytal. 4. The mitochondria swollen by fatty acid can be recontracted reversibly by ATP, Mg++ and bovine serum albumin. 5. The swelling action of sodium oleate is the strongest on mitochondria from rat liver, followed by those from the liver of Ehrlich ascites tumor bearing mouse, Ehrlich ascites tumor cells and solid Ehrlich tumor cells. 6. Sodium oleate inhibits the incorporation of 32p into ATP, ADP, GTP and UDPG in mitochondria.

en-copyright= kn-copyright= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OharaSachiko en-aut-sei=Ohara en-aut-mei=Sachiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoGoki en-aut-sei=Yamamoto en-aut-mei=Goki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InabaKozo en-aut-sei=Inaba en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UrakamiHiroyuki en-aut-sei=Urakami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoMichio en-aut-sei=Yamamoto en-aut-mei=Michio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=4 article-no= start-page=205 end-page=224 dt-received= dt-revised= dt-accepted= dt-pub-year=1962 dt-pub=196208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Biological effect of high and low oxygen tension--a morphological study en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. Morphological observations were carried out on the strain HeLa cells cultured under various oxygen tension. 2. The growth of the strain HeLa cells in the present experiments was markedly inhibited when they were cultured under high oxygen tension or in nitrogen gas environment. It has been clarified that air offers the most optimal gas environment. 3. Effects of the changed gas environment on the fine structures of HeLa cells were studied by phase contrast microscope and electronmicroscope. As the results it has been found that in these cells cultured under a high oxygen tension there occurs a marked swelling of mitochondria. Under anaerobic condition, however, these cells undergo degeneration, as in oxygen environment revealing no swelling of mitochondria but rather contraction. 4. Endoplasmic reticulum (ER) of HeLa cells cultured under oxygen environment is transformed from its vesicular form to lamellar form. The mechanism of lamellar transformation of ER is obscure but no morphologic connection with nuclear, cytoplasmic and mitochondrial membranes has been detected. 5. A discussion was made on these findings concerning the changes in fine structures of the cells, with a special reference to the swelling of mitochondria and morphological changes of ER under oxygen environment.

en-copyright= kn-copyright= en-aut-name=MatsuokaIwao en-aut-sei=Matsuoka en-aut-mei=Iwao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=1 article-no= start-page=9 end-page=14 dt-received= dt-revised= dt-accepted= dt-pub-year=2000 dt-pub=200002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of thyroxine on L-cysteine desulfuration in mouse liver. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The effect of exogenous thyroxine (T4) administration on the activity of rhodanese, cystathionase, and 3-mercaptopyruvate sulfurtransferase (MPST) in the mitochondrial and cytosolic fractions of mouse liver was investigated. Three groups of mice were treated for 6 consecutive days with subcutaneous injections of T4 (50 micrograms, 100 micrograms, and 250 micrograms per 100 g of body wt, respectively). The other 3 groups were given 100 micrograms of T4 per 100 g of body wt for 1, 2, or 3 days. The dose of 100 micrograms T4 per 100 g of body wt given for 6 days exerted the strongest effect on the activity of all of the investigated enzymes. In comparison to the control, rhodanese activity diminished in the mitochondrial fraction by 40% (P < 0.05), cystathionase activity diminished in the cytosolic fraction by 15% (P < 0.05), and MPST activity in the mitochondrial fraction was reduced by 34% (P < 0.05), whereas cytosolic MPST activity was unaltered. Simultaneously, in the liver homogenate, elevated levels of ATP and sulfate were observed after 6 days of T4 administration. Thus, the present results seem to suggest that in the mouse liver, after 6 days of administration of 100 micrograms T4 per 100 g of body wt, the desulfuration metabolism of L-cysteine is diminished, which is probably accompanied by an increase in oxidative L-cysteine metabolism. The dose of 100 micrograms per 100 g of body wt administered for a shorter period, and the use of a lower dosage (50 micrograms T4 per 100 g of body wt) for 6 days had a stimulatory effect upon MPST activity level, and an increased level of sulfane sulfur was observed.

en-copyright= kn-copyright= en-aut-name=WrobelMaria en-aut-sei=Wrobel en-aut-mei=Maria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UbukaToshihiko en-aut-sei=Ubuka en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YaoWen-Bin en-aut-sei=Yao en-aut-mei=Wen-Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeTadashi en-aut-sei=Abe en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Jagiellonian University affil-num=2 en-affil= kn-affil=Kawasaki University of Medical Welfare affil-num=3 en-affil= kn-affil=Beijing Tong-Ren Hospital affil-num=4 en-affil= kn-affil=Okayama University en-keyword=thyroxine kn-keyword=thyroxine en-keyword=rhodanese kn-keyword=rhodanese en-keyword=3-mercaptopyruvate kn-keyword=3-mercaptopyruvate en-keyword=sulfurtransferase kn-keyword=sulfurtransferase en-keyword=cystathionase kn-keyword=cystathionase en-keyword=sulfane sulful kn-keyword=sulfane sulful END start-ver=1.4 cd-journal=joma no-vol=54 cd-vols= no-issue=2 article-no= start-page=57 end-page=65 dt-received= dt-revised= dt-accepted= dt-pub-year=2000 dt-pub=200004 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Purification, identification and phosphorylation of annexin I from rat liver mitochondria. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Annexin was purified from rat liver mitochondria to an apparent homogeneity with a molecular weight of 35 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified mitochondrial annexin (AXmito) was identified as annexin I by an immunoblot analysis using anti-annexin I antibody. The inhibitory effect of AXmito I on porcine pancreatic phospholipase A2 activity was as potent as that of bovine lung annexin I. The presence of annexin I in mitochondria was confirmed by an electron-microscopic study. AXmito I was shown to be phosphorylated by intrinsic protein tyrosine kinases on its tyrosine residues. This annexin was also phosphorylated by protein kinase C.

en-copyright= kn-copyright= en-aut-name=YoshiiKenji en-aut-sei=Yoshii en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugimotoKatsuyoshi en-aut-sei=Sugimoto en-aut-mei=Katsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TaiYuji en-aut-sei=Tai en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KonishiRyoji en-aut-sei=Konishi en-aut-mei=Ryoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TokudaMasaaki en-aut-sei=Tokuda en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Kagawa Medical University affil-num=2 en-affil= kn-affil=Kagawa Medical University affil-num=3 en-affil= kn-affil=Kagawa Medical University affil-num=4 en-affil= kn-affil=Kagawa Medical University affil-num=5 en-affil= kn-affil=Kagawa Medical University en-keyword=annexin kn-keyword=annexin en-keyword=mitochondria kn-keyword=mitochondria en-keyword=protein tyrosine kinases kn-keyword=protein tyrosine kinases en-keyword=protein kinase C kn-keyword=protein kinase C en-keyword=Phospholipase A2 kn-keyword=Phospholipase A2 END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=5 article-no= start-page=221 end-page=233 dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=200410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Quinone formation as dopaminergic neuron-specific oxidative stress in the pathogenesis of sporadic Parkinson's disease and neurotoxin-induced parkinsonism. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia nigra. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of familial PD. Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system all play important roles in the pathogenesis and progress of PD. However, these hypotheses do not yet fully explain the mechanisms of dopaminergic neuron-specific cell loss in PD. Recently, the neurotoxicity of dopamine quinone formation by auto-oxidation of dopamine has been shown to cause specific cell death of dopaminergic neurons in the pathogenesis of sporadic PD and dopaminergic neurotoxin-induced parkinsonism. Furthermore, this quinone formation is closely linked to other representative hypotheses in the pathogenesis of PD. In this article, we mainly review recent studies on the neurotoxicity of quinone formation as a dopaminergic neuron-specific oxidative stress and its role in the etiology of PD, in addition to several neuroprotective approaches against dopamine quinone-induced toxicity.

en-copyright= kn-copyright= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Diaz-CorralesFrancisco J en-aut-sei=Diaz-Corrales en-aut-mei=Francisco J kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgawaNorio en-aut-sei=Ogawa en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University en-keyword=dopamine quinone kn-keyword=dopamine quinone en-keyword=quinoprotein kn-keyword=quinoprotein en-keyword=Parkinson’sdisease kn-keyword=Parkinson’sdisease en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=neurotoxin kn-keyword=neurotoxin END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=5 article-no= start-page=287 end-page=304 dt-received= dt-revised= dt-accepted= dt-pub-year=1979 dt-pub=197910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The mechanism of the release of hepatic enzymes in various liver diseases. 1. Alterations in cytoplasmic and mitochondrial enzyme activities in serum. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Serum glutamic oxaloacetic transaminase (GOT), mitochondrial GOT (GOTm), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase activities were determined in 43 healthy controls and in 280 cases of liver diseases. A simplified column chromatographic method coupled with UV assay was employed for separation of GOTm. The activity was measured by following decrease in abosrbance of NADH at 340 nm. The lowest activity of GOTm determined with a coefficient of variation below 10% was 6 mIU/ml. High GOTm activities were found in acute hepatitis (acute stage), subacute hepatitis and primary biliary cirrhosis and were generally associated with high total GOT (GOTt) activities. The activity ratio of GOTm/GOTt varied depending on the stage and severity of liver diseases. The GOTm/GOTt ratio was decreased in acute, fulminant and subacute hepatitides. No significant reduction in the ratio was found in bile duct obstruction, alcoholic liver injury or metastatic liver cancer. Although relatively high GOTm/GOTt ratios were found in some patients with severe hepatic injury, they had no definite association with poor prognosis. These results indicate that the marked elevation in GOTt over GPT in advanced chronic hepatitis, liver cirrhosis and primary hepatoma was mainly due to preferential leakage of cytoplasmic GOT (GOTs).

en-copyright= kn-copyright= en-aut-name=MiyakeShu en-aut-sei=Miyake en-aut-mei=Shu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University en-keyword=glutamic-oxaloacetic transaminanse kn-keyword=glutamic-oxaloacetic transaminanse en-keyword=glutamic-pyruvic transaminase ratio kn-keyword=glutamic-pyruvic transaminase ratio en-keyword=glutamic-oxaloacetic transaminase isoenzyme kn-keyword=glutamic-oxaloacetic transaminase isoenzyme en-keyword=enzyne leakage kn-keyword=enzyne leakage en-keyword=liver enzyme kn-keyword=liver enzyme en-keyword=enzyme dedifferentiation kn-keyword=enzyme dedifferentiation en-keyword=liver diseases kn-keyword=liver diseases END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=2 article-no= start-page=103 end-page=111 dt-received= dt-revised= dt-accepted= dt-pub-year=1979 dt-pub=197904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Partial purification and properties of bovine heart catalase. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Catalase was partially purified (about 380-fold purification) from the post-mitochondrial supernatant of bovine heart and compared with catalases from bovine erythrocytes and bovine liver. The electrophoretic mobility in polyacrylamide gel (pH 8.0) of heart catalase was the same as that of erythrocyte catalase and was smaller than that of the liver enzyme. The heart catalase was indistinguishable from erythrocyte catalase in regard to the molecular weights of subunit polypeptides, the inhibition patterns produced by several catalase inhibitors, and specific activity. The pH-activity curve of heart catalase consisted of a characteristic biphasic pattern with a peak at pH 7.5 and a shoulder at pH 10.

en-copyright= kn-copyright= en-aut-name=TsutsuiKen en-aut-sei=Tsutsui en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HataseOsamu en-aut-sei=Hatase en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University en-keyword=catalse kn-keyword=catalse en-keyword=muscle kn-keyword=muscle en-keyword=bovine heart kn-keyword=bovine heart END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=287 end-page=304 dt-received= dt-revised= dt-accepted= dt-pub-year=1979 dt-pub=197908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The mechanism of the release of hepatic enzymes in various liver diseases. 1. Alterations in cytoplasmic and mitochondrial enzyme activities in serum. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Serum glutamic oxaloacetic transaminase (GOT), mitochondrial GOT (GOTm), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase activities were determined in 43 healthy controls and in 280 cases of liver diseases. A simplified column chromatographic method coupled with UV assay was employed for separation of GOTm. The activity was measured by following decrease in abosrbance of NADH at 340 nm. The lowest activity of GOTm determined with a coefficient of variation below 10% was 6 mIU/ml. High GOTm activities were found in acute hepatitis (acute stage), subacute hepatitis and primary biliary cirrhosis and were generally associated with high total GOT (GOTt) activities. The activity ratio of GOTm/GOTt varied depending on the stage and severity of liver diseases. The GOTm/GOTt ratio was decreased in acute, fulminant and subacute hepatitides. No significant reduction in the ratio was found in bile duct obstruction, alcoholic liver injury or metastatic liver cancer. Although relatively high GOTm/GOTt ratios were found in some patients with severe hepatic injury, they had no definite association with poor prognosis. These results indicate that the marked elevation in GOTt over GPT in advanced chronic hepatitis, liver cirrhosis and primary hepatoma was mainly due to preferential leakage of cytoplasmic GOT (GOTs).

en-copyright= kn-copyright= en-aut-name=MiyakeShu en-aut-sei=Miyake en-aut-mei=Shu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University en-keyword=glutamic-oxaloacetic transaminase kn-keyword=glutamic-oxaloacetic transaminase en-keyword=mitochondrial glutamic-oxaloacetic transaminanse kn-keyword=mitochondrial glutamic-oxaloacetic transaminanse en-keyword=glutamic-pyruvic transaminase kn-keyword=glutamic-pyruvic transaminase en-keyword=liver diseases kn-keyword=liver diseases END start-ver=1.4 cd-journal=joma no-vol=59 cd-vols= no-issue=2 article-no= start-page=37 end-page=44 dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=200504 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of trapidil after crush injury in peripheral nerve. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

In this study, we evaluated the effects of trapidil on crush injury by monitoring nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels and by transmission electron microscopy in the rat sciatic nerve. The sciatic nerve was compressed for 20 sec by using a jewelers forceps. Trapidil treatment groups were administrated a single dose of trapidil (8 mg/kg) intraperitoneally just after the injury. The crush and crush + trapidil treatment groups were evaluated on the 2nd, 7th, 15th, 30th and 45th days of the post-crush period. On the 7th and 15th days, damage in thin and thick myelinated axons, endoneural edema and mitochondrial swelling were less severe in the trapidil group histopathologically. These findings supported the idea that trapidil prevented cell damage and edema at the injury site. Day/group interaction with regard to serum nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels did not show significant changes.

en-copyright= kn-copyright= en-aut-name=KurtogluZeliha en-aut-sei=Kurtoglu en-aut-mei=Zeliha kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OzturkAhmet Hakan en-aut-sei=Ozturk en-aut-mei=Ahmet Hakan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BagdatogluCelal en-aut-sei=Bagdatoglu en-aut-mei=Celal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=PolatGurbuz en-aut-sei=Polat en-aut-mei=Gurbuz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AktekinMustafa en-aut-sei=Aktekin en-aut-mei=Mustafa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UzmanselDeniz en-aut-sei=Uzmansel en-aut-mei=Deniz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=CamdevirenHandan en-aut-sei=Camdeviren en-aut-mei=Handan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=BagdatogluOzlen en-aut-sei=Bagdatoglu en-aut-mei=Ozlen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SargonMustafa en-aut-sei=Sargon en-aut-mei=Mustafa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Mersin University affil-num=2 en-affil= kn-affil=Mersin University affil-num=3 en-affil= kn-affil=Mersin University affil-num=4 en-affil= kn-affil=Mersin University affil-num=5 en-affil= kn-affil=Mersin University affil-num=6 en-affil= kn-affil=Mersin University affil-num=7 en-affil= kn-affil=Mersin University affil-num=8 en-affil= kn-affil=Mersin University affil-num=9 en-affil= kn-affil=Hacettepe University en-keyword=trapidil kn-keyword=trapidil en-keyword=crush injury kn-keyword=crush injury en-keyword=peripheral nerve kn-keyword=peripheral nerve en-keyword=electron microscopy kn-keyword=electron microscopy en-keyword=nitric oxide kn-keyword=nitric oxide END start-ver=1.4 cd-journal=joma no-vol=59 cd-vols= no-issue=6 article-no= start-page=253 end-page=260 dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=200512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The augmentation of TNFalpha-induced cell death in murine L929 fibrosarcoma by the pan-caspase inhibitor Z-VAD-fmk through pre-mitochondrial and MAPK-dependent pathways. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

We investigated the mechanism of the pan-caspase inhibitor z-VAD-fmk's augmentation of TNFalpha-induced L929 cell death and found this mechanism differs from that of TNFalpha-induced L929 cell death. In the presence of 20 ng/ml TNFalpha, z-VAD-fmk initiated apoptosis and necrosis in the majority of L929 cells as measured by an agarose gel electrophoresis and lactate dehydrogenase(LDH)activity based assay. Mitochondrial permeability transition (MPT) inhibitor (cyclosporine A) effectively inhibited z-VAD-fmk-augmented cell death. In addition, z-VAD-fmk plus TNFalpha increased Bax expression without affecting Bcl-2 and cytochrome expression. Western-blot analysis showed that z-VAD-fmk plus TNFalpha caused persistent JNK activation and ERK inactivation. Poly(ADP-ribose) polymerase (PARP) inhibitor (DPQ) effectively reversed the cell death which was augmented by z-VAD-fmk, and z-VAD-fmk plus TNFalpha also caused PARP cleavage to an 85 KDa fragment. These results indicate that in the presence of TNFalpha, z-VAD-fmk further augments cell death which requires the mitochondrial permeability transition and the JNK activation. However, we did not detect the changes in cytochrome c expression and the participation of caspase-9 in this process, suggesting that there might exist an unknown signal pathway(s) from the mitochondria to the downstream protein PARP, which is cleaved in a caspase-independent manner.

en-copyright= kn-copyright= en-aut-name=HuangJian en-aut-sei=Huang en-aut-mei=Jian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WuLijun en-aut-sei=Wu en-aut-mei=Lijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TashiroShin-ichi en-aut-sei=Tashiro en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OnoderaSatoshi en-aut-sei=Onodera en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkejimaTakashi en-aut-sei=Ikejima en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Shenyang Pharmaceutical University affil-num=2 en-affil= kn-affil=Shenyang Pharmaceutical University affil-num=3 en-affil= kn-affil=Showa Pharmaceutical University affil-num=4 en-affil= kn-affil=Showa Pharmaceutical University affil-num=5 en-affil= kn-affil=Shenyang Pharmaceutical University en-keyword=TNF? kn-keyword=TNF? en-keyword=caspase kn-keyword=caspase en-keyword=Bax/Bcl-2 kn-keyword=Bax/Bcl-2 en-keyword=MAPK kn-keyword=MAPK en-keyword=PARP kn-keyword=PARP END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=1 article-no= start-page=1 end-page=10 dt-received= dt-revised= dt-accepted= dt-pub-year=1985 dt-pub=198502 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Branched chain amino acid transaminase and branched chain alpha-ketoacid dehydrogenase activity in the brain, liver and skele?tal muscle of acute hepatic failure rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Branched chain amino acid (BCAA) transaminase activity increased in both the mitochondrial and supernatant fractions of brain from hepatic failure rats, in which a partial hepatectomy was performed 24h following carbon tetrachloride (CCl4) administration, although the activity of liver and skeletal muscle was the same as in control rats. The elevation of mitochondrial BCAA transaminase activity in liver-injured rats was partly due to increased activity of brain specific Type III isozyme. Branched chain alpha-ketoacid (BCKA) dehydrogenase in the brain homogenates was not significantly altered in acute hepatic failure rats, while the liver enzyme activity was markedly diminished. BCKA dehydrogenase activity in the brain homogenates was inhibited by adding ATP to the assay system, and was activated in vitro by preincubating the brain homogenate at 37 degrees C for 15 min. These findings suggest that brain BCAA catabolism is accelerated in acute hepatic failure rats.

en-copyright= kn-copyright= en-aut-name=TakeiNobuyuki en-aut-sei=Takei en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University en-keyword=branched chain amino acids kn-keyword=branched chain amino acids en-keyword=branched chain amino acid transaminase kn-keyword=branched chain amino acid transaminase en-keyword=branched chain alpha-ketoacied dehydrogenase kn-keyword=branched chain alpha-ketoacied dehydrogenase en-keyword=acute hepatic failure kn-keyword=acute hepatic failure en-keyword=brain kn-keyword=brain END start-ver=1.4 cd-journal=joma no-vol=39 cd-vols= no-issue=4 article-no= start-page=289 end-page=295 dt-received= dt-revised= dt-accepted= dt-pub-year=1985 dt-pub=198508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of tricyclic drugs on mitochondrial membrane. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The effects of tricyclic drugs (clomipramine, imipramine, chlorpromazine and promethazine) on isolated liver mitochondria of rats were examined. All the drugs tested accelerated state 4 respiration. Their stimulative potency at concentrations below 100 microM was in the order of chlorpromazine greater than clomipramine greater than imipramine, promethazine. On state 3 respiration, the chlorine containing drugs had an inhibitive effect at high concentrations, while the other drugs seemed to have a slightly stimulative effect. These drugs stimulated latent ATPase activity of mitochondria. Clomipramine and chlorpromazine inhibited 2, 4-dinitrophenol-stimulated ATPase activity in a dose-dependent fashion. Imipramine also inhibited 2, 4-dinitrophenol-stimulated ATPase activity at high concentrations. Promethazine, however, had almost no effect. All the drugs induced potassium release from mitochondrial vesicles, and their potency was in the order of clomipramine greater than chlorpromazine greater than imipramine greater than promethazine. These results suggest that clomipramine, imipramine, chlorpromazine and promethazine cause impediments in both mitochondrial respiration and ion compartmentation, and that the chlorine containing drugs are more toxic than others on the functions of the mitochondrial membrane.

en-copyright= kn-copyright= en-aut-name=EtoKohei en-aut-sei=Eto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukudaTamotsu en-aut-sei=Fukuda en-aut-mei=Tamotsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ArakiYasunori en-aut-sei=Araki en-aut-mei=Yasunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueBunji en-aut-sei=Inoue en-aut-mei=Bunji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OgataMasana en-aut-sei=Ogata en-aut-mei=Masana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University en-keyword=tricyclic drugs kn-keyword=tricyclic drugs en-keyword=mitochondria kn-keyword=mitochondria en-keyword=oxidative phosphorylation kn-keyword=oxidative phosphorylation en-keyword=potassium release kn-keyword=potassium release en-keyword=ATPase activity kn-keyword=ATPase activity END start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=3 article-no= start-page=147 end-page=152 dt-received= dt-revised= dt-accepted= dt-pub-year=1976 dt-pub=197606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The presence of phosphate-binding protein in inner mitochondrial membrane en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Phosphate-binding protein(s) was found in the inner mitochondrial membrane of calf heart by Sephadex G-200 and G-25 gel filtration. The binding activity was inhibited by N-ethylmaleimide and competed by a large amount of cold phosphate. The amount of phosphate bound to the fraction was 29 nmoles per mg of protein. Affinity chromatography with phosphate-bound Sepharose 4B confirmed the presence of phosphate-binding protein(s) in the active fraction of mitochondrial membrane fractionated by gel filtration.

en-copyright= kn-copyright= en-aut-name=HataseOsamu en-aut-sei=Hatase en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsutsuiKen en-aut-sei=Tsutsui en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=1 article-no= start-page=1 end-page=8 dt-received= dt-revised= dt-accepted= dt-pub-year=1961 dt-pub=196102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Studies on the organellae of liver of cancer bearing animals I. Distribution of mucopolysacoharides in the organellae of liver in cancer (Hepatoma AH 130) bearing animals en-subtitle= kn-subtitle= en-abstract= kn-abstract=

For the purpose to reveal whether or not the liver and the cell organellae are responsible for the abnormal metabolism of polysaccharides found in cancer bearing individuals, the author analyzed the liver and ascites with tumor cells of AH 130 hepatoma bearing rats biochemically with some histochemical observations. A quantitative increase in polysaccharides accompanied by the production of unusual polysaccharides is found in the supernatant of liver from cancer bearing rats, but not from mitochondrial or microsomal fractions. Tumor cells themselves and ascites fluid do not contain the abnormal polysaccharides found in the liver supernatant.

en-copyright= kn-copyright= en-aut-name=KimotoTetsuo en-aut-sei=Kimoto en-aut-mei=Tetsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=4 article-no= start-page=205 end-page=209 dt-received= dt-revised= dt-accepted= dt-pub-year=1998 dt-pub=199808 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ultrastructural and Biochemical Changes of the Brain after Peripheral Administration of Phorbol Myristate Acetate en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The ultrastructural and biochemical changes in the brain tissue of 20 mice were studied. The mice, separated into acute and chronic groups, were injected with phorbol myristate acetate (PMA) to trigger the release of free radicals. Malondialdehyde measurement and electron microscopic examination were applied for the evaluation of the effects of the free radicals. The level of lipid peroxide in the chronic PMA group was found to be significantly higher than it was in the acute PMA group (P < 0.005). An electron microscopic examination of the acute group revealed disruption of the mitochondrial cristae and dilatation of the endoplasmic reticulum in the neurons. Myelin sheaths of the nerve fibers exhibited focal structural changes. Neurons and neuroglial cells in the chronic group, however, exhibited distinct ultrastructural alterations. The ultrastructural and biochemical findings showed that free radicals lead to brain damage.

en-copyright= kn-copyright= en-aut-name=BozkirMemducha Gulhal en-aut-sei=Bozkir en-aut-mei=Memducha Gulhal kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DereFahri en-aut-sei=Dere en-aut-mei=Fahri kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MeteUfuk Ozgu en-aut-sei=Mete en-aut-mei=Ufuk Ozgu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KayaMehmet en-aut-sei=Kaya en-aut-mei=Mehmet kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Cukurova University affil-num=2 en-affil= kn-affil=Cukurova University affil-num=3 en-affil= kn-affil=Cukurova University affil-num=4 en-affil= kn-affil=Cukurova University en-keyword=free radical kn-keyword=free radical en-keyword=phorbol myristate acetate kn-keyword=phorbol myristate acetate en-keyword=malodialdehyde kn-keyword=malodialdehyde en-keyword=brain kn-keyword=brain en-keyword=ultrastruture kn-keyword=ultrastruture END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=1 article-no= start-page=29 end-page=35 dt-received= dt-revised= dt-accepted= dt-pub-year=1971 dt-pub=197102 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Conformational studies of mitochondrial DNA en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Ring DNA from rat liver mitochondria has been examined by circular dichroism (CD) in the region of the 225 to 320 m/~ and the followings have been clarified. The ring DNA gives a CD spectral curve somewhat different from linear DNA from nuclei, showing a big positive peak at 266 m/~ and a small negative band at 243 m!~. That is, the positive CD band of ring DNA shifted by about 7 m/~ to the shorter wavelength side from the band of the ordinary nuclear DNA, 273 m!~. Negative band appeared at the same region as that of linear DNA but reduced in depth. Heat denaturation of the ring DNA induced a red shift of the positive band, by about 4 mp., but no change in negative band. From these experimental results it has been concluded that the ring DNA has highly twisted conformation and high in G.C contents, both of which are responsible for the blue shift of the CD spectrum.

en-copyright= kn-copyright= en-aut-name=ItoNobutaka en-aut-sei=Ito en-aut-mei=Nobutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyaharaMasanobu en-aut-sei=Miyahara en-aut-mei=Masanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SenoSatimaru en-aut-sei=Seno en-aut-mei=Satimaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=3 article-no= start-page=179 end-page=187 dt-received= dt-revised= dt-accepted= dt-pub-year=1971 dt-pub=197106 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relation between ANS fluorescence and energy states of mitochondria en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1. ANS fluorescence change at various energized stages of mitochondria was investigated. 2. Freshly prepared mitochondria manifest ANS fluorescence change during anaerobic-aerobic transition, but aged and inner mitochondrial membrane show remarkable changes. 3. These data suggest that freshly prepared mitochondria or those in energized state exhibit less hydrophobic environments or decrease the binding site of ANS. 4. Energy dependent light scattering changes indicating the configurational changes of mitochondria cannot be said to be identical with the pattern of ANS fluorescence changes indicating the conformational change of mitochondrial membrane. 5. Polarity of the membrane structure and binding site of ANS in submitochondrial particles and mitochondrial membranes have been discussed.

en-copyright= kn-copyright= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=5 article-no= start-page=493 end-page=504 dt-received= dt-revised= dt-accepted= dt-pub-year=1971 dt-pub=197110 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Change of proton gradient in mitochondria at various energy states en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Changes of H+ gradient at various energy states of mitochondria were studied. There was a close relation between the extent of H+ gradient and the level of ATP formation; the former decreased as a result of ATP synthesis but was not completely abolished. A partial depression of H+ gradient was also observed in the presence of uncouplers of oxidative phosphorylation. The H+ gradient seemed to be more closely related to the ion translocation than ATP formation. In the presence of Ca++ the energy of H+ gradient was utilized in translocating Ca++ rather than synthesizing ATP. These findings further substantiate the chemiosmotic theory of MITCHELL on mitochondrial electron and energy transfer.

en-copyright= kn-copyright= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=PereiraeJ. Torres en-aut-sei=Pereirae en-aut-mei=J. Torres kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MustafaMohammad G. en-aut-sei=Mustafa en-aut-mei=Mohammad G. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=4 article-no= start-page=245 end-page=253 dt-received= dt-revised= dt-accepted= dt-pub-year=1971 dt-pub=197108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Electron microscopic observation of mitochondrial DNA isolated from a human kidney: circular dimers in histologically normal organ mitochondria en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Circular DNA isolated from human kidney mitochondria was studied by electron microscopy. I. Mean contour length of monomers of the mitochondrial DNA was 4.96 ± SE 0.28 /μ 2. The complex molecules (oligomers) of mitochondrial DNA were observed in frequency of 6.2 per cent. Among them circular dimers accounted for two per cent of all circular DNA molecules. 3. Circular DNA fibers with an intermediate perimeter between the monomer and dimer, and with a contour length shorter than 3 μ were occasionally observed. 4. Some discussions were made on the emergence of the circular dimer.

en-copyright= kn-copyright= en-aut-name=SekiShuji en-aut-sei=Seki en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HirataSeiichi en-aut-sei=Hirata en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=42 cd-vols= no-issue=1 article-no= start-page=7 end-page=14 dt-received= dt-revised= dt-accepted= dt-pub-year=1988 dt-pub=198802 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect of phenol and halogenated phenols on energy transfer reactions of rat liver mitochondria. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The in vitro effects of phenol and p-halogenated phenols on mitochondrial energy transfer reactions were examined using isolated rat liver mitochondria. The relationship between physiochemical properties of phenolic compounds and their effects on mitochondria were studied. Phenol and p-halogenated phenols induced the release of K+ ions from mitochondria, suggesting a change in permeability to K+ ions. A decrease in the respiratory control index, an increase in K+ release and stimulation of latent ATPase activity were observed with these compounds in the descending order of p-iodophenol, p-bromophenol, p-chlorophenol, p-fluorophenol and phenol. The concentrations of the phenolic compounds resulting in fifty percent inhibition of the respiratory control index and those resulting in fifty percent release of K+ ions significantly correlated with Hammett's substituent constant (sigma) and the hydrophobic binding constant (pi) of the compounds.

en-copyright= kn-copyright= en-aut-name=IzushiFumio en-aut-sei=Izushi en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriTakaaki en-aut-sei=Mori en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OgataMasana en-aut-sei=Ogata en-aut-mei=Masana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University en-keyword=phenol kn-keyword=phenol en-keyword=mitochondria kn-keyword=mitochondria en-keyword=oxidative phosphorylation kn-keyword=oxidative phosphorylation en-keyword=Hammett's substituent constant kn-keyword=Hammett's substituent constant en-keyword=hydrophobic bindung constant kn-keyword=hydrophobic bindung constant END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=3 article-no= start-page=141 end-page=150 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=200806 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dopaminergic neuron-specific oxidative stress caused by dopamine itself en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Oxidative stress, including the reactive oxygen or nitrogen species generated in the enzymatical oxidationor auto-oxidation of an excess amount of dopamine, is thought to play an important role in dopaminergic neurotoxicity. Dopamine and its metabolites containing 2 hydroxyl residues exert cytotoxicityin dopaminergic neuronal cells, primarily due to the generation of highly reactive dopamine and DOPA quinones. Dopamine and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. Furthermore, the quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases. Therefore, pathogenic effects of the dopamine quinone have recently focused on dopaminergicneuron-specific oxidative stress. In this article, we primarily review recent studies on the pathogenicity of quinone formation, in addition to several neuroprotective approaches against dopaminequinone-induced dysfunction of dopaminergic neurons.

en-copyright= kn-copyright= en-aut-name=MiyazakiIkuko en-aut-sei=Miyazaki en-aut-mei=Ikuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsanumaMasato en-aut-sei=Asanuma en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=dopamine quinone kn-keyword=dopamine quinone en-keyword=quinoprotein kn-keyword=quinoprotein en-keyword=methamphetamine kn-keyword=methamphetamine en-keyword=Parkinson?s disease kn-keyword=Parkinson?s disease en-keyword=L-DOPA kn-keyword=L-DOPA END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=5 article-no= start-page=367 end-page=375 dt-received= dt-revised= dt-accepted= dt-pub-year=1975 dt-pub=197510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phosphorylation of purine and pyrimidine nucleosides by isolated rat liver mitochondria en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Formation of 5'-AMP, 5'-GMP, 5'-CMP and 5'UMP was confirmed in isolated rat liver mitochondria incubated with alpha-ketoglutarate, inorganic phosphate, purine nucleoside and pyrimidine nucleoside. Increased incorporation of 32Pi into ATP, GTP and UTP was observed by adding purine- and pyrimidine nucleosides. The phosphorylation of nucleosides was inhibited severely by arsenite and affected slightly by the addition of nuclear or post-mitochondrial fraction.

en-copyright= kn-copyright= en-aut-name=InabaKozo en-aut-sei=Inaba en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=2 article-no= start-page=121 end-page=128 dt-received= dt-revised= dt-accepted= dt-pub-year=1977 dt-pub=197704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Search for virus specific DNA sequences and viral particles in mitochondria of avian leukemic myeloblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=

The intracellular localization of the avian myeloblastosis virus (AMV) genome was studied. Nuclear and mitochondrial DNAs from myeloblasts were examined by hybridization with 32P labeled AMV-RNA of high molecular weight for the presence of virus specific DNA sequences. Nuclear DNA (nDNA) from myeloblasts specifically hybridized with viral RNA, whereas purified closed circular mitochondrial DNA (mtDNA) did not hybridize with viral RNA. It was therefore concluded that viral genome was present in nuclear DNA and not in mitochondrial DNA. Likewise, in normal chick cells, nDNA but not mtDNA hybridized with viral RNA.

en-copyright= kn-copyright= en-aut-name=OguraHajime en-aut-sei=Ogura en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=2 article-no= start-page=141 end-page=146 dt-received= dt-revised= dt-accepted= dt-pub-year=1977 dt-pub=197704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=RNA synthesis in mitochondria isolated from rat liver en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Mitochondrial RNA (mtRNA) was synthesized from purine and pyrimidine nucleosides in coupling with oxidative phosphorylation using isolated mitochondria. The in vivo synthesized mtRNA was adenine-uracil rich and sedimented at about 20 S by sucrose density gradient centrifugation. A major part of the newly synthesized mtRNA was shown to be poly (A)-containing RNA by the resistance to the digestion with pancreatic RNase and RNase T1 and the affinity to poly (U)-Sepharose columns or Millipore filters.

en-copyright= kn-copyright= en-aut-name=InabaKozo en-aut-sei=Inaba en-aut-mei=Kozo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OdaTakuzo en-aut-sei=Oda en-aut-mei=Takuzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=51 cd-vols= no-issue=2 article-no= start-page=55 end-page=62 dt-received= dt-revised= dt-accepted= dt-pub-year=1997 dt-pub=199704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A 55-kDa endonuclease of mammalian mitochondria: comparison of its subcellular localization and endonucleolytic properties with those of endonuclease G en-subtitle= kn-subtitle= en-abstract= kn-abstract=

A novel endonuclease of 55-kDa was found in rat liver mitochondria by a zymographic assay, in addition to the 29 kDa enzyme that is well-known as endonuclease G (Endo G). Subcellular localization of these enzymes in rat liver cells was examined by biochemical fractionation. Endo G was located in both nuclei and mitochondria as has been previously reported, while the 55-kDa enzyme was only detected in the mitochondrial fraction. The levels of the endonucleases in the mitochondria varied greatly among the rat organs, and the activity in the heart was about 30 times higher than that in the liver. The 55-kDa enzyme and Endo G were extracted from bovine heart mitochondria with 0.4 M NaCl. During purification the 55-kDa enzyme and Endo G were copurified because of their similar chromatographic behavior, so they were separated by gel filtration or electrophoresis in the presence of SDS and the proteins were then renatured. The nucleolytic properties of the 55-kDa enzyme resembled those of Endo G and other known mitochondrial nucleases. The enzyme degraded single-stranded DNA more rapidly than duplex DNA at a weak alkaline pH, requiring Mg2+ or Mn2+ but not Ca2+ or Zn2+. Nicks generated by the enzyme had 5′-P and 3′-OH ends. The 55-kDa enzyme, like Endo G, displayed an unusually strong preference to nick within a (dG)n ? (dC)n tract.

en-copyright= kn-copyright= en-aut-name=IkedaShogo en-aut-sei=Ikeda en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaHaruko en-aut-sei=Hasegawa en-aut-mei=Haruko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KaminakaShinobu en-aut-sei=Kaminaka en-aut-mei=Shinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=Okayama University of Science affil-num=2 en-affil= kn-affil=Okayama University of Science affil-num=3 en-affil= kn-affil=Okayama University of Science en-keyword=activity gel analysis kn-keyword=activity gel analysis en-keyword=endonuclease kn-keyword=endonuclease en-keyword=endonuclease G kn-keyword=endonuclease G en-keyword=mitochondrial DNA kn-keyword=mitochondrial DNA en-keyword=oxidative damage kn-keyword=oxidative damage END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=4 article-no= start-page=227 end-page=230 dt-received= dt-revised= dt-accepted= dt-pub-year=1995 dt-pub=199508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Expression of Fas antigen and Bcl-2 protein in hepatocellular carcinoma. en-subtitle= kn-subtitle= en-abstract= kn-abstract=

Fas antigen (ag) is a cell surface protein known to trigger apoptosis in a variety of cells upon specific antibody binding. On the other hand, Bcl-2 protein, an oncogene product located at the mitochondrial inner surface, prolongs cell survival by blocking apoptosis. In this study we examined the expression of Fas ag and bcl-2 protein in 17 cases of hepatocellular carcinoma (HCC) to determine their role on HCC. By flow cytometric analysis, mean (SD) value of the expression of Fas ag on hepatocytes derived from normal liver, diseased liver (chronic hepatitis or liver cirrhosis) and HCC was 5.8 (4.7)%, 10.3 (6.9)%, and 24.0 (18.2)%, respectively. Fas ag expression on hepatoma cells was significantly greater than normal and diseased liver cells. The expression of Bcl-2 protein in normal liver, diseased liver and HCC was 4.3 (8.5)%, 0.8 (2.5)% and 2.1 (3.4)%, respectively, and the difference was not significant. These results suggest that induction of apoptosis may be a possible therapy against HCC.

en-copyright= kn-copyright= en-aut-name=HamazakiKeisuke en-aut-sei=Hamazaki en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=GochiAkira en-aut-sei=Gochi en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsubaraNagahide en-aut-sei=Matsubara en-aut-mei=Nagahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriMazanobu en-aut-sei=Mori en-aut-mei=Mazanobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OritaKunzo en-aut-sei=Orita en-aut-mei=Kunzo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University en-keyword=apoptosis kn-keyword=apoptosis en-keyword=Fas antigen kn-keyword=Fas antigen en-keyword=Bcl-2 kn-keyword=Bcl-2 en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=2 article-no= start-page=82 end-page=88 dt-received= dt-revised= dt-accepted= dt-pub-year=1956 dt-pub=195604 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Fate in Guinea-Pigs of Intraven-ously Injected I131-γ-Globulin en-subtitle= kn-subtitle= en-abstract= kn-abstract=

1) The fate and rate of degradation of I131 labelled rabbit γ-globulin, which retained its native antigenicity and antibody specificity was studied in the guinea-pigs. 2) Blood elimination rate of heterologous γ-globulin is higher than that of homologous γ-globulin. 3) Denatured and digested γ-globulin departs from the blood more rapidly than the native one, and urinary excretion rates of denaturated and digested γ-globulin are higher than that of the native one. It is inferred, therefore, that the denatured and digested γ-globnlin is more liable to be resolved and decomposed in the reticulo-endothelial organs than the native one. And the value obtained from the urinary excretion reflects the rate of protein break down in some cellular compartments. 4) Following the plasmaphresis the increase in antigen elimination was lessened and delayed as compared with control animals. 5) The organ distribution of heterologous I131-γ-globulin is to the lymphnode> the spleen> the liver> the lung> the kidney> the intestine in descending order. Heterologous I 131 -γ- globulin is deposited in greater quantity in the reticulo-enclotherial organ than other single organ. 6) Following the intravenous injection of I131 labelled antigens, the ratio of the specific activity of mitochondria and microsom to that of whole liver homogenate was determined over a period from 15 minutes to 3 hours in guinea-pigs, and following results were obtained. a) Organ and intracellular distribution of Il3l labelled homologous γ-globulin shows no great difference compared to that of heterologous one. b) The intracellular distribution of heterologous γ-globulin is in mitochondrial> microsomal> nuclear fraction in descending order. c) The heterologous γ-globulin quantity of mitochondrial fraction or microsomal fraction in the spleen is higher than that of the liver. 7) The antibody distribution of intracellular glanules measured in terms of radioactivity with a Geiger-Muller counter, after the reaction of I131 labelled antigen. The quantity of distribution of intracellular glanules decreases in mitochondrial fraction> microsomal fraction> nuclear fraction in descending order.

en-copyright= kn-copyright= en-aut-name=OgataMasana en-aut-sei=Ogata en-aut-mei=Masana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MochizukiYoshio en-aut-sei=Mochizuki en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=4-2 article-no= start-page=1921 end-page=1927 dt-received= dt-revised= dt-accepted= dt-pub-year=1959 dt-pub=19590405 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Cytochemical Studies on the Mitochondria of Blood Cells Part 4. Cytochemical Study on the Mitochondria of Blood Cells with the Electron Microscope kn-title=血球ミトコンドリアの細胞化学的研究 第4編 血球ミトコンドリアの細胞化学的電子顕微鏡的研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In order to elucidate the microstructures of the mitochondria in blood cells in the relation with the sites of enzyme activities the author carried out electron microscopic observations on the ultra-thin sectioned specimens prepared from the normal blood cells on which the cytochemical reaction of the respiratory enzyme system has been made with the use of potassium tellurite, a heavy metal salt. As the result, it has been verified that the terminal respiratory enzyme system is localized mainly in mitochondria, and that these are significant differences in the enzyme activity of mitochondria not only between those belonging to the different kind of blood cells but also even in those found in a cell. It has also been demonstrated that these enzymes are found as a farily dense contiguous mass mainly locating in the cristae of mitochondrion, and some in the mitochondrial membrane. These observations show that there are some differences in the enzyme activity between the membrane and the cristae of mitochondria. en-copyright= kn-copyright= en-aut-name=SakaiAkira en-aut-sei=Sakai en-aut-mei=Akira kn-aut-name=酒井晃 kn-aut-sei=酒井 kn-aut-mei=晃 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部病理学教室 END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=2-2 article-no= start-page=879 end-page=883 dt-received= dt-revised= dt-accepted= dt-pub-year=1959 dt-pub=19590228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Reticulocyte Ripening Subsuances Part 3. The cellulor Origin and the characterisbics of the Ripening Substance kn-title=網赤血球成熟物質に関する研究 第三編 網赤血球成熟物質の起原とその性格 en-subtitle= kn-subtitle= en-abstract= kn-abstract=From the results presented in Part 2 it is supposed that the reticulocyte ripening substances in the bovine liver found by the author may be protein belonging to a globulin fraction or a substance attached to some particles of the cytoplasm, which can not be precipitated by the general centrifugation. The supernatant obtained from the saline extract by centrifuging at a low speed was again put to ultra-centrigu-gation at 40,000 r. p. m., thus splitting fraction into two, soluble fractions and microsome or mitochondrial fractions. Ripening test on reticulocytes proved that the effective substance had been transfered to the soluble fraction. The globulin fraction obtained from the saline exfract by the half saturation with ammonium sulfate also proved to be effective. Electro-paper chromatography of the protein obtained from the saline extract revealed that it contained a fraction of γ-globulin which was found to be lacking in the water extract. Thus the ripening substance of reticulocyte has been prove to be a protein belonging to the γ-globulin fraction originated from the hyaloplasm. en-copyright= kn-copyright= en-aut-name=SanadaHiroshi en-aut-sei=Sanada en-aut-mei=Hiroshi kn-aut-name=真田博史 kn-aut-sei=真田 kn-aut-mei=博史 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部病理学教室 END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=2 article-no= start-page=439 end-page=445 dt-received= dt-revised= dt-accepted= dt-pub-year=1958 dt-pub=19580228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Biochemical and Histochemical Studies on ATP-ase Activities of Blood and Tissue Cells Part 3. The Effects of Anti-Leukemic Agents, Nitrogen Mustard n-Oxide (NMNO) and Colchicine, on the ATP-ase Activity kn-title=血球及び組織細胞のATP-ase活性に関する生化学的並びに組織化学的研究 第3編 白血病化学療法剤のATP-ase活性に及ぼす影響について en-subtitle= kn-subtitle= en-abstract= kn-abstract=Among the various anti-leukemic agents, nitrogen mustrad and its derivatives have the similar biological effects identical with x-ray inactivating the SH group. Following up the author's former reports, in which a marked fluctuation of ATP-ase activity in various tissues of the x-ray irradiated mice was described, the author reports the effect of NMNO on the ATP-ase activities of the liver, spleen, heart, kidney and duodenum of mice. By a single injection of 1% NMNO, 300 mg/Kg., most of the adult mice died after 6 to 8hours. Hourly observations revealed the marked fluctuation of ATP-ase activitity in various organs as in the case of x-ray irradiation. The activities both of myosin and mitochondrial ATP-ase decreased slightly in every organ 30 minutes after the injection of NMNO, and then increase slightly reaching nearly the normal level after 3 hours. Further obverations revealed that the transient recovery of activities decreased again, reaching the level of inorganic P contents proper to each organ 7 hours after injection. The histochemical observation revealed also a marked decrease in the activity of ATP-ase. The inhibitory effect of NMNO to the ATP-ase activities was also proved in vitro, adding 10(-2)mol. NMNO in the incubating media. The colchine, a mitotic poison, added in the same media 10(-2)mol. effected only a slight decrease in ATP-ase activity. The incubation with L-cysteine after the treatment wiht NMNO restored the ATP-ase activity to a certain degrree. In the case treated with NMNO a marked decrease in the reactions of liver parenchymal cells, biliary tubules, blood cells of splenic pulp, cardiac fibers, the basillar part of epithelial cells of renal tubules is observable; and reactions of peripheral blood and blood in bone marrow, which received no effect from X-ray irradiation, are reduced markedly. However, when the reaction is made to take place in the substrate loaded with cysteine, only the reactions of cardiac fibers and liver parenchymal cells are restored to a certain degree. en-copyright= kn-copyright= en-aut-name=OhtaniKyohichiro en-aut-sei=Ohtani en-aut-mei=Kyohichiro kn-aut-name=大谷恭一郎 kn-aut-sei=大谷 kn-aut-mei=恭一郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部病理学教室 END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=2 article-no= start-page=431 end-page=437 dt-received= dt-revised= dt-accepted= dt-pub-year=1958 dt-pub=19580228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Biochmical and Histochemical Studies on ATP-ase Activities of Blood and Tissue Cells Part 2. Observations on the Animals irradiated with X-Ray kn-title=血球及び組織細胞のATP-ase活性に関する生化学的並びに組織化学的研究第2編 X線照射動物に於けるATP-ase活性について en-subtitle= kn-subtitle= en-abstract= kn-abstract=Generally it is accepted that X-ray irratiation in vivo, attacking H(2)O molecules, produces OH, O(2)H, H(2)O(2) etc., and the oxydation invoked by these by-products inhibits the enzymatic activity of the SH group and others. Bearing this point in mind, changes of ATP-ase activities in the liver, spleen, heart, kidney, and peripheral blood as well as bone marrow have been examined along with the lapse of time in the rabbits irradiated with a quite substantial amount of X-ray irradiation, namely, 2,000γ each. Chemical estimation proved that myosin ATP-ase activities of cardiac muscle and bone marrow are increased immeadiately after irradiation while the activities of all other excepting these two are considerably reduced. The ATP-ase activities of the liver, spleen, kidney, and Peripheral blood increase gradually 1-3 hours after irradiation while on the contrary the activities of cardiac muscle and bone marrow are found to have decreased markedly 3-6 hours afterwards. Later on the activities of the liver, spleen, kindney and peripheral blood decrease again and after 6-12 hours they show the values below the normal, whereas after 12-24 hours, they recover close to the normal value excepting three cases in perihperal blood. The activities of cardiac mucle and bone marrow decrease for the first 3-6 hours but later increasing gradually, they recover almost to the normal 12-24 hours afterwards. However, after 12 hours the activity of bone marrow declining Gradually, continues its descent without ever recovering. Although the activity of mitochondrial ATP-ase behaves more or less in similar manner as that of myosin ATP-ase, its absolute value is lower than the latter observed at the same time and the former has a tendency to fluctuate prior to the latter. In histochemical observations the intensity of reactions fluctuates rather identically with the fluctuations observed in biochemical study. The reaction of cardiac muscle is markedly reduced for the first three hours after irradiation but it can be somewhat reactivated with cysteine. After six hours the reactions of liver parenchymal cells, biliary tubules, and basillar part of epithelial cells of renal urinary tubules decrease to a certain degree; and this decrease seems to be due to the true ATP-ase activities controlled by the SH group. The reaction of phosphomonoesterase like ATP-ase receiver no conceivable influence with X-ray irradiation. A decrease in the numbers of leukocytic cells is responsible for the striking reduction in the activity of the spleen 12 hours after irradiation. When the liver, kidney and heart in normal conditions are made to react in the absence of substrate, they show extremely slight reaction; whereas after X-ray irradiation, invariably they reveal no such reaction. en-copyright= kn-copyright= en-aut-name=OhtaniKyohichiro en-aut-sei=Ohtani en-aut-mei=Kyohichiro kn-aut-name=大谷恭一郎 kn-aut-sei=大谷 kn-aut-mei=恭一郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部病理学教室 END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=2 article-no= start-page=413 end-page=430 dt-received= dt-revised= dt-accepted= dt-pub-year=1958 dt-pub=19580228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Biochemical and Histochemical Studies on ATP-ase Activities of Blood and Tissue Cells Part 1. Observations on Normal Mice and Rabbits kn-title=血球及び組織細胞のATP-ase活性に関する生化学的並びに組織化学的研究第1編 正常マウス及び家兎に於けるATP-ase活性について en-subtitle= kn-subtitle= en-abstract= kn-abstract=Adenosin-triphosphate (ATP) was obtained from the skeletal muscle of rabbits and dogs with Lohmann's method as Ba-salt. Before use this was changed to Na-salt which was proved to be pure chromatographically. Using this Na-salt as substrate observation on ATP ase activity were carried out in tissues of the liver, spleen, heart, kedney, duodenum and skeletal muscles as well as in blood and bone marrow of rabbits. Chemical analysis proved that various organs and tissues gave myosin ATP-ase activity showing the values specific to each organ, i.e. about 10γPi per 100 mg. of wet tissues of heart muscle, liver, spleen, kidney and duodenum, 6γPi per 100 mg. in bone marrow, quite a low value of about 1γPi per 100 mg. in circulating blood. In every organ the activity of mitochondrial ATP-ase was as low as 0.9-10.3γ Pi per 100 mg., quite lower than that of myosin ATP-ase; and as for the differences between the values of myosin and mitochondrial ATP-ases in each organ, it was found that the difference was smallest in peripheral blood and greatest in the heart tissue. As for the practical application in the histochemical study, frozen slices of formalin fixation are thought to be the simplest and best. According to their reactions against activating agents (cysteine) and inhibitory agents (PCMB), ATP-ase acn be divided into four types. The first type is of the typical ATP-ase which is demonstrable only in the frozenslices of cardiac and skeletal muscles, and detected especially in the region of anisotropic disk. This reaction is inhibited by PCMB and reactivated by cysteine. The second type is of those found in frozen slices of basillar part of epithelial cells of renal urinary tubules, liver parenchymal cells and biliary tubules and mooth muscle of duodenel wall. This reaction is inhibited by PCMB but not reactivated by cysteine. The third type is of those appear at the brush border of epithelial cells of renal urinary tubules of paraffin sections. This reaction is markedly inhibited by cysteine but stands unaffected by PCMB. The fourth type is of those detectable in various portions of tissues such as the smooth muscle of arterial media and intima as well as various viscera. The reaction remins unaffected either by cysteine or PCMB in both the frozen and the paraffin sections. The reaction of blood cells is the one that rightly belongs to this type. Reactions observable in paraffin sections are the enzyme actions mainly belonging to the third and the fourth types; and it is believed the reaction due to phosphomoesterase (Vrd tpye) and the unknown enzymes other than true ATP-ase (Wth type). In the case of the slices embedded in methacryleric resin all activities excepting that of the brush border of epithelial cells of renal urinary tubules are lost. The ATP-ase activity of leukocytes is found chiefly in the cytoplasm and it is detected in matured cells to a marked degree. en-copyright= kn-copyright= en-aut-name=OhtaniKyohichiro en-aut-sei=Ohtani en-aut-mei=Kyohichiro kn-aut-name=大谷恭一郎 kn-aut-sei=大谷 kn-aut-mei=恭一郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部病理学教室 END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1-3 article-no= start-page=307 end-page=312 dt-received= dt-revised= dt-accepted= dt-pub-year=1962 dt-pub=19620330 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effect of unsaturated high fatty acid fraction extracted from X-ray irradiated rabbit liver (OX) on the mitochondrial swelling of normal rat liver kn-title=X-線照射家兎肝より抽出した高級不飽和脂肪酸分画により惹起されたmitochondriaのswellingに関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effects of OX, a high unsaturated fatty acid fraction extracted from x-ray irradiated rabbit liver, on rat liver mitochondrial swelling was studied and following results were obtained. 1) Strong swelling action is demonstrated at OX concentration above 0.001% in 0.15KCl solution. 2) Swelling action on mitochondria is reduced by sucrose but not changed by sodium succinate. On the other hand, serum albumin and ATP inhibit completely mitochondrial swelling. 3) Mitochondrial swelling caused by OX is reversed by serum albumin and ATP. The intensity of contraction is found in the following order containing ATP, ATP+Mg and ATP +Mg+serum in the media. 4) M itochondrial swelling is induced by 0.005% OX in the substrate of succinate but respiration is not largely prevented. 5) The incorporation of P(32) into Δ10P of swollen mitochondria is almost completely inhibited by OX. en-copyright= kn-copyright= en-aut-name=UrakamiHiroyuki en-aut-sei=Urakami en-aut-mei=Hiroyuki kn-aut-name=浦上博之 kn-aut-sei=浦上 kn-aut-mei=博之 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部附属癌源研究代謝部門 END start-ver=1.4 cd-journal=joma no-vol=77 cd-vols= no-issue=7 article-no= start-page=1095 end-page=1111 dt-received= dt-revised= dt-accepted= dt-pub-year=1965 dt-pub=19650730 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Experimental Studies on Cancer Report 1. Studies on the influences of several antitumor agents upon Bashford carcinoma by tissueculture kn-title=癌に関する実験的研究 第1編 Bashford癌培養細胞に及ぼす各種抗癌剤の影響 en-subtitle= kn-subtitle= en-abstract= kn-abstract=For different antitumor agents, Nitromin, thio-TEPA, Mitomycin C, and Chromomycin were added in various concentrations into roller tube culture of Bashford carcinoma cells, and thier influences upon the cellular morphology were studied by phase contrast microscopy and by stained preparations. The results obtained are as follows. 1. The minimil growth-inhibiting concentrations of Nitromin, thio-TEPA, Mitomycin C and Chromomycin were 1 r/ml, 0.5 r/ml, 0.01 r/ml and 0.01 r/ml, respectively. 2. The morphological alterations of Bashford carcinoma cells induced these antitumor agents at and around the minimal growth inhibiting concentrations included the following: (a) Nitromin caused dissociation of cells, nuclear alterations and appearance of "inclusion cells" in many cells, (b) thio-TEPA induced rupture of mitochondria and multinucleated giant cells, (c) Mitomycin C was mainly associated with cytoplamic changes such as vacuolization, mitochondrial rounding and cytoplasmic fusion, (d) Chromomycin was destructive to both nucleus and cytoplasm leading to the nuclear pycnosis and rupture of the cell membranes 3. The roller tube culture technique of Bashford carcinoma cells was considered an excellent system for the in vitro screening of antitumor agents. en-copyright= kn-copyright= en-aut-name=KugaRyosuke en-aut-sei=Kuga en-aut-mei=Ryosuke kn-aut-name=陸亮介 kn-aut-sei=陸 kn-aut-mei=亮介 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部平木内科教室 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=4-6 article-no= start-page=193 end-page=200 dt-received= dt-revised= dt-accepted= dt-pub-year=1964 dt-pub=19640630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=An apparatus for simultaneous measurement of 90° light scattering, pyridine nucleotide fluorescence and oxygen consumption of mitochondria kn-title=Mitochondria の90°光散乱,pyridine nucleotide の螢光及び酸素消費量変化の同時測定装置の試作 en-subtitle= kn-subtitle= en-abstract= kn-abstract=An apparatus for simultaneous measurement of 90° light scattering, pyridine nucleotide fluorescence and oxygen consumption of mitochondria was designed and constructed for the purpose to study the mitochondrial structure and function. Oxygen consumption was measured by rotating platinum eleotrode by the modification of Hagihara's method, attached in the cell of the apparatus. Mitochondrial swelling and shrinkage were measured by 90° light scattering at 650mμ. The monochrome light was made by plism monochromator and was led to the cell of the apparatus. Scattered light of 650mμ at 90° was filtered through the filter trasmitting 650mμ, excluding visual and ultra-violet radiation under 600mμ. Then the scattered light was registered by photomultiplier tube 1P22 which is a good choice for measurement of the light near red end of spectrum. Relative reduced pyridine nucleotide concentration was measured by fluorometry. Fluorometer was constructed as follow: For excitation, a bright light at 365mμ line of marcury lamp was isolated from other bright light by passing through the Hitachi interference filter (365mμ) or Corning No. 7-54 (9863) which transmits ultraviolet light and excludes visual radiation above 410mμ and was led to the cell by half mirror at a position of light path between the monochromator for 90° light scattering and the cell. The fluorescence light was passed through the filter of Corning No. 3-73 (3389) which transmits visual radiation at approximately 440mμ. Then the fluorescence intensity in the spectral interval set by the grating monochromator was registered by photomultiplier 1P21 which has good signal-to-noise ratio, and is suitable for measurements of compounds that fluoresence between 350 and 650mμ. The scattered light at 650mμ was not affected by excitation light and fluorescence light, and fluorescence intensity was not by scattered light at 650mμ. The simultaneous measurements of the oxidation-reduction of p ridine nucleotides, the respiration states and the change of 90° light scattering is given as an example of the performance of the present apparatus. en-copyright= kn-copyright= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name=内海耕慥 kn-aut-sei=内海 kn-aut-mei=耕慥 aut-affil-num=1 ORCID= en-aut-name=YamamotoGoki en-aut-sei=Yamamoto en-aut-mei=Goki kn-aut-name=山本剛禧 kn-aut-sei=山本 kn-aut-mei=剛禧 aut-affil-num=2 ORCID= en-aut-name=UrakamiHiroyuki en-aut-sei=Urakami en-aut-mei=Hiroyuki kn-aut-name=浦上博之 kn-aut-sei=浦上 kn-aut-mei=博之 aut-affil-num=3 ORCID= en-aut-name=NishikazeKeiko en-aut-sei=Nishikaze en-aut-mei=Keiko kn-aut-name=西風桂子 kn-aut-sei=西風 kn-aut-mei=桂子 aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部癌研代謝部 affil-num=2 en-affil= kn-affil=岡山大学医学部癌研代謝部 affil-num=3 en-affil= kn-affil=岡山大学医学部癌研代謝部 affil-num=4 en-affil= kn-affil=岡山大学医学部病理学教室 END start-ver=1.4 cd-journal=joma no-vol=76 cd-vols= no-issue=1-3 article-no= start-page=13 end-page=19 dt-received= dt-revised= dt-accepted= dt-pub-year=1964 dt-pub=19640330 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Changes of structure and function of mouse liver mitochondria after whole body irradiation kn-title=X線全身照射にともなうマウス肝ミトコンドリアの機能と形態の変動 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mechanism of X-ray irradiation on the function and structure of mitochondria was studied by analysis of mitochondrial swelling-shrinkage, oxidative phosphorylation, Fe ions induced swelling, and Fe ions induced lipid peroxidation. Mitochondria were isolated from the livers of mice at 3, 6, 12, 24 and 48 hours after whole body irradiated 500r with X-ray, and from non-irradiated mice. The results of the experiment are as follow: 1. The activity of oxidative phosphorylation of mitochondria was reduced by 50 per cent after irradiation for 6 hours and returned to normal after 24 hours. 2. Respiratory control of mitochondria was decreased by 40 per cent after irradiation for 6 hours and remained at this low level for 48 hours. 3. The degree of swelling-shrinkage of mitochondria (about 20 per cent changes in volume) measured by 90° light scattering was reduced to some extent during 6 to 12 hours after irradiation and then recovered to control level after 24 hours. 4. The large amount of mitochondria to show the certain extent of 90° light scattering was required at 6 hours after X-irradiation and returned to normal after 48 hours. 5. Swelling, measured by the absorbancy at 520mμ, and lipid peroxidation of mitochondria induced by Fe ions were increased in there initial velocity and in there extent by X-irradiation. These increments were maximum at 12 hours. 6. These results suggest that the increment of peroxidizable lipid of mitochondria is a fact for the uncoupling of oxidative phosphorylation with X-irradiation, The possible role of uncoupling of oxidative phosphorylation by X-irradiation has been discussed. en-copyright= kn-copyright= en-aut-name=UrakamiHiroyuki en-aut-sei=Urakami en-aut-mei=Hiroyuki kn-aut-name=浦上博之 kn-aut-sei=浦上 kn-aut-mei=博之 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部癌源研究施設代謝部 END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=9-10 article-no= start-page=905 end-page=913 dt-received= dt-revised= dt-accepted= dt-pub-year=1968 dt-pub=19681030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Soluble Proteins of the Rats Transplanted with Walker Carcinoma Part I. The Neutral Lipids in Nucleus and Mitochondrial Fractions of Liver, Spleen and Tumor kn-title=Walker carcinoma移植ラッテ組織中の可溶性蛋白に関する研究 第1編 肝,脾および腫瘍の核ならびにミトコンドリア画分における中性脂質について en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lipids combined with soluble proteins in nucleus and mitochondrial fractions of the liver, spleen and tumor of rats bearing Walker carcinoma were compared with those of normal rats by analysis on thin layer chromatography. The tumor used in the experiment was about one per cent of the body weight. 1) The extracting solutions used in the experiment, 1/15M phosphate buffer, 0.4M NaCl were better than 0.1M acetate buffer and 0.1N NaOH. 2) Proteins per wet tissue weight were increased slightly both in liver and spleen. Tumor had more protein than that of the normal liver. 3) Total lipids per protein were increased slightly in the spleen but decreased in the liver, those of the tumor were higher than that of the normal liver. Triglyceride probably had important role on the results. en-copyright= kn-copyright= en-aut-name=ShinzekiKen en-aut-sei=Shinzeki en-aut-mei=Ken kn-aut-name=新関顕 kn-aut-sei=新関 kn-aut-mei=顕 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部附属病院第一外科教室 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=11-12 article-no= start-page=1009 end-page=1015 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=19671230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Clinical Studies on Plasma Levels of Liver Enzymes Part. U Plasma Levels of Cytoplasmic and Mitochondrial Enzymes in Rats with Acute Liver Injury and Patients with Various Liver Diseases kn-title=肝酵素の血中遊出動態に関する臨床的研究 第2編 肝障害時における肝細胞上清およびミトコンドリア局在酵素の血中遊出について en-subtitle= kn-subtitle= en-abstract= kn-abstract=The plasma levels of isocitric dehydrogenase (ICD), glutamic-pyruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT) and glutamic dehydrogenase (GLD) were studied in rats with per oral doses of 0.2ml/100g B. W. of carbon tetrachloride in a 25 % mixture with olive oil and in patients with various liver diseases. Mitochondrial GOT in serum was separated by DEAE-cellulose column chromatography. 1) The elevation in the serum levels of GOT, GPT and ICD from cytoplasma occurred before the onset of parenchymal cell necrosis of the liver in a histologic sense in rats with CCl(4) poisoning. Uniform elevation in the serum levels of the enzymes from both fractions of cytoplasma and mitochondria of liver cell was found in acute icteric period of viral hepatitis as well as in rats in 12 hours to 48 hours with CCl(4) poisoning. In the case of active chronic hepatitis the elevation in serum levels of GOT, GPT and ICD from cytoplasma was predominant as compared with relatively low elevation of mitochondrial GLD. 2) The distinct elevation in serum level of mitochondrial GLD in liver cirrhosis and intrahepatic cholestasis were characteristic as compared with relatively low elevation of the cytoplasmic enzymes in these cases. It is noteworthy that these results reflect sensitively the intracellular lesions in liver diseases. 3) Mitochondrial GOT could be demonstrated only in a remarkable increase of serum GOT levels in the initial stage of acute hepatitis as well as in the exacerbating stage of active chronic hepatitis. On the other hand, in cases of cholestatic liver diseases and cirrhosis no mitochondrial GOT was detected in serum, while another mitochondrial enzyme GLD showed a high plasma level. en-copyright= kn-copyright= en-aut-name=SanoYoshihide en-aut-sei=Sano en-aut-mei=Yoshihide kn-aut-name=佐野良英 kn-aut-sei=佐野 kn-aut-mei=良英 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第一内科教室 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=11-12 article-no= start-page=1003 end-page=1008 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=19671230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Clinical Studies on Plasma Levels of Liver Enzymes Part. T Electrophoretic Patterns of Serum GOT in Rats with Acute Liver Injury and Patients with Various Liver Diseases kn-title=肝酵素の血中遊出動態に関する臨床的研究 第1編 肝障害時における血清GOTの電気泳動patternについて en-subtitle= kn-subtitle= en-abstract= kn-abstract=The present study was conducted with the aim to elucidate the mechanism of transaminase release into blood from damaged liver cells. Observations were made on the fluctuations of the transaminase activity in various cell fractions of the liver as well as on the changes of serum GOT-isozyme patterns in various diseases through quantitative analysis by means of starch electrophoresis. In the rats with acute liver injury there were increases of GOT and GPT activities in blood on one band and contrarily decreases of these in the liver cells on the other. The changes of the mitochondrial GOT and GPT activities, as judged from the decreasing rate, fairly parallel with those in the supernatant fraction. In the electrophoretic assay of serum GOT in these cases the elevations of the serum GOT activity is assumed to be most likely due to that in the supernatant fraction, but about 10% of the serum GOT can be considered to be released from the mitochondrial fraction at the stage that clearly showed necrosis under light microscpe. In the electrophoretic analysis of serum GOT obtained from patients with various liver diseases it has been observed that of the 10 cases of acute hepatitis showed an increase of the supernatant GOT with appearance of the mitochondrical GOT. In contrast liver cirrhosis showed no apperance of mitochondrial GOT. en-copyright= kn-copyright= en-aut-name=SanoYoshihide en-aut-sei=Sano en-aut-mei=Yoshihide kn-aut-name=佐野良英 kn-aut-sei=佐野 kn-aut-mei=良英 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第一内科教室 END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=7-8 article-no= start-page=647 end-page=663 dt-received= dt-revised= dt-accepted= dt-pub-year=1968 dt-pub=19680830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Brain Metabolism on Steroid Hormones kn-title=脳におけるコルチコイド代謝 en-subtitle= kn-subtitle= en-abstract= kn-abstract=By the clinical studies on steroid hormones in endogenous mental diseases so far carried out, we have found that it is the steroids belonging to 17-KS rather than 17-OHCS which are associated with the mental excitation. In view of this, we attempted a study about the brain metabolism on testosterone which is an important precursor of 17-KS with a strong biological activity. The materials used were the brain of Donryu rats and human beings. Each of these brain tissues was homogenized in ten-fold volumes of 1/15M phosphate buffer solution. Then, taking 2ml of the brain phosphate buffer homogenate or 2ml each of 1/15M phosphate buffer suspension of the supernatant containing nuclear, mitochondrial or microsomal fraction, prepared from 1g rat brain, the incubation was conducted in the air at 37℃ for 60 minutes after adding 0.1μc [4C(14)] testosterone, 0.2 mg cold testosterone, 0.5 mg each of NAD and NADP as cofactor, and 10 mg nicotinamide. Then, metabolites were extracted, applied on the florisil column, and 2% methanol-chloroform fraction was collected and dried. For the control groups the brain tissues inactivated by heating were employed. Each of the specimens thus obtained was applied on the Silicagel-G thin layer chromatography (TLC), and metabolites were isolated and identified by the 2% NGS gas chromatography. After the TLC-autoradiography the portions that coincided with the radioactive spots was taken and each of these chromatograms was applied to the liquid scintillation counter and the percentage of the conversion of metabolites was calculated from respective radioactivity. 1) Both from the rat brain and the human brain on the TLC (chloroform-acetone-methanol, 90:7:3, developed for 15 cm) there are seen four principal spots, and designating these spots as I, II, III and IV starting from the original point of application, the spot II is testosterone, proving that 90-95% or more of testosterone added has not been metabolized. 2) The spots I and III are minor metabolites, of which I is the substance like ll-OH-Etio-cholanolone. and III is an unknown substance. The conversion rate of each is only about 0.2%, proving to be of no significant value. 3) The spot IV is a major metabolite, and on the further TLC (chloroform-acetone, 85:15, developed for 55 cm) it separated itself into two spots, each of which has been identified to be Δ(4)-androstene-3, 17-dione and dihydrotestosterone. The conversion rate of the two together is 2.46% with the rat brain and 2.29±0.73% with the human brain in average, and without addition of co factors it is decreased to 1.80% and O.5% respectively. 4) The activity of the enzymes responsible for the major metabolite formation, namely, 17β-hydroxysteroid dehydrogenase and 5α-reductase, is detectable in every fraction of the rat brain, but it is highest in the telencephalon mitochondrial and fairly high in the supernatant fraction, and the conversion rate from testosterone is about 0.5% in each case. After all, since the brain is not a metabolic organ nor a target organ, the metabolism of testosterone is extremely low, nonetheless, looking it from the aspect of its potency, we cannot rule out its significance. A further problem which we have to solve will be the role played by the hormones responsible for mental excitation, by investigating the correlation of the brain site to the metabolism of steroids including testosterone. en-copyright= kn-copyright= en-aut-name=KikuiShigeru en-aut-sei=Kikui en-aut-mei=Shigeru kn-aut-name=菊井茂 kn-aut-sei=菊井 kn-aut-mei=茂 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部神経精神医学教室 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=11-12 article-no= start-page=891 end-page=902 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=19671230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Pyruvate Metabolism in Carbontetrachlorideintoxicated Rats U. Pyruvate Concentrations in the Liver and Blood in the Recovery from Carbontetrachloride Intoxication and the Effect of Pantethine, ATP and DPN kn-title=実験的四塩化炭素中毒におけるpyruvate代謝の研究 第2編 四塩化炭素中毒の回復期及び薬物負荷時の肝組織及び血液中pyruvateの変動 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The concentrations of pyruvate and related compounds in the liver and blood in the recovery of carbontetrachloride intoxication of rats were measured and the effects of pantethine, ATP and DPN administrations were studied. (1) In the recovery stage from acute carbontetrachloride intoxication, the first and fourth weeks after single subcutaneous administration of carbontetrachloride, and in the recovery stage from chronic carbontetrachloride intoxication, the second and fourth weeks after subcutaneous injection of carbontetrachloride twice a week for four weeks, serum transaminase activities (S GOT and S GPT) returned normal and the histological changes of liver (heamatoxylin-eosin staining) were also normal except for slight irregular cellular ridges and cytoplasmic basophilia. (2) Decreased pyruvate oxidation in the rat liver mitochondria was still present even though no significant histological changes could be demonstrated microscopically. This might mean that the function of mitochondrial enzymes would not be restored in a shorter time. In the first and fourth weeks of recovery from the acute intoxication, increases of the lactate/pyruvate ratio of the liver were observed. The pyruvate level in the liver did not show any significant change in the recovery from acute and chronic intoxications. (3) Intraperitoneal administration of pantethine (Bis (N-pantotenyl -β aminoethyl) disulfide), a precursor of coenzyme A, to carbontetrachloride-intoxicated rats arrested the progression of fibrosis and the formation of pseudoacinus of the liver. The diffuse fatty infiltration of the liver, however, was not prevented by pantethine. The fact that no improvement of the pyruvate-oxidizing activity (QO(2)) of liver mitochondria, a decrease of pyruvate level and an increase of cholesterol in the blood were observed with pantethine seems to suggest that the diffuse fatty infiltration of the liver by pantethine might be resulting from decreases of hepatic ATP level and -SH enzyme activities, which would be caused by pantethine administration. Pantethine improved other routine liver fanction tests except for Zinc sulfate test. (4) Simultaneous administration of pantethine and ATP reduced the extent of diffuse fatty infiltration of the liver. The blood sugar decreased by pantethine and ATP more than by pantethine alone probably due to an insulin like activity of ATP. The blood cholesterol increased, and QO(2) and other routine liver function tests were improved more by pantethine and ATP than by pantethine alone. (5) Intraperitoneal administration of DPN to carbontetrachloride-intoxicated rats resulted in marked improvements in liver histology, QO(2), lactate/pyruvate ratio of the liver and the other liver function tests. These results seem to suggest that the progression of the liver injury by carbontetrachloride depends largely on DPN contents. en-copyright= kn-copyright= en-aut-name=NakashimaMasao en-aut-sei=Nakashima en-aut-mei=Masao kn-aut-name=中島正男 kn-aut-sei=中島 kn-aut-mei=正男 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第一内科 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=11-12 article-no= start-page=879 end-page=889 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=19671230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Pyruvate Metabolism in Carbontetrachlorideintoxicated Rats T. The Effect of Carbontetrachloride Intoxication on the Levels of Pyruvate in the Liver and Blood kn-title=実験的四塩化炭素中毒におけるPyruvate代謝の研究 第1編 肝組織及び血液中Pyruvateに及ぼす四塩化炭素の影響 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Measurements of the concentration of pyruvate and related compounds in the rat liver and blood in carbontetrachloride intoxication revealed the follwing: (1) Main histological changes of rat liver produced by subcutaneous injection of carbontetrachloride twice a week were centrolobural fatty infiltration in the first week, slight reaction of mesenchymal cells and fibrosis of portal triad in the second week, progression of the fibrosis in the fourth week, formation of pseudoacinus in the sixth week, and appearance of nodural cirrhosis from the eighth to twelfth week. (2) The pyruvate concentration in the liver paralleled with that in the blood (r=1.24, p<0.05). The pyruvate concentration increased in acute stage of carbontetrachloride intoxication (the first week), reaching the maximum in the sixth week, when the marked fibrosis was observed in the liver histology. There after the pyruvate level decreased in the eighth and tenth weeks and increased again in the twelfth week. (3) The pyruvate-oxidizing activity of rat liver mitochondrial fraction (QO(2)) decreased approximately half in the acute stage (the first week) of carbontetrachloride intoxication and below one tenth in most cases after the eighth week. Since a significant negative correlation between the pyruvate concentration and the QO(2) value was found until the fourtn week, the increase in the liver and blood pyruvate might be caused mainly by the disturbance of pyruvate oxidation in the rat liver mitochondria. (4) The negative correlation between the pyruvate and QO(2) became weak after the sixth week of carbontetrachloride intoxication. In the latter stages the lactate concentration of liver increased more than that in the acute stage. Consequently, the lactate/pyruvate ratio and hence the total pyruvate lactate pool of the liver increased more. For the explanation of the increased lactate level and the lactate/pyruvate ratio, it is considerable that a local hypoxia may develop as a result of the disturbance in liver circulation caused by a repetition of degeneration and regeneration of liver cells, and the hypoxia would accelerate glycolysis in the liver and at the same time decrease the oxidation of DPNH as well as that of pyruvate. The increase of pyruvate level and the decrease of lactate/pyruvate ratio in the twelfth week, when liver injury advanced progressively, could be accounted for by the extreme disturbance of oxidation and by a suppression of glycolysis which would exist in the latter stage. Although the metabolism of pyruvate in the liver tissue is easily influenced by hypoxia, as suggested by the changes in lactate/pyruvate ratio and total pyruvate-lactate pool size, the pyruvate level in the blood does not seem to reflect these metabolic changes of the liver sensitively enough. (5) Blood sugar levels decreased in accordance with the advance of liver injury. The decrease of blood sugar may be caused by a disturbance of reguratory mechanism of blood sugar by the liver. en-copyright= kn-copyright= en-aut-name=NakashimaMasao en-aut-sei=Nakashima en-aut-mei=Masao kn-aut-name=中島正男 kn-aut-sei=中島 kn-aut-mei=正男 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第一内科 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=9-10 article-no= start-page=763 end-page=770 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=19671030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Amino Acid and Protein Metabolism of the Brainwith the Use of [U-(14)C]-Glucose 2. A Study on the Amino Acid Metabolism in Normal Cat Brain and the Brain Under Subacute Compression of the Cats Under Nembutal Anesthesia kn-title=U-(14)C-グルコースを用いた脳のアミノ酸タンパク代謝の研究 第2編Infusion法及び脳灌流法による正常ネコ脳と亜急性圧迫ネコ脳のネンブタール麻酔下におけるアミノ酸代謝について en-subtitle= kn-subtitle= en-abstract= kn-abstract=In the previous paper dealing with the protein metabolism as well as the structural chemical aspects of the brain proteins in normal cat brain and the brain under chronic compression by means of infusion method, it was reported that organic changes of the brain affect the protein metabolism. This communication briefly describes the results of the experiment conducted by the infusion method on the amino acid metabolism studied with the use of [U-(14)C]-glucose while comparing with the same metabolism in normal cat brain. Further the effect of the functional changes mainly induced by Nembutal on the glucose metabolism in the brain was studied by means of brain perfusion. and this effect was compared with the effect of Nembutal anesthesia as studied by infusion method. The study was also focused on the metabolism of glutamic acid and aspartic acid which are the protein components of crude mitochondrial fractions in the brains of those placed under subacute compression and normal cat brain. After the infusion of [U-(14)C]-glucose, the incorporation of (14)C to free glutamic acid and aspartic acid of the brain was higher in the brain under subacute compression than in normal brain, i.e. the relative specific activity (RSA) was higher in the former than in normal brain. This tendency was more marked in aspartic acid. In observing the glucose metabolism by injecting Nembutal into carotid artery during the brain parfusion, the metabolic pattern at this stage showed a pattern intermediate between that during the high functional state and the low functional state of the brain under perfusion. This resembles the metabolic rates of glutamic acid and aspartic acid of the normal cat brain under a slight anesthesia by the infusion method. Only in the case of aspartic acid the relative specific acitivity (RSA) in the brain during the infusion was considerably lower than RSA during brain perfusion under the influence of Nembutal. In the protein component amino acid metabolism of crude mitochondrial fractions. RSA of the protein component glutamic acid was higher under subacute compression state than RSA of normal brain. en-copyright= kn-copyright= en-aut-name=OmoriBuntaro en-aut-sei=Omori en-aut-mei=Buntaro kn-aut-name=大森文太郎 kn-aut-sei=大森 kn-aut-mei=文太郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部神経精神医学教室 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=9-10 article-no= start-page=751 end-page=762 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=19671030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Amino Acid and Protein Metabolism of the Brainwith the Use of [U-(14)C]-Glucose 1. Protein Metabolism of Normal Cat Brain and the Brain Under Chronic Compression by Infusion Method kn-title=U-(14)C-グルコースを用いた脳のアミノ酸タンパク代謝の研究 第1編 Infusion法によるネコにおける正常脳と慢性圧迫脳のタンパクについて en-subtitle= kn-subtitle= en-abstract= kn-abstract=There are many reports on the protein metabolism of the brain but it seems that much remains to be clarified as regards the structural chemistry of the brain proteins. For the purpose to elucidate this problem, the author studied histological changes in the cat brain at the time when the frontal lobe was placed under chronic compression by the extradural compression method of Ishii et al., and simultaneously studied the incorporation of (14)C into each subcellular unit protein of the brain tissue after intravenous infusion of [U-(14)C]-glucose. Further, the incorporation of (14)C into what Otsuki et al. call acid-ethanol soluble proteins and residual proteins was investigated. Brain proteins were fractionated by DEAE Sephadex column chromatography as well as by the disc-electrophoresis with polyacrylamide gel, and compared these fractions with these of normal cat brain. The results of the study are briefly summarized as follows. High molecular substances of the mitochondrial fractions of the cat brain under the chronic compression showed a higher relative specific activity (RSA) to the blood glucose than those of the normal cat brain. In the case of acid-ethanol soluble proteins in the brain under chronic compression, just as in the case of normal cat brain, particulate fractions, especially crude mitochondrial fractions, revealed a higher incorporation of (14)C, and also their RSA was higher than that in normal brain. In the fractionation by DEAE-Sephadex column chromatography, the mitochondrial fractions of the brain under chronic compression showed a specific peak of the eluate that dissolved with 0.8 M NaCl. This substance was the protein fraction that showed the mobility identical with prealbumin fraction obtained by the dis-electrophoresis with polyacrylamide gel. Looking at the (14)C incorporation by each protein fraction separated on DEAE-Sephadex column, the radioactivity was observable in the portion dissolved only by 0.02 M sodium phosphate buffer. This substance, when subjected to the disc-electrophoresis with polyacrylamide gel, showed the mobility identical with γ-globulin fraction. en-copyright= kn-copyright= en-aut-name=OmoriBuntaro en-aut-sei=Omori en-aut-mei=Buntaro kn-aut-name=大森文太郎 kn-aut-sei=大森 kn-aut-mei=文太郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部神経精神医学教室 END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=3-4 article-no= start-page=313 end-page=318 dt-received= dt-revised= dt-accepted= dt-pub-year=1968 dt-pub=19680430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=(4)-Cholestenone Metabolism in Rat Liver Transplanted with Walker Carcinoma Part2. Studies on enzymic activity of (4)-cholestenone metabolism in tumor-bearing rat liver kn-title=WALKER CARCINOMA移植RATにおける(4)-CHOLESTENONE-4-C(14)の代謝 第2編 肝の酵素分画による代謝 en-subtitle= kn-subtitle= en-abstract= kn-abstract=(4)-Cholestenone-4-C(14) metabolisms were studied with the nuclear, mitochondrial, microsomal and supernatant fraction. Enzymic activity of cholestenone to cholestanone was higher in nuclear and mitochondrial fraction, and the activity was higher about 2-4 times in tumor-bearing rat. This suggests the enzyme block from cholestenone to cholestanone. Inaceton powder, these enzymes were inactivated, and the enzymes were easisted in the fraction precipitated with the concentration of (NH(4))(2)SO(4) at 30g/dl. en-copyright= kn-copyright= en-aut-name=AizawaTadashi en-aut-sei=Aizawa en-aut-mei=Tadashi kn-aut-name=會沢禎 kn-aut-sei=會沢 kn-aut-mei=禎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部附属病院第一外科教室 END start-ver=1.4 cd-journal=joma no-vol=80 cd-vols= no-issue=1-2 article-no= start-page=279 end-page=287 dt-received= dt-revised= dt-accepted= dt-pub-year=1968 dt-pub=19680228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The Transformation of Energy Metabolism during the Maturation of Reticulocytes 1. The Changes of Acid Soluble Nucleotides during the Maturation of Reticulocytes kn-title=網赤血球の成熟過程におけるエネルギー代謝の変換 第一編 網赤血球の成熟と酸溶性ヌクレオチドの変化 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In an attempt to clarify the process of transformation in energy metabolism during the reticulocytes maturation, the changes of acid soluble nucleotides during the maturation in vitro were analysed column chromatographycally and the following results were obtained: 1. The acid soluble nucleotides of reticulocytes were mainly composed of cytidine monophosphate, nicotinamideadenine dinucleotide, adenosine monophosphate, inosine monophosphate, adenosine diphospbate, guanosine diphosphate, adenosine triphosphate and guanosine triphosphate. In such nucleotide components the purine nucleotide compounds were composed of 70 to 80% of whole nucleotides. 2. During the maturation in vitro nucleotides and adenosine triphosphate contents decreases but the ultra-vioiet absorbing materials as a whole increases with the increases of base and nucleoside contents. 3. The changes of acid soluble nucleotides during the maturation were stimulated by 2, 4-dinitropbenol or antimycin A. 4. The accumualation of hypoxanthine during the maturation was stimulated by adding 2, 4-dinitrophenol or antimycin A which inhibited the RNA degradation, accopaning with the degradation of acid soluble nucleotides. 5. The reticulocyte maturation, the RNA degradation is largely dependent on energy from the mitochondrial oxidative phosphorylation. en-copyright= kn-copyright= en-aut-name=HayashiKenji en-aut-sei=Hayashi en-aut-mei=Kenji kn-aut-name=林健二 kn-aut-sei=林 kn-aut-mei=健二 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部病理学教室 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3-4 article-no= start-page=271 end-page=280 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=19670430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Malic Dehydrogenese Isozyme Part U. A Study on Malic Dehydrogenese Isozymes of Human Serum and Rat organs during Development kn-title=リンゴ酸脱水素酵素のアイソザイムに関する研究 第2編 ヒト血清及び発育過程におけるラット臓器のリンゴ酸脱水素酵素アイソザイムについて en-subtitle= kn-subtitle= en-abstract= kn-abstract=Malic dehydrogenese (MDH) activities in human serum of various diseases were studied. Elevation of MDH activities were observed in myocardial infarction, acute hepatitis, and some malignant tumors. Characteristic MDH isozyme patterns were obtained from serum of patients with myocardial infarction and acute hepatitis showing marked elevation of MDH activities. During the tetrazolium procedure for staining of electrophoreticaly separated serum malic or lactic dehydrogenese isozymes on agargel, without substrate and co-enzyme, two peaks were noticed and named serum "non-specific factor". These peaks were considered a kind of non specific reactions which resulted from a reduction of the tetrazolium salt electrostaticaly adsorbed on Alb. 〜 α(1), Glb. by SH-groups of these serum proteins. These reactions were accelerated by the elavation of PH or the temperature, exposure during staining and the prolonged staining time, as well as the rise of concentrations of NTB, PMS and CN- in the staining medium. Considering of optimal conditions of enzyme reaction, the minimum use of NTB, PMS and Na CN, washing stained agargels with PH 4.5 acetic acid SoL, and complete shading during procedure could minimize the influence of this factor. Two MDH isozymes were demonstrated in agargel isozymograms of rat organs, one migrating towards the cathod and the other toward the anode. The cathodal fraction was considered mitochondrial MDH (m-MDH), and the anodal one cytoplasmic MDH (c-MDH), respectively. During development, m-MDH showed marked increase in heart muscle. In contrast to this, cMDH of liver and gastric mucosa increased in procedure of development. On the other hand the ratio of m-MDH and c-MDH in kidney remained constant through development. en-copyright= kn-copyright= en-aut-name=TakayasuMasao en-aut-sei=Takayasu en-aut-mei=Masao kn-aut-name=高安正雄 kn-aut-sei=高安 kn-aut-mei=正雄 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部平木内科教室 END start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=3-4 article-no= start-page=259 end-page=270 dt-received= dt-revised= dt-accepted= dt-pub-year=1967 dt-pub=19670430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Malic Dehydrogenese Isozyme Part T. A Study on Malic Dehydrogenese Activities and Isozymes of Various Human Organs kn-title=リンゴ酸脱水素酵素のアイソザイムに関する研究 第1編 ヒト各種臓器のリンゴ酸脱水素酵素活性及びアイソザイムについて en-subtitle= kn-subtitle= en-abstract= kn-abstract=Malic dehydrogenese (MDH) activities and isozymes of various human organs were measured. The assays of isozyme were carried out by means of agargel electrophoresis. The highest MDH activity was demonstrated in heart muscle. Liver, skeletal muscle, kidney and brain showed considerably high MDH activities. Six fractions were distinguished in many MDH isozymograms. In order of movility towards the cathod, each MDH isozyme was named MD(1), MD(2)…MD(6). Intracellular distribution of each MDH isozyme was investigated by means of cell fractionation, and MD(1)〜MD(5) were confirmed mitochondrial, MD(6) cytoplasmic, in origin. MDH isozyme-patterns of human organs were divided into 3 groups according to the ratio of mitochondrial MDH (m-MDH) and cytoplasmic MDH (c-MDH). Group T (m-MDH>c-MDH): heart muscle, kidney, skeletal muscle, white blood cell, red blood cell and lung-tissues. Group U (m-MDH≒c-MDH): liver, pancreas. Group V (This group situates between Group T and Group U): brain, gastric mucosa, and spleen. Studies on inhibitory effect of p-chlor-mercuri-benzoate (PCMB) on each MDH isozyme and heat stability of each MDH isozyme demonstrated that m-MDH was not inhibited by PCMB and stable to a heat test at 50℃ for 30,' when 1-malate was used as substrate. It was also observed that m-MDH was activated by a high concentration of 1-malate. According to the standard deviation of MD(6) and MD(3) activites, c-MDH considered regulatory enzyme and m-MDH constitutive enzyme, respectively. en-copyright= kn-copyright= en-aut-name=TakayasuMasao en-aut-sei=Takayasu en-aut-mei=Masao kn-aut-name=高安正雄 kn-aut-sei=高安 kn-aut-mei=正雄 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部平木内科教室 END start-ver=1.4 cd-journal=joma no-vol=82 cd-vols= no-issue=5-6 article-no= start-page=231 end-page=248 dt-received= dt-revised= dt-accepted= dt-pub-year=1970 dt-pub=19700630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Localization and Properties of DNA Molecules in the Mitochondria of Tumor Cells kn-title=腫瘍細胞のミトコンドリア内におけるDNA分子の局在と性状の研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=1. Electron microscopic observations were made on DNA fibers in the mitochondria of tumor cells induced by various kinds of DNA viruses, RNA viruses, and chemical carcinogens, and also in those of normal and regenerating rat livers and cultured liver cells. Intramito-chondrial DNA fibers were observed most frequently in the sectioned specimens of adenovirus type 12-induced or SV 40-induced hamster tumor cells, but were hardly observed in normal and regenerating liver cells and other tumor cells. 2. The DNA fibers disappeared by treatment with DNase, but not with RNase. 3. The DNA fibers in adenovirus-induced tumor cells were easily isolated by osmotic shock and observed as circular DNA molecules by rotary shadowing with the electron microscope, while DNA molecules were hardly isolated from rat liver mitochondria by the same treatment. 4. On the ultracentrifugal fractionation of sonically disrupted adenovirus-induced tumor mitochondria, DNA were found to be contained mostly in the supernatant fraction by chemical analysis and by electron microscopic observation. 5. DNA fibers observed in the mitochondrial matrix in the sectioned specimens were proved to be identical with the isolated circular DNA molecules. 6. On the ultracentrifugal fractionation of sonically disrupted rat liver mitochondria, DNA were found to be contained mostly in the membrane fractions by chemical analysis. However, DNA molecules were difficult to observe with the electron microscope in the sectioned specimens of the rat liver mitochondrial membrane fractions. Nevertheless, they were isolated by phenol extraction from the membrane fractions, and were observed as circular DNA molecules with the electron microscope. 7. Appearance of the DNA fibers in the mitochondrial matrix seems to be associated with the division cycle of mitochondria, and in the mitochondria where DNA fibers are not observed in the sectioned specimens, the DNA molecules are supposed to be hidden by firmly attaching to the inner membrane, and to be isolated by chemical extraction. en-copyright= kn-copyright= en-aut-name=TsukamotoHiromichi en-aut-sei=Tsukamoto en-aut-mei=Hiromichi kn-aut-name=塚本博通 kn-aut-sei=塚本 kn-aut-mei=博通 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部癌研生化学部 END start-ver=1.4 cd-journal=joma no-vol=84 cd-vols= no-issue=9-10 article-no= start-page=307 end-page=320 dt-received= dt-revised= dt-accepted= dt-pub-year=1972 dt-pub=19721030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Study on Cell Membrane Structure by Circular Dichroism -Changes in the protein structure after chemical fixation of mitochondrial particles, red cell membrane and bovine serum albumin, as well as a proposal for a cell membrane model- kn-title=細胞膜構造の円偏光二色性による研究 ミトコンドリヤ,赤血球膜および牛血清アルブミンの化学的固定によるタンパク質構造の変化と細胞膜モデルの考察 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recently, as the secondary structure of protein structure has come to be distinctly reflected by the ultraviolet circular dichroism (CD) spectrum, an attention has been called to the protein structure of cell membrane by circular dichroism. Lenard and Singer have demonstrated by CD spectrum that the chemical fixation of the cell membrane induces changes in the structure of native red cell membrane, but it is not clear whether or not their conclusion is applicable in common to the membrane of other cells. One of the objects of the present study was to clarify whether the conclusion of Lenard-Singer can be applied generally. For this purpose the author studied changes in the protein structure occurring after the chemical fixation of mitochondrial particles of the rabbit liver and rabbit red cell membrane and bovine serum albumin. It seems quite significant to elucidate the general applicability of their conclusion by clarifying the conformational changes in cell membraneous proteins and other proteins induced by the chemical fixation as it would offer a great parameter to grasp the molecular structure of native cell membrane. The second objective was to elucidate the specific phenomenon, i.e. the cause of red shift of the cell membrane, by the circular dichroism. On the basis of the findings obtained in the observations of those changes occurring in mitochondrial particles, red cell membraines and bovine serum albumin after the chemical fixation, the author proposes here a dynamic cell membrane model as suggested by Seno. The results of the study may be briefly summarized as follows. 1) In the investigation of spectra of the BSA fixed with formaldehyde it has been clearly demonstrated that the aggregation of protein molecules induces the red-shift of the CD spectrum confirming the theory of Lenard-Singer to be valid. 2) Of the findings reported by Lenard-Singer, the facts that chemical fixation induces about 30% (corrected value, 50% ) adhesion of helical structure to the cell membrane, and that the chemical fixation with KMnO(4) brings about the loss of 100% helical structure of the membraneous protein molecules were also demonstrated similarly in the rabbit liver mitochondrial particles and rabbit red cell membrane, indicating that these findings are fairly common in all kinds of cells. 3) However, the extent of conformational changes in the cell membrane induced by the fixation with KMnO(4), OsO(4) or glutaraldehyde as concluded by Lenard-Singer differs from author's own finding. Regarding this problem it seems to be desirable to study further many other kinds of cells. 4) Noting the resemblance of the CD spectrum of BSA fixed with formaldehyde to that of the cell membrane, the author has assumed that the cell membraneous protein molecules are arranged in the form of aggregation. On the basis of this assumption the author has proposed a modified form of the unit membrane model. This modified unit membrane model has the possibility of being readily transposed to a particulate unit model and it has been designed from the perspective of the circular dichroids as against the dynamic membrane model proposed by Seno. en-copyright= kn-copyright= en-aut-name=ItoNobutaka en-aut-sei=Ito en-aut-mei=Nobutaka kn-aut-name=伊藤信隆 kn-aut-sei=伊藤 kn-aut-mei=信隆 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部病理学教室 END start-ver=1.4 cd-journal=joma no-vol=81 cd-vols= no-issue=5-6 article-no= start-page=385 end-page=393 dt-received= dt-revised= dt-accepted= dt-pub-year=1969 dt-pub=19690630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on soluble proteins of the rats transplanted with Walker carcinoma Part U. The phospholipids in nucleus and mitochondrial fractions of liver, spleen and tumor kn-title=Walker carcinoma移植ラッテ組織中の可溶性蛋白に関する研究 第2編 肝,脾および腫瘍の核ならびにミトコンドリア画分におけるリン脂質について en-subtitle= kn-subtitle= en-abstract= kn-abstract=Phospholipids combined with soluble proteins of the male Wistar Strain rats transplanted with Walker carcinoma were studied. The soluble fractions were extracted by 1) 1/15 M Phosphate Buffer (pH. 7.2), 2) 0.4 M NaCl from the nucleus and mitochondrial fractions of the liver, spleen and tumor of the rat. The phospholipids devided from soluble proteins were analysed and compared with those of normal rat by meaus of photodensitometrical technique and p(32) activity on thin layer chromatogram. 1. Total phospholipid per protein was decreased slightly in liver, increased in spleen of the tumorbearing rat. 2. Sphingomyelin was increased in liver, spleen and tumor tissue, lecithin in spleen and cephalin in tumor tissue were increased slightly. 3. In the tumorous condition, the L/C ratio in liver and spleen was higher than in normal, but in tumor tissue, it was lower than in normal liver or spleen. en-copyright= kn-copyright= en-aut-name=ShinzekiKen en-aut-sei=Shinzeki en-aut-mei=Ken kn-aut-name=新関顕 kn-aut-sei=新関 kn-aut-mei=顕 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部附属病院第一外科教室 END start-ver=1.4 cd-journal=joma no-vol=86 cd-vols= no-issue=3-4 article-no= start-page=117 end-page=125 dt-received= dt-revised= dt-accepted= dt-pub-year=1974 dt-pub=19740430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Comparison of Lipid Metabolism in Whole Blood Cells and Liver Part U. The Effect of Chronic Carbon Tetrachloride Intoxication on Lipid Metabolism kn-title=血液細胞と肝の脂質代謝の比較に関する実験的研究 第2編 慢性四塩化炭素中毒による検討 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In order to investigate the relationships between whole blood cells and liver slices on lipid metabolism in chronic CCl(4) intoxicated rats, the author studied in vitro incorporation of (14)C-acetate Na into gross lipid fracitons, major lipid fractions and total fatty acids. The results obtained are summarized as follows: 1) (14)C incorporation by liver slices into total lipids, unsaponifiable lipids and total fatty acids was markedly increased at 2 weeks, but at 12 weeks it was not so much increased except for total fatty acids than controls. On the other hand, (14)C incorporation by whole blood cells into each of them was similar to that obseved with controls at 2 weeks, while it was slightly decreased at 12 weeks. 2) Not only in acute CCl(4), intoxication but also in the chronic stage, as mentioned in Part I, it is considered that fatty liver would be caused by enhancement of TG and NEFA synthesis in liver, and at the same time lipid metabolism in whole blood cells would contribute to fatty liver. 3) An increae of percent (14)C incorporation by liver slices into fatty acid group 14:0+16:0, namely an increased acitivity of malonyl CoA pathway was observed at 2 weeks as well as at 12 weeks while whole blood cells incorporated relatively more radioactivity into fatty acid group 14:0+16:0 at 2 weeks, but at 12 weeks the percent radioactivity in oleic, 20 carbons' and more longer chains' fatty acids, derived from mitochondrial pathway, showed a significant relative increase. 4) As mentioned in Parts I and U, lipid metabolism in liver slices was influenced strikingly following administration of CCl(4), but that in whole blood cells showed few differences between CCl(4) administered rats and controls. It may be possible to conclude from these results that whole blood cells would contribute to maintain the homeostasis of lipid metabolism in vivo. en-copyright= kn-copyright= en-aut-name=KawauchiMitsuo en-aut-sei=Kawauchi en-aut-mei=Mitsuo kn-aut-name=河内光男 kn-aut-sei=河内 kn-aut-mei=光男 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二内科 END start-ver=1.4 cd-journal=joma no-vol=86 cd-vols= no-issue=3-4 article-no= start-page=107 end-page=115 dt-received= dt-revised= dt-accepted= dt-pub-year=1974 dt-pub=19740430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on Comparison of Lipid Metabolism in Whole Blood Cells and Liver Part I. The Effect of Acute Carbon Tetrachloride Intoxication on Lipid Metabolism kn-title=血液細胞と肝の脂質代謝の比較に関する実験的研究 第1編 急性四塩化炭素中毒による検討 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The present study was designed to investigate some role of whole blood cells in lipid metabolism compared to that of liver in acute carbon tetrachloride intoxicated rats. In order to determine this, in vitro incorporation of (14)C-acetate Na into gross lipid fractions, major lipid fractions and total fatty acids was studied. The experimental animals employed were male Wistar rats, which were subjected to subcutaneous injection of 50% CCl4 in olive oil, 0.2ml/100gm. of body weight. Animals were sacrificed at time intervals of 4 and 48 hours following treatment. The results obtained are summarized as follows: 1) (14)C incorporation by liver slices into total lipids, unsaponifiable lipids and total fatty acids was markedly decreased at 4 hours, but at 48 hours it was strikingly increased in accordance with liver cell regeneration. On the other hand, (14)C incorporation by whole blood cells into each of them showed a trend toward an increase at 4 hours, although there were few differences between carbon tetrachloride administered rats and controls at 48 hours. 2) Percent (14)C incorporation by liver slices into TG and NEFA increased significantly following CCl(4) treatment, while whole blood cells incorporated relatvely more radioactivity into NEFA than that of controls. Consequently it is considered that fatty liver would be caused by enhancement of TG and NEFA synthesis in liver, and at the same time lipid metabolism in whole blood cells would contribute to fatty liver. 3) In acute CCl(4) intoxication of rats, a decrease of percent (14)C incorporation by liver slices into fatty acid group 14:0+16:0, namely the decreased activity of malonyl CoA pathway was observed, while that into 20 carbons and more longer chains, fatty acids, formed via mitochondrial pathway, showed a significant relative increase; the results being similar to those observed with whole blood cells. en-copyright= kn-copyright= en-aut-name=KawauchiMitsuo en-aut-sei=Kawauchi en-aut-mei=Mitsuo kn-aut-name=河内光男 kn-aut-sei=河内 kn-aut-mei=光男 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二内科 END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=5-6 article-no= start-page=345 end-page=354 dt-received= dt-revised= dt-accepted= dt-pub-year=1976 dt-pub=19760630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on lipid metabolism in blood cells Part U. Lipid metabolism in bone marrow cells in vitro kn-title=血液細胞の脂質代謝に関する研究 第一編 phenyl-hydrazine処理家兎血球の脂質代謝(赤血球系細胞を中心に) en-subtitle= kn-subtitle= en-abstract= kn-abstract=The present study was designed to investigate the lipid metabolism in bone marrow and peripheral blood cells. The author studied the in-vitro incorporation of (14)C-acetate Na into gross lipid fraction, major lipid fractions and fatty acids. Results were as follows. 1) The (14)C incorporation into the total lipid was markedly increased in bone marrow cells and whole blood cells of anemic rabbits. On the other hand, in Lanolin induced hyperlipemia, it was significantly decreased than in control, young or old. They were slightly increased but there were no differences among them. 2) After 4 hours' incubation of bone marrow or whole blood cells with (14)C-acetate in vitro, the percentage of the radioactivity recovered in diglyceride and free cholesterol was significantly increased in anemic rabbits, but in hyperlipemia decreased compared with control. 3) In hyperlipimia, the decrease of percent (14)C incorporation by bone marrow cells into fatty acid group 14:0+16:0 was supposed to be derived from the decreased activity of malonyl CoA pathway, while that into 20 Carbon and more longer chain fatty acid, formed via mitochondrial pathway, showed a significant relative increase. On the contrary, in young and old, especially in anemia, the increased activity of malonyl CoA pathway was observed in bone marrow cells but the decreased of mitochondrial pathway; the same result was obtained in peripheral whole blood cells, too. en-copyright= kn-copyright= en-aut-name=ShimizuYoshito en-aut-sei=Shimizu en-aut-mei=Yoshito kn-aut-name=清水能人 kn-aut-sei=清水 kn-aut-mei=能人 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二内科 END start-ver=1.4 cd-journal=joma no-vol=88 cd-vols= no-issue=3-4 article-no= start-page=197 end-page=207 dt-received= dt-revised= dt-accepted= dt-pub-year=1976 dt-pub=19760430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on the lipid peroxidation in mitochondria of x-ray whole-body irradiated rat liver U. Changes of fatty acid composition and ferrous ion-induced peroxidation of mitochondrial lipid after whole-body irradiation kn-title=X線全身照射のラット肝ミトコンドリアにおける脂質過酸化反応に関する研究 第二編 脂質ならびに脂肪酸組成の変動と抽出脂質のFe(++)誘導脂質過酸化反応について en-subtitle= kn-subtitle= en-abstract= kn-abstract=Ferrous ion-induced lipid peroxidation of the mitochondria isolated from rat liver on the 3rd day after x-ray whole-body irradiation at 650R showed shortening of the lag of induction period and more acceleration of the activity than those of normal mitochondria (Part 1). Further investigations were made on the mitochondria on the 3rd day after irradiation at 650R in regard to fatty acid compositions and Fe(++) -induced peroxidation of total or fractionated mitochondrial lipids. The results are represented as follows. 1) Fatty acid composition of the mitochondria after lipid peroxidation showed the decrease of polyenoic acids (C-20:4, C-22:6), suggesting the polyenoic acids are substrate of the reaction. 2) Changes of fatty acid composition of mitochondria after whole-body irradiation at 650R were shown decreasing of unsaturated fatty acid due to the decrement of C-18:1 and C-18:2, but the component of polyenoic acid increased relatively. These changes are transient, reaching a maximum on the 3rd day after irradiation, and this tendency is parallel to that of lipid peroxidation activity of the mitochondria whole-body irradiated. 3) No difference of the rate of peroxidation observed between total lipids extracted from normal and from whole-body irradiated mitochondria, and the lag of induction period was not seen in both reactions. 4) Peroxidation of the total lipid was seen markedly in the phospholipid fraction and slightly in the simple lipid fractions. Effect of whole-body irradiation on the peroxidation activities of the phospholipid was not observed significantly, despite of the difference seen in their fatty acid compositions. 5) Peroxidation of subfractionated phospholipid by a thin-layer chromatography showed marked activity in the fractions of lecithin and aminophosphatide containing large amounts of C-20:4 and C-22:6: Recovery of the activity of the subfractions increased markedly comparing to the total phospholipid, and effect of whole-body irradiation appeared significantly in these subfractions. However, relationship between activities of the peroxidation and fatty acid compositions of the subfractions cannot seen. It is suggested the mutual interaction of phopholipid subfractions on the peroxidation to decrease the activity, and some of lipid became more sensitive to peroxidation by irradiation. 6) Relative amount of phospholipid to total lipid increased in whole-body irradiated samples. 7) From these findings, it was discussed that the acceleration of Fe(++) -induced lipid peroxidation in mitochondrial level is due to the change of fatty acid composition and association of lipid in the membrane. en-copyright= kn-copyright= en-aut-name=WakabayashiHiroshi en-aut-sei=Wakabayashi en-aut-mei=Hiroshi kn-aut-name=若林弘 kn-aut-sei=若林 kn-aut-mei=弘 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部放射線医学教室 END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=11-12 article-no= start-page=1491 end-page=1495 dt-received= dt-revised= dt-accepted= dt-pub-year=1978 dt-pub=19781230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effects of nitrosamines on the mitochondrial membrane kn-title=ニトロソアミンのミトコシドリア膜に対する作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In order to clarify the biological toxities of nitrosamines, the effects of nitrosamines on the biological membrane, especially on the energy transfer reaction and on the K(+) compartmentation of mitochondria were examined. The results obtained were as follows; 1) DPNA and DBNA uncoupled the oxidative phosphorylation of rat liver mitochondria at the low concentration (about 0.2 mM solution). 2) Uncoupling activities of DPNA and DBNA to the mitochondrial oxidative phosphorylation were increased in accordance with the increase in concentration and showed a remarkable increase within the concentration range from 0.1 mM to 0.2 mM solution. 3) The release of K(+) from mitochondria was induced by treatment with DPNA or DBNA, especially was accelerated by DPNA. However, it could not be induced by treatment of 1mM DMNA or DENA. 4) The order of K(+) -release intensity induced by nitrosamines was corresponding to that of uncoupling activities of nitrosamines. 5) In conclusion, it was recognized that the functions of mitochondrial membrane were damaged by nitrosamines and their injurious effects were influenced by their chemical structures in the order of DPNA, DBNA, DENA and DMNA. This suggests that nitrosamines may have injurious effects on the function of the biological membrane, as well as their already recognized effects of carcinogenecity or liver injury (liver cirrhosis). en-copyright= kn-copyright= en-aut-name=IshiiKunihiko en-aut-sei=Ishii en-aut-mei=Kunihiko kn-aut-name=石井邦彦 kn-aut-sei=石井 kn-aut-mei=邦彦 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=9-10 article-no= start-page=1297 end-page=1308 dt-received= dt-revised= dt-accepted= dt-pub-year=1978 dt-pub=19781030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Participation of superoxide generating system, superoxide dismutase and vitamin E in the radiation hazards kn-title=放射線障害におけるスーパーオキサイド生成系(O(2))とスーパーオキサイド・ディスムターゼ(SOD)及びビタミンEの関与に対する考察 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In relation to the mechanism by which hemolysis was induced in radiated human erythrocytes in vitro, several inducements of membrane lipid peroxidation and protective effects of V.E and SOD were investigated. Results obtained were as follows: (1) K(+)-release from erythrocytes was accelerated by radiation prior to hemolysis. These accelerated hemolysis and K(+)-release were protected remarkably by V.E and evidently by SOD. (2) Mitochondrial Fe(2+) induced and Fe(3+)-O(2) generating system -ADP induced lipid peroxidation, and microsomal O(2) generating system -induced lipid peroxidation were also protected by V.E and SOD. (3) Radiation of X-ray or (60)Co γ-ray accelerated lipid peroxidation of liver homogenate, microsome and liposome. Some of these accelerated lipid peroxidations were protected effectively by V.E and SOD. These results suggest that O(2) and/or OH. generation by radiation induces of membrane lipid peroxidation, which leads deterioration of membrane resulting in the change of ion permeability and then hemolysis. en-copyright= kn-copyright= en-aut-name=AonoKaname en-aut-sei=Aono en-aut-mei=Kaname kn-aut-name=青野要 kn-aut-sei=青野 kn-aut-mei=要 aut-affil-num=1 ORCID= en-aut-name=YamamotoMichio en-aut-sei=Yamamoto en-aut-mei=Michio kn-aut-name=山本道夫 kn-aut-sei=山本 kn-aut-mei=道夫 aut-affil-num=2 ORCID= en-aut-name=IidaSosuke en-aut-sei=Iida en-aut-mei=Sosuke kn-aut-name=飯田荘介 kn-aut-sei=飯田 kn-aut-mei=荘介 aut-affil-num=3 ORCID= en-aut-name=UtsumiKozo en-aut-sei=Utsumi en-aut-mei=Kozo kn-aut-name=内海耕慥 kn-aut-sei=内海 kn-aut-mei=耕慥 aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部附属病院中央放射線部 affil-num=2 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=3 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=4 en-affil= kn-affil=岡山大学医学部癌源研究所生化学部門 END start-ver=1.4 cd-journal=joma no-vol=87 cd-vols= no-issue=3-4 article-no= start-page=279 end-page=288 dt-received= dt-revised= dt-accepted= dt-pub-year=1975 dt-pub=19750430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Changes of Mitochondrial Function by CCl(4) kn-title=四塩化炭素中毒ラットの肝ミトコンドリア機能の変動について en-subtitle= kn-subtitle= en-abstract= kn-abstract=It has been reported that the liver intoxication by CCl(4) is primarily caused from damages in mitochondrial functions. The present systematic investigation revealed some changes in mitochondrial functions, and the results are presented as follows. With mitochondria isolated from the liver of rat with CCl(4) intoxication an investigation was carried out on changes of the energy metabolism on the lipid peroxidation which is thought to have an important bearing on the onset of liver damages, as well as on changes of related substances. Simultaneously, changes in mitochondria isolated from normal rat liver were studied in vitro in the presence of CCl(4). For the intoxication group the mixture of 0.4ml CCl(4) and 1.6ml salad oil was injected into the rat peritoneal cavity and the liver was taken out of the animal 16 hours later when CCl(4)-intoxication was most marked, and mitochondria were isolated to be used for the experiment. For the control group 2.0ml salad oil alone was injected intraperitoneally, and mitochondria isolated from the liver taken out 16 hours later were used. In the in vitro experiment the mitochondria isolated from normal rat liver served for this purpose. The results may briefly summarized as follows: 1) In the CCl(4)-intoxicated liver the dehydrogenase system of mitochondria is most markedly damaged. 2) The energy conversion system is so damaged that the ATP synthesis is markedly decreased. 3) Ion-transport system which acts synergistically with the energy conversion of early stage is damaged. 4) The lipid peroxidation induced by Fe(2+) is markedly diminished. 5) The phospholipid content of mitochondria and arachidoic acid content of phospholipid are decreased, while the content of tryglyceride is increased. 6) CCl(4) acts on the oxidative phosphrylation of the normal rat liver counter-synergistically, though only weakly. 7) When CCl(4) is added to normal rat liver in vitro, the lipid peroxidation is enhanced, on the contrary to the situation of CCl(4)-intoxicated rat liver. These findings suggest that the onset mechanisms of mitochonrial functional disturbances may be explained as due to the damage to the mitochondrial membrane, the damage to the membrane system and energy metabolic system brought about by CCl(4) as well as by the by-products of membrane disintegration. en-copyright= kn-copyright= en-aut-name=AkahoriFumihiko en-aut-sei=Akahori en-aut-mei=Fumihiko kn-aut-name=赤堀文彦 kn-aut-sei=赤堀 kn-aut-mei=文彦 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第1病理学教室 END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=5-6 article-no= start-page=689 end-page=695 dt-received= dt-revised= dt-accepted= dt-pub-year=1978 dt-pub=19780630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The mutual effects of N0(2) + Cd(2+) and N0(2) + Zn(2+) on the mitochondrial membrane. kn-title=ミトコンドリア膜に対する亜硝酸イオンとカドミウムイオン,亜鉛イオンの相互作用について en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mutual effects of NaNO(2) + CdCl(2) and NaNO(2) + ZnCl(2) on the oxidative phosphorylation of rat liver mitochondria were examined and following results were obtained. (1) Mixed solution of NaNO(2) and CdCl(2) more decreases respiratory control index at any concentration of NaNO(2) (0-8.6mM) than the index without addition of 4.3μM CdCl(2) respectively. (2) Mixed sollution of CdCl(2) and NaNO(2) more decreases respiratory control index at any concentration of CdCl(2) (0-10μM) than the index without addition of 5mM NaNO(2) respectively. (3) Mixed sollution of NaNO(2) and ZnCl(2) more decreases relative activity of State-3 and dinitrophenol stimulated respiration at any concentration of NaNO(2) (0-8.6mM) than the activity without addition of 4.3μM ZnCl(2) respectively. (4) Mixed sollution of ZnCl(2) and NaNO(2) more decreases relative activity of State-3 and dinitrophenol stimulated respiration at any concentration of ZnCl(2) (0-10μM) than the activity without addition of 5mM NaNO(2) respectively. en-copyright= kn-copyright= en-aut-name=InoueKentaro en-aut-sei=Inoue en-aut-mei=Kentaro kn-aut-name=井上堅太郎 kn-aut-sei=井上 kn-aut-mei=堅太郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=87 cd-vols= no-issue=1-2 article-no= start-page=95 end-page=104 dt-received= dt-revised= dt-accepted= dt-pub-year=1975 dt-pub=19750228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on the Lipid Metabolism in Platelets Part I Studies on the Lipid Metabolism in Platelets from Arteriosclerotic, Hyperlipidemic Patients and Diabetics kn-title=血小板による脂質代謝の研究 第1篇 動脈硬化症,高脂血症及び糖尿病患者の血小板について en-subtitle= kn-subtitle= en-abstract= kn-abstract=The author studied on the in vitro incorporation of I-(14)C-acetate into total lipids and total fatty acids of platelets. The results are summarized as follows. I. The pattern of incorporation of radioactivity into fatty acids of platelets obtained from normal subjects. a. It was ascertained that Platelets synthesized lipids, particularly fatty acids and fatty acid synthesis was considered to be via both mitochondrial and malonyl CoA pathways in platelets. b. Platelets showed usually a significant decrease in percent (14)C incorporation into oleic acid from I-(14)C-acetate as compared with liver, adipose tissue and leucocytes. c. Platelets showed an increase in percent (14)C incorporation into nonesterified fatty acid and a decrease into triglyceride as compared with liver, adipose and leucocytes. d. Every fatty acid synthesized by platelets was selectively esterified to phospholipid and triglyceride. e. The percentage of radioactive oleic acid in triglyceride fatty acids was more increased than that in nonesterified fatty acids. 2. The pattern of incorporation of radioactivity into fatty acids of platelets obtained from patients with arteriosclerosis, hyperlipidemia and diabetes mellitus. a. The (14)C incorporation into total fatty acid was increased markedly in patients of hyperlipidemia and obesity. b. The (14)C incorporation into cholesterol also was increased in these patients. c. Fatty acid synthesis via malonyl CoA pathway was decreased and alternatively fatty acid synthesis was increased via mitochondrial pathway. d. Increased (14)C incorporation into oleic acid was observed and considered to be due to the enhancement of monounsaturation of stearic acid. en-copyright= kn-copyright= en-aut-name=MizukawaShiro en-aut-sei=Mizukawa en-aut-mei=Shiro kn-aut-name=水川士郎 kn-aut-sei=水川 kn-aut-mei=士郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二内科 END start-ver=1.4 cd-journal=joma no-vol=89 cd-vols= no-issue=11-12 article-no= start-page=1507 end-page=1510 dt-received= dt-revised= dt-accepted= dt-pub-year=1977 dt-pub=19771230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The effects of ruthenium red on the K(+) release of mitochondria induced by Cd(2+) and on the binding of Cd(2+) with mitochondrial membrane kn-title=環境汚染物質(重金属など)の生体膜に対する作用 第4報 カドミウムによるミトコンドリアのK(+)遊出作用及びカドミウムのミトコンドリア膜への結合に対するルテニウムレッドの作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effects'of ruthenium red (RR) on the K(+) release induced by Cd(2+) and on the binding of Cd(2+) with mitochondrial membrane were examined and the following results were obtained. 1) The K(+) release of mitochondria induced by Cd(2+) was inhibited by the compounds which had the affinity to the Ca(2+)-binding site, in the order of RR, procaine. 2) Binding of Cd(2+) with mitochondrial membrane was inhibited by RR. en-copyright= kn-copyright= en-aut-name=HasegawaTohoru en-aut-sei=Hasegawa en-aut-mei=Tohoru kn-aut-name=長谷川亨 kn-aut-sei=長谷川 kn-aut-mei=亨 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=89 cd-vols= no-issue=11-12 article-no= start-page=1501 end-page=1505 dt-received= dt-revised= dt-accepted= dt-pub-year=1977 dt-pub=19771230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The mutual effects of Cd(2+) and ruthenium red on rat liver mitochondrial energy transfer reaction kn-title=環境汚染物質(重金属など)の生体膜に対する作用 第3報 カドミウムとルテニウムレッドの相互作用,特にミトコンドリアの酸化的リン酸化反応に対して en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mutual effects of Cd(2+) and ruthenium red on rat liver mitochondrial energy transfer reaction are described. In results, ruthenium red recovered the depression of the oxidative phosphorylation induced by Cd(2+). Ruthenium red suppressed the K(+) release induced by Cd(2+). As the binding site of the Cd(2+) have other than the binding site of ruthenium red, the site of ruthenium red is greatly related with the inhibitory effect of Cd(2+) and this site is similar to the binding site of Ca(2+). en-copyright= kn-copyright= en-aut-name=HasegawaTohoru en-aut-sei=Hasegawa en-aut-mei=Tohoru kn-aut-name=長谷川亨 kn-aut-sei=長谷川 kn-aut-mei=亨 aut-affil-num=1 ORCID= en-aut-name=NogamiYusaku en-aut-sei=Nogami en-aut-mei=Yusaku kn-aut-name=野上裕作 kn-aut-sei=野上 kn-aut-mei=裕作 aut-affil-num=2 ORCID= en-aut-name=OgataMasana en-aut-sei=Ogata en-aut-mei=Masana kn-aut-name=緒方正名 kn-aut-sei=緒方 kn-aut-mei=正名 aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 affil-num=2 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 affil-num=3 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=89 cd-vols= no-issue=11-12 article-no= start-page=1495 end-page=1500 dt-received= dt-revised= dt-accepted= dt-pub-year=1977 dt-pub=19771230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The effects of organic mercury compounds on the biomembrane with specific reference to the K(+) compartment kn-title=環境汚染物質(重金属など)の生体膜に対する作用 第2報 各種有機水銀の生体膜に対する作用,特にK(+)区画性に対して en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effects of organic mercury compounds on the biomembrane were studied with specific reference to the K(+) compartment and the following results were obtained. 1) PhMC, PhMA, and MMC had effects of decoupling action on the oxidative phosphorylation, and PCMB inhibited the ADP-stimulated respiration, and mercury chloride inhibited the respiration. 2) On the red blood cell and mitochondrial membrane, these organic mercury compounds induced the K(+) release in the order of HgCl(2) PhMC PhMA MMC PCMB. 4) It is suggested that the liophilic nature of organic mercury compounds plays an important role in the reaction of K(+) release. en-copyright= kn-copyright= en-aut-name=HasegawaTohoru en-aut-sei=Hasegawa en-aut-mei=Tohoru kn-aut-name=長谷川亨 kn-aut-sei=長谷川 kn-aut-mei=亨 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=89 cd-vols= no-issue=11-12 article-no= start-page=1487 end-page=1494 dt-received= dt-revised= dt-accepted= dt-pub-year=1977 dt-pub=19771230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The effects of various heavy metal ions (such as Hg(2+), Cd(2+), Cu(2+) and Zn(2+)) on mitochondrial membrane with specific reference to K(+) compart mentation kn-title=環境汚物(重金属など)の生体膜に対する作用 第1報 各種重金属イオンのミトコンドリア膜に対する作用,特にK(+)区画性について en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effects of various heavy metal ions such as Hg(2+), Cd(2+), Cu(2+) and Zn(2+) on mitochondrial membrane were investigated and the following results were obtained; 1) Hg(2+), Cd(2+), Cu(2+) and Zn(2+) released the potassium ion from the mitochondria with the increasing level of an affinity to SH compounds. 2) The release of K(+) by Cd(2+) and Zn(2+) was inhibited in the presence of Mg(2+), but the release of K(+) by Hg(2+) and Cu(2+) was not affected. 3) In the presence of ImM DTT, the release of K(+) by all of these metal ions was completely inhibited.4) The K+ release by Hg(2+) and Cu(2+) was inhibited by DTNB or PCMB which bound prefencially the thiol component of membrane protein, but the release by Cd(2+) and Zn(2+) was not inhibited by these reagents. 5) The release of K(+) decoupled the oxidative phosphorylation by treatment of the heavy metal ions. en-copyright= kn-copyright= en-aut-name=HasegawaTohoru en-aut-sei=Hasegawa en-aut-mei=Tohoru kn-aut-name=長谷川亨 kn-aut-sei=長谷川 kn-aut-mei=亨 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=3-4 article-no= start-page=257 end-page=263 dt-received= dt-revised= dt-accepted= dt-pub-year=1978 dt-pub=19780430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effects of sodium nitrite (NaNO(2)) and sodium nitrate (NaNO(3)) on the mitochondrial membrane kn-title=亜硝酸イオンと硝酸イオンのミトコンドリア膜に対する作用について en-subtitle= kn-subtitle= en-abstract= kn-abstract=Effects of NaNO(2) and NaNO(3) on the oxidative phosphorylation of mitochondria were studied, and following results were obtained. 1) The effect of NaNO(2) on the oxidative phosphorylation is higher than NaNO(3). 2) Relative activity of State 4 is activated by NaNO(2) (1-10mM) added to reaction mixture. 3) The respiratory control index of mitochondria is decreased by NaNO(2). 4) The effect of NO(2) on oxidative phosphorylation in the borate buffer as reaction mixture is higher than that in the tris-HCL buffer. It is suggested that NO(2) has a probability of the reaction on -NH(2) site of mitochondria. en-copyright= kn-copyright= en-aut-name=InoueKentaro en-aut-sei=Inoue en-aut-mei=Kentaro kn-aut-name=井上堅太郎 kn-aut-sei=井上 kn-aut-mei=堅太郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=1-2 article-no= start-page=251 end-page=256 dt-received= dt-revised= dt-accepted= dt-pub-year=1978 dt-pub=19780228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The mutual effects of Cd(2+), ruthenium red and Ca(2+) on the mitochondrial latent ATPase activity kn-title=ミトコンドリアのATPase活性に対するカドミウム,ルテニウムレッド及びカルシウムの相互作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mutual effects of Cd(2+), ruthenium red and Cd(2+) on the rat liver mitochondrial latent ATPase activity were studied and the following results were obtained. (1) The mitochondrial latent ATPase activity was stimulated by Cd(2+), and higher concentration of Cd(2+) added to the reaction mixture showed higher ATPase activity. (2) The ATPase activity induced by Cd(2+) was inhibited by ruthenium red, having the high affinity for the Ca(2+) -binding site of mitochondria. (3) The ATPase activity induced by Cd(2+) was also inhibited by Ca(2+). (4) In conclusion, the site of mitochondria, on which Cd(2+) activates latent ATPase, will be related with the Ca(2+) -binding site of mitochondria. en-copyright= kn-copyright= en-aut-name=KenmotsuKatashi en-aut-sei=Kenmotsu en-aut-mei=Katashi kn-aut-name=劒持堅志 kn-aut-sei=劒持 kn-aut-mei=堅志 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=1-2 article-no= start-page=173 end-page=178 dt-received= dt-revised= dt-accepted= dt-pub-year=1978 dt-pub=19780228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The effects of benzothiophene and dibenzothiophene on the mitochondrial membrane kn-title=ベンヅチオフェン,ジベンゾチオフェンのミトコンドリア膜に対する作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effects of benzothiophene and dibensothiophene on the mitochondrial membrane were studied and the following results were obtained. 1. The uncoupling actions of benzothiophene and dibenzothiophene on the energy transfer reaction of mitochondria were observed in the order of dibenzothiophene and benzothiophene. 2. The K(+) release was induced by benzothiophene and dibenzothiophene, and its ability of K(+) release was in the order of dibenzothiophene and benzothiophene. 3. The uncoupling actions of naphthalane and anthracene were similar to that of benzothiophene and dibenzothiophene respectively. en-copyright= kn-copyright= en-aut-name=HasegawaTohoru en-aut-sei=Hasegawa en-aut-mei=Tohoru kn-aut-name=長谷川亨 kn-aut-sei=長谷川 kn-aut-mei=亨 aut-affil-num=1 ORCID= en-aut-name=OgataMasana en-aut-sei=Ogata en-aut-mei=Masana kn-aut-name=緒方正名 kn-aut-sei=緒方 kn-aut-mei=正名 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 affil-num=2 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=90 cd-vols= no-issue=1-2 article-no= start-page=167 end-page=171 dt-received= dt-revised= dt-accepted= dt-pub-year=1978 dt-pub=19780228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The effect of sodium nitrite on the mitochondrial latent ATPase activity kn-title=亜硝酸ナトリウムのミトコンドリアATPase活性化作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effect of sodium nitrite on the mitochondrial latent ATPase activity was studied and the following results were obtained. 1. Sodium nitrite stimulated the latent ATPase activity, and its stimulating activity was dependent on its concentration added to the reaction mixture. 2. The activity of the ATPase stimulated by sodium nitrite was lower in the tris buffer having the amino group than that in the borate buffer. 3. The ability of sodium nitrite on release respiratory control was lower in the high concentration of mitochondrial protein than that in the low concentration of protein. en-copyright= kn-copyright= en-aut-name=HasegawaTohoru en-aut-sei=Hasegawa en-aut-mei=Tohoru kn-aut-name=長谷川亨 kn-aut-sei=長谷川 kn-aut-mei=亨 aut-affil-num=1 ORCID= en-aut-name=OgataMasana en-aut-sei=Ogata en-aut-mei=Masana kn-aut-name=緒方正名 kn-aut-sei=緒方 kn-aut-mei=正名 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 affil-num=2 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 END start-ver=1.4 cd-journal=joma no-vol=92 cd-vols= no-issue=11-12 article-no= start-page=1085 end-page=1089 dt-received= dt-revised= dt-accepted= dt-pub-year=1980 dt-pub=19801230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The effect of chlorinated mono aromatic hydrocarbons on biological membranes (1. The effect of various concentrations of chlorinated mono aromatic hydrocarbons on normal isolated rat liver mitochondrial oxidative phosphorylation) kn-title=ベンゼン塩素化合物の生体膜に対する作用 第1報 分離正常ラット肝ミトコンドリアに於ける各化合物の各種濃度の酸化的リン酸化反応に対する影響 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effect of mono-, di-, tri-, and tetra-chlorinated benzene on mitochondrial oxidative phosphorylation was determined and the following results were obtained. 1) Chlorinated mono-aromatic hydrocarbons inhibited respiratory control strongly by increasing state 4 respiration and decreasing state 3 respiration. 2) Lower concentrations of mitochondrial protein showed higher inhibitory effects for 1,2,3-tichloro benzene on respiratory control. 3) The respiratory control index decreased with increase in the number of chlorine. 4) The respiratory control index decreased with increase in the concentration of chlorinated benzene. 5) Decrease in respiratory control index was in the order of orth>meta>para-dichloro benzenes. There were differences between the isomers. en-copyright= kn-copyright= en-aut-name=MoriTakaaki en-aut-sei=Mori en-aut-mei=Takaaki kn-aut-name=森孝昭 kn-aut-sei=森 kn-aut-mei=孝昭 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生 en-keyword=肝臓 kn-keyword=肝臓 en-keyword=ベンゼン塩素化合物 kn-keyword=ベンゼン塩素化合物 en-keyword=ミトコンドリア kn-keyword=ミトコンドリア en-keyword=酸化的リン酸化反応 kn-keyword=酸化的リン酸化反応 en-keyword=生体膜 kn-keyword=生体膜 END start-ver=1.4 cd-journal=joma no-vol=92 cd-vols= no-issue=9-10 article-no= start-page=1015 end-page=1024 dt-received= dt-revised= dt-accepted= dt-pub-year=1980 dt-pub=19801030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Alteration of mitochondrial functions by lipid peroxidation and inhibition by biscoclaurine alkaloid kn-title=脂質過酸化反応によるミトコンドリァ機能の変化とビスコクラウリン型アルカロイドによる阻害作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=During investigation of the changes in mitochondrial function accompanying lipid peroxidation, it was found that a biscoclaurine alkaroid protected their functional changes. The results obtained were as follows: 1) Fe(2+) induces lipid peroxidation of isolated mitochondria, resulting in deterioration of oxidative phosphorylation. 2) This deterioration relates to alteration in ion compartmentation of the mitochondrial membrane and an increase in latent ATPase activity. 3) This deterioration by Fe(2+) in ion compartmentation of mitochondrial membrane is strongly protected by a biscoclaurine alkaloid, cepharanthine. 4) Cepharanthine also inhibits the mitochondrial. lipid peroxidation induced by Fe(2+). 5) The protective effect of cepharanthine against deterioration in mitochondrial functions caused by Fe(2+) depends on its inhibitive action on lipid peroxidation as well as on its membrane stabilizing action. 6) Cepharanthine inhibits the lipid peroxidation of soybean lecithine liposomes by (60)Co-irradiation. 7) The action of cepharanthine described above is common to head to head type of biscoclaurin alkaloids which have diether bonds. en-copyright= kn-copyright= en-aut-name=AonoKaname en-aut-sei=Aono en-aut-mei=Kaname kn-aut-name=青野要 kn-aut-sei=青野 kn-aut-mei=要 aut-affil-num=1 ORCID= en-aut-name=MorimotoSetsuo en-aut-sei=Morimoto en-aut-mei=Setsuo kn-aut-name=森本節夫 kn-aut-sei=森本 kn-aut-mei=節夫 aut-affil-num=2 ORCID= en-aut-name=HashimotoKeiji en-aut-sei=Hashimoto en-aut-mei=Keiji kn-aut-name=橋本啓二 kn-aut-sei=橋本 kn-aut-mei=啓二 aut-affil-num=3 ORCID= en-aut-name=SatoKatashi en-aut-sei=Sato en-aut-mei=Katashi kn-aut-name=佐藤功 kn-aut-sei=佐藤 kn-aut-mei=功 aut-affil-num=4 ORCID= en-aut-name=JojaIkuo en-aut-sei=Joja en-aut-mei=Ikuo kn-aut-name=上者郁夫 kn-aut-sei=上者 kn-aut-mei=郁夫 aut-affil-num=5 ORCID= en-aut-name=KimotoShin en-aut-sei=Kimoto en-aut-mei=Shin kn-aut-name=木本真 kn-aut-sei=木本 kn-aut-mei=真 aut-affil-num=6 ORCID= en-aut-name=EzoeHiroshi en-aut-sei=Ezoe en-aut-mei=Hiroshi kn-aut-name=江添弘 kn-aut-sei=江添 kn-aut-mei=弘 aut-affil-num=7 ORCID= en-aut-name=TakedaYoshihiro en-aut-sei=Takeda en-aut-mei=Yoshihiro kn-aut-name=竹田芳弘 kn-aut-sei=竹田 kn-aut-mei=芳弘 aut-affil-num=8 ORCID= en-aut-name=MiyakeMasayoshi en-aut-sei=Miyake en-aut-mei=Masayoshi kn-aut-name=三宅正淑 kn-aut-sei=三宅 kn-aut-mei=正淑 aut-affil-num=9 ORCID= en-aut-name=HayashiHidehiro en-aut-sei=Hayashi en-aut-mei=Hidehiro kn-aut-name=林英博 kn-aut-sei=林 kn-aut-mei=英博 aut-affil-num=10 ORCID= en-aut-name=WakabayashiHisao en-aut-sei=Wakabayashi en-aut-mei=Hisao kn-aut-name=若林寿生 kn-aut-sei=若林 kn-aut-mei=寿生 aut-affil-num=11 ORCID= en-aut-name=TamaiToyosato en-aut-sei=Tamai en-aut-mei=Toyosato kn-aut-name=玉井豊理 kn-aut-sei=玉井 kn-aut-mei=豊理 aut-affil-num=12 ORCID= en-aut-name=MorinoYasuo en-aut-sei=Morino en-aut-mei=Yasuo kn-aut-name=森野靖雄 kn-aut-sei=森野 kn-aut-mei=靖雄 aut-affil-num=13 ORCID= en-aut-name=ShiraishiNoriyuki en-aut-sei=Shiraishi en-aut-mei=Noriyuki kn-aut-name=白石則之 kn-aut-sei=白石 kn-aut-mei=則之 aut-affil-num=14 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部附属病院中央放射線部 affil-num=2 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=3 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=4 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=5 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=6 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=7 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=8 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=9 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=10 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=11 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=12 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=13 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=14 en-affil= kn-affil=高知医科大学生物学教室 en-keyword=Lipid Peroxidation kn-keyword=Lipid Peroxidation en-keyword=Cepharanthine (Biscoclaurine Alkaloid) kn-keyword=Cepharanthine (Biscoclaurine Alkaloid) en-keyword=Mitochondrial Function kn-keyword=Mitochondrial Function END start-ver=1.4 cd-journal=joma no-vol=92 cd-vols= no-issue=3-4 article-no= start-page=329 end-page=340 dt-received= dt-revised= dt-accepted= dt-pub-year=1980 dt-pub=19800430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Anticytoplasmic antibodies in systemic lupus erythematosus kn-title=全身性エリテマトーデスにおける抗細胞質抗体の検索 (蛍光抗体法を中心として) en-subtitle= kn-subtitle= en-abstract= kn-abstract=By the indirect fluorescent antibody technique, sera of patients with systemic lupus erythematosus were used to stain the cytoplasm of proximal tubule cells of rat kidney frozer sections and the cytoplasm of cells in frozen sections of rat liver. Since the cytoplasmic stainings of rat liver were absorbed with ribosomes and the stainings of proximal tubules were absorbed with mitochondria, the sera were thought to contain either anit-ribosomal antibodies or anti-mitochondrial antibodies. By Ouchterlony methods, some sera produced precipitin lines against 105,000 G supernatant of rat liver homogenate distinct from the ribosomal system. This antigen activity was present in the first peak of a Sephadex G-100 column chromatograph. en-copyright= kn-copyright= en-aut-name=MurakamiMikio en-aut-sei=Murakami en-aut-mei=Mikio kn-aut-name=村上幹郎 kn-aut-sei=村上 kn-aut-mei=幹郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学第三内科 en-keyword=全身性エリテマトーデス(SLE) kn-keyword=全身性エリテマトーデス(SLE) en-keyword=抗細胞質抗体 kn-keyword=抗細胞質抗体 en-keyword=抗ミトコンドリア抗体 kn-keyword=抗ミトコンドリア抗体 en-keyword=抗リボゾーム抗体 kn-keyword=抗リボゾーム抗体 en-keyword=105,000G上清成分 kn-keyword=105,000G上清成分 END start-ver=1.4 cd-journal=joma no-vol=91 cd-vols= no-issue=11-12 article-no= start-page=1455 end-page=1460 dt-received= dt-revised= dt-accepted= dt-pub-year=1979 dt-pub=19791230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Experimental study of Polychlorinated naphthalene (PCN) intoxication 1. Effect of PCNs on oxidative phosphorylation of rat liver mitochondriain a test tube kn-title=ポリ塩化ナフタリン(PCN)中毒に関する実験的研究 第1報 PCNの正常ラツト肝ミトコンドリアの酸化的リン酸化に対する作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Effect of PCNs on normal isolated mitochondrial membrane was studied and the results obtained were as follows. 1) PCNs inhibited the state 3 respiration, and stimulated the state 4 respiration (namely uncoupling action). 2) The proportional relationship between a decrease in RCI and an increase in concentration of Halowax 1001 (PCN) was recognized, and a decrease tendency of ADP/O ratio was observed within the range of PCN concentration measured. 3) PCNs induced a K(+) release in mitochondria and the release effect was the strongest in Halowax 1031 (PCN). 4) Discussion was made that effects of PCNs on the mitochondrial membrane were seemed to be related to their complex characters which are the content of chlorine and their isomers. en-copyright= kn-copyright= en-aut-name=OhgumaKatsuaki en-aut-sei=Ohguma en-aut-mei=Katsuaki kn-aut-name=大熊勝明 kn-aut-sei=大熊 kn-aut-mei=勝明 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生 en-keyword=ポリ塩化ナフタリン kn-keyword=ポリ塩化ナフタリン en-keyword=酸化的リン酸化 kn-keyword=酸化的リン酸化 en-keyword=呼吸活性 kn-keyword=呼吸活性 en-keyword=K(+)遊出 kn-keyword=K(+)遊出 END start-ver=1.4 cd-journal=joma no-vol=91 cd-vols= no-issue=11-12 article-no= start-page=1447 end-page=1454 dt-received= dt-revised= dt-accepted= dt-pub-year=1979 dt-pub=19791230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Oxidative phosphorylation of rat liver and kidney mitochondria after Cd intoxication and the preventive effect of Mg kn-title=環境汚染物質(重金属など)の生体膜に対する作用 第5報 Cd投与ラットにおける肝,腎ミトコンドリアの酸化的リン酸化反応及びMg投与の影響 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Experimental acute intoxication from cadmium chloride in the rat was studied with specific reference to change in the activity of mitochondrial oxidative phosphorylation in the liver and kidney. Various concentrations of cadmium chloride (2.5, 5.0, 10.0 mg/Kg) were given by intraperitoneal injection. Two hours after cadmium injection, the activity of liver and kidney mitochondrial oxidative phosphorylation had decreased, suggesting that cadmium uncoupled oxidative phosphorylation in liver and kidney mitochondria. A dose response relationship of cadmium uncoupling was observed in liver mitochondria, but was not observed in kidney mitochondria indicating that kidney mitochondria were more sensitive to cadmium than liver mitochondria were. A single injection of 250 mg/Kg of magnesium chloride prevented the uncoupling action of cadmium in liver mitochondria but not in kidney mitochondria. Magnesium did not prevent the uncoupling action of mercury chloride in liver or kidney mitochondria. The preventive action of magnesium chloride was evident in in vitro liver mitochondria but not in in vitro kidney mitochondria. The effect of magnesium on cadmium action was discussed. en-copyright= kn-copyright= en-aut-name=HasegawaTohoru en-aut-sei=Hasegawa en-aut-mei=Tohoru kn-aut-name=長谷川亨 kn-aut-sei=長谷川 kn-aut-mei=亨 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 en-keyword=カドミウム kn-keyword=カドミウム en-keyword=肝及び腎ミトコンドリア kn-keyword=肝及び腎ミトコンドリア en-keyword=酸化的リン酸化 kn-keyword=酸化的リン酸化 en-keyword=マグネシウム kn-keyword=マグネシウム END start-ver=1.4 cd-journal=joma no-vol=94 cd-vols= no-issue=11-12 article-no= start-page=1045 end-page=1050 dt-received= dt-revised= dt-accepted= dt-pub-year=1982 dt-pub=19821230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on the biological toxicity of several hydrocarbon pollutants of the environment Report 2. The effect of halogenated hydrocarbons on oxidative phosphorylation and potassium compartmentalization of rat liver mitochondria. kn-title=環境汚染物質(炭化水素)の生態系への影響 第2報 ラット肝ミトコンドリアのエネルギー転換系に対するハロゲン化炭化水素の作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In order to investigate the influence of various environmental pollutants on living organisms, the effects of hlogenated hydrocarbons on the mitochondrial membrane were examined. The results obtained were as follows: 1) Monohalogenated benzenes decrease state 3 respiration and increase state 4 respiration, resulting in a decrease in both respiratory control (RCI) and the ADP/O ratio. 2) The above activity is in the decreasing order of iodobenzene, bromobenzene, chlorobenzene and fluorobenzene. This order of activity is parallel to that of potassium releasing activity. 3) Similarly to the effect of monohalogenated benzenes, brominated hydrocarbons also decrease both RCI and the ADP/O ratio. The activity is in the decreasing order of tribromobenzene, dibromobenzene, boron carbide, monobromobenzene and bromoform, which parallels the potassium releasing activity. en-copyright= kn-copyright= en-aut-name=OginoYasuo en-aut-sei=Ogino en-aut-mei=Yasuo kn-aut-name=荻野泰夫 kn-aut-sei=荻野 kn-aut-mei=泰夫 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 en-keyword=ハロゲン化ベンゼン kn-keyword=ハロゲン化ベンゼン en-keyword=ミトコンドリア kn-keyword=ミトコンドリア en-keyword=酸化的燐酸化 kn-keyword=酸化的燐酸化 END start-ver=1.4 cd-journal=joma no-vol=91 cd-vols= no-issue=5-6 article-no= start-page=671 end-page=684 dt-received= dt-revised= dt-accepted= dt-pub-year=1979 dt-pub=19790630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on specific anti-macrophage serum (AMS) I) Preparation of specific rabbit anti-guinea pig peritoneal macrophage serum and its antigen analysis, --including distribution of macrophages in the sites of skin delayed hypersensitivity kn-title=特異的抗マクロファージ血清に関する研究 第一編 特異的抗モルモット腹腔マクロファージ血清の作製 ―特異性の検定と組織内マクロファージの同定― en-subtitle= kn-subtitle= en-abstract= kn-abstract=Macrophage localization in the site of immune response has been investigated using antimacrophage antibody. Specificity of the anti-macrophage sera reported so far has not always been critically evaluated. In the present work, rabbit anti-guinea pig peritoneal macrophage serum (AMS) which reacts specifically with guinea pig macrophages has been successfully prepared by extensive absorptions with various tissues, such as red blood cells, spleen nonadherent cells and kidney homogenate. Specificity of AMS was examined by an immunofluorescent technique and by immunodiffusion. Macrophage specific antigens were analyzed by the sucrose gradient technique. For these, macrophages were fractionated into crude nuclear fraction (M1), crude mitochondrial fraction (M3), crude microsomal fraction (M5) and their supernatants (M4). Each of these fractions was tested by immunodiffusion against AMS with and without absorptions. AMS without absorptions revealed numerous precipitine lines against M1, M3, M4, M5. In contrast, AMS with absorptions showed only one fused precipitin line against M3 and M5. These data, therefore, strongly suggested that the absobed AMS retained antibodies directed at macrophage specific antigens localized in part in the crude mitochondrial and microsomal fractions. Using this specifically prepared AMS, the distributions of macrophages in the site of skin delayed hypersensitivity has also been investigated. en-copyright= kn-copyright= en-aut-name=MiyakeSusumu en-aut-sei=Miyake en-aut-mei=Susumu kn-aut-name=三宅晋 kn-aut-sei=三宅 kn-aut-mei=晋 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第三内科教室 en-keyword=抗マクロファージ血清 kn-keyword=抗マクロファージ血清 en-keyword=特異的抗マクロファージ血清の作製 kn-keyword=特異的抗マクロファージ血清の作製 en-keyword=多臓器吸着 kn-keyword=多臓器吸着 en-keyword=細胞分画法 kn-keyword=細胞分画法 en-keyword=マクロファージ特異抗原の局在 kn-keyword=マクロファージ特異抗原の局在 END start-ver=1.4 cd-journal=joma no-vol=94 cd-vols= no-issue=7-8 article-no= start-page=743 end-page=753 dt-received= dt-revised= dt-accepted= dt-pub-year=1982 dt-pub=19820830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effect of dichlorvos on spermatogenesis of Armigeres subalbatus kn-title=オオクロヤブカArmigeres subalbatusの精子に及ぼすdichlorvosの微細形態学的影響 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The incidence of abnormal spermatozoa in normal and dichlorvos-treated Armigeres subalbatus was examined morphologically by electron microscopy. The mosquitos used in this study had been maintained in the laboratory for 160 generations after being collected in Kanagawa prefecture. For control mosquitos, ten seminal vesicles were removed from male adults 3days after emergence, and sectioned at the middle. The numbers of all normal and abnormal spermatozoa in one side of the double-lumen of a cross-section were counted except for head nucleus parts, tail ends, and tangential sections which could not be identified as normal or abnormal. Normal spermatozoa had 1 flagellum and 2 mitochondrial cords, but abnormal ones had unusual numbers of them. Control mosquitos showed a 4,37% incidence of abnormal spermatozoa as averaged from data on 10 seminal vesicles. For the insecticide treatment, living 4-th stage larvae which were exposed to 0.201ppm of dichlorvos (DDVP) for 24 hours were put back into normal water without DDVP. The seminal vesicles from 10 male adults 3days after emergence were examined likewise to control ones. The count was taken from both sides of the double-lumen of a cross-section. The average incidence of abnormal spermatozoa treated with DDVP was 19.1% which was 4.4 times higher than in control mosquitos. The total number of spermatozoa decreased in vesicles which were treated with DDVP. A large number of abnormal spermatozoa consisted of 1 flagellum and 1 or 3 mitochondria. The wall of seminal vesicles treated with DDVP became thicker than that of controls, and contained many vacuoles in the cytoplasm. en-copyright= kn-copyright= en-aut-name=LaiJim-Shung en-aut-sei=Lai en-aut-mei=Jim-Shung kn-aut-name=頼俊雄 kn-aut-sei=頼 kn-aut-mei=俊雄 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部寄生虫学教室 en-keyword=Armigeres subalbatus kn-keyword=Armigeres subalbatus en-keyword=dichlorvos kn-keyword=dichlorvos en-keyword=ultrastructure kn-keyword=ultrastructure en-keyword=abnormal spermatozoa kn-keyword=abnormal spermatozoa en-keyword=incidence kn-keyword=incidence END start-ver=1.4 cd-journal=joma no-vol=91 cd-vols= no-issue=1-2 article-no= start-page=127 end-page=134 dt-received= dt-revised= dt-accepted= dt-pub-year=1979 dt-pub=19790228 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=(103)Ru for Tumor Scanning Part I. Subcellular distribution of (103)Ru-chloride in tumor and liver kn-title=(103)Ruの腫瘍親和性 第1編 (103)Ru-chlorideの腫瘍および肝臓内分布 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Subcellular distributions of (103)Ru in tumors and livers from Ehrlich's solid tumor-bearing mice (given (103)Ru-chloride intravenously) and in AH-130 ascites hepatoma cells (incubatedin vitro with (103)Ru-chloride) were investigated by differential centrifugation. Fractionations showed that most of the total radioactivity was recovered in the mitochondrial, and cell dibrisplus nuclear, fractions. The highest relative radioactivity per protein was found in the mitochondria1 fraction. These results indicate that (103)Ru accumulates especially in the mitochondria. (97)Ru and (67)Ga in livers showed similar subcellular distributions. en-copyright= kn-copyright= en-aut-name=MizukawaKiichiro en-aut-sei=Mizukawa en-aut-mei=Kiichiro kn-aut-name=水川帰一郎 kn-aut-sei=水川 kn-aut-mei=帰一郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部放射線医学教室 END start-ver=1.4 cd-journal=joma no-vol=93 cd-vols= no-issue=9-10 article-no= start-page=835 end-page=843 dt-received= dt-revised= dt-accepted= dt-pub-year=1981 dt-pub=19811030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Metallic mercury uptake by catalase In Vitro metallic mercury uptake by rat liver dissociated cells, homogenate, cell components, heme protein and ferric ion, with the effect of ethyl and methyl alcohol on the uptake kn-title=金属水銀のカタラーゼによる取り込みに関する研究 第2報 ラット肝の遊離細胞,ホモジネート,細胞内顆粒,へム蛋白質及び3価の鉄イオンによる金属水銀の取り込みとエチルアルコール及びメチルアルコールの作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=In Vitro metallic mercury uptake by rat liver dissociated cells, homogenate, cell components (microbody-rich fraction, mitochondrial fraction and microsomal fraction), heme protein (catalase, cytochrome c, methemoglobin and hematine) and ferric ion were investigated. The effects of ethyl and methyl alcohol on the uptake were also investigated. The following results were obtained. 1) Mercury uptake by rat liver dissociated celld was similar to the uptake by homogenate. 2) Mercury uptake by rat liver homogenate in the presence of hydrogen peroxide was 1.22 times the uptake in the absence of hydrogen peroxide. The uptake by rat liver dissociated cells in the presence of hydrogen peroxide was similar to the uptake in the absence of hydrogen peroxide. 3) Mercury uptake by crystalline catalase, rat liver dissociated cells and homogenate was inhibited by ethtl alcohol and methyl alcohol, though inhibition of catalase activities was not observed. 4) Mercury uptake by rat liver cell components was observed in the order of microbody-rich fraction > microsomal fraction > mitochondrial fraction, and catalase activities were also observed in the order of microbody-rich fraction > microsomal fraction > mitochondrial fraction. Mercury uptake by rat liver cell components was inhibited by potassium cyanide and azide. 5) Cytochrome c, methemoglobin, catalase and ferric ion oxidized metallic mercury in the presence of hydrogen peroxide. In the absence of hydrogen peroxide, methemoglobin and ferric ion oxidized, but catalase and cytochrome c did not oxidize metallic mercury. 6) Hematine did not oxidize metallic mercury with or without hydrogen peroxide. 7) Uptake by ferric ion was inhibited by equimolar addition of EDTA. 8) In the presence of hydrogen peroxide, mercury uptake by catalase was 27,000 times, cytochrome c was 140 times and methemoglobin was 35 times the uptake by ferric ion. Therefore, of heme protein catalase showed the highest mercury uptake. en-copyright= kn-copyright= en-aut-name=KenmotsuKatashi en-aut-sei=Kenmotsu en-aut-mei=Katashi kn-aut-name=劒持堅志 kn-aut-sei=劒持 kn-aut-mei=堅志 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 en-keyword=Catalase kn-keyword=Catalase en-keyword=Cytochrom C kn-keyword=Cytochrom C en-keyword=Methemoglobin kn-keyword=Methemoglobin en-keyword=Cell Components kn-keyword=Cell Components en-keyword=Dissociated Cell kn-keyword=Dissociated Cell END start-ver=1.4 cd-journal=joma no-vol=93 cd-vols= no-issue=3-4 article-no= start-page=219 end-page=225 dt-received= dt-revised= dt-accepted= dt-pub-year=1981 dt-pub=19810430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Experimental Study on Inorganic manganease and Organic manganease(MMT) intoxication 1 Comparison between the effects of MMT and MnCl(2) on oxidative phosphorylation of isolated rat liver mitochondria kn-title=有機及び無機マンガン中毒に関する研究 第1報 分離ラット肝ミトコンドリアの酸化的リン酸化反応に対するMMT及びMnCl(2)の作用比較 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Methylcyclopentadienyl manganease tricarbonyl (MMT) has been developed and used increasingly as a replacement for tetraethyl lead which has been widely used as an antiknock agent of gasoline, or as a fuel oil combustion improver. We, therefore, investigated the effect of MMT on oxidative phosphorylation and K release of mitochondria as an index of toxic effects on biomembranes. The concentrations of solution used were 0.10, 0.25, 0.40 and 0.50 mM. Results obtained were as follows. 1. MMT activated state 4 respiration at more than 0.20 mM solution, i.e. showing the uncoupling phenomenon. 2. Mitochondrial oxidative phosphorylation with MMT was greater than with MnCl. 3. Both MMT and MnCl(2) induced K release from mitochondria, and a dose-response relationship between K release and MMT was recognized. 4. It was considered that one reason for the remarkable difference in uncoupling between MMT and MnCl(2) was the difference in lipid affinity. en-copyright= kn-copyright= en-aut-name=MoritaKeijiro en-aut-sei=Morita en-aut-mei=Keijiro kn-aut-name=森田啓次郎 kn-aut-sei=森田 kn-aut-mei=啓次郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 en-keyword=メチルシクロペンタジェニルマンガン kn-keyword=メチルシクロペンタジェニルマンガン en-keyword=塩化マンガン kn-keyword=塩化マンガン en-keyword=ミトコンドリア kn-keyword=ミトコンドリア en-keyword=酸化的リン酸化 kn-keyword=酸化的リン酸化 en-keyword=K(+)遊出 kn-keyword=K(+)遊出 END start-ver=1.4 cd-journal=joma no-vol=95 cd-vols= no-issue=11-12 article-no= start-page=1117 end-page=1126 dt-received= dt-revised= dt-accepted= dt-pub-year=1983 dt-pub=19831230 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on superoxide production of pulmonary alveolar macrophages. Part. 1. Experimental studies on superoxide production of guinea pig pulmonary alveolar macrophages. kn-title=肺胞マクロファージのスーパーオキサイド産生能に関する研究 第1編 モルモット肺胞マクロファージのスーパーオキサイド産生能に関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=During phagocytosis, pulmonary alveolar macrophages(PAM) produce superoxide (O2), which is highly reactive and bactericidal. Therefore, PAM has an important role in the host defense machanisms in the lung. Generally, patient with diabetes mellitus are susceptible to pulmonary infections. It is supposed that a defect in the bactericidal activity of phagocytes is responsible for pulmonary infection. In this experiment superoxide production formed by PAM stimulated with concanavalin A and cytochalasin D was examined in relation to blood glucose concentration and other conditions. Superoxide production by PAM was maximum when the pH was 7.5, the temperature was 37℃, the glucose concentration was 100mg/dl and Ca(++) concentration was 1mM. A glucose concentration of more than 100mg/dl suppressed the superoxide production, and a high glucose level may be related to the high susceptibility of diabetics of pulmonary infections. The energy of superoxide production by PAM depends on both glycolysis and mitochondrial phosphorylation. On the other hand, polymorphonuclear leucocytes mostly depend on glycolysis. The superoxide dismutase(SOD) activity of PAM is remarkably higher than that of polymorphonuclear leucocytes. en-copyright= kn-copyright= en-aut-name=UedaAkira en-aut-sei=Ueda en-aut-mei=Akira kn-aut-name=上田明 kn-aut-sei=上田 kn-aut-mei=明 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第2内科学教室 en-keyword=スーパーオキサイド (superoxide) kn-keyword=スーパーオキサイド (superoxide) en-keyword=SOD (superoxide dismutase) kn-keyword=SOD (superoxide dismutase) en-keyword=肺胞マクロファージ (pulmonary alveolar macrophage) kn-keyword=肺胞マクロファージ (pulmonary alveolar macrophage) END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=3-4 article-no= start-page=353 end-page=358 dt-received= dt-revised= dt-accepted= dt-pub-year=1984 dt-pub=19840430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Studies on biochemical effects of manganese W; Cooperative effects of manganese and vanadium on the energy transfer reaction of rat liver mitochondria kn-title=マンガンの生体影響に関する研究 第4編 マンガン及びバナジウムのラット肝ミトコンドリアの酸化的リン酸化反応に及ぼす複合作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cooperative effects of Mn(2+) and V(5+) on the energy transfer reaction of rat liver mitochondria were investigated. Mn(2+) (0.10-0.05mM) increased State 4 resperation and decreased State 3 respiration, indicating an uncoupling action on the mitochondria. V(5+) alone at the concentration of 0.1-0.8 mM had no noticeable effect on mitochondrial respiration. In the presence of V(5+), Mn decreased both State 3 and State 4 respiration. The degree of the inhibition was extreme in State 3 respiration at a low concentration of Mn. The change from the accelation of State 4 respiration by Mn(2+) alone to its inhibition by Mn(2+) and V(5+) suggests an incease of cleteriovation in mitochondrial function by the cooperative action of Mn(2+) and V(5+). Cooperative effects of Mn(2+) and Mg(2+) on the energy transfer reaction have been described. In the presence of Mg(2+), the uncoupling action of Mn(2+) was not observed, suggesting that the injurious effect of Mn(2+) on mitochondrial membrane was depressed by Mg(2+). However, phosphorylation activity was more strongly inhibited with Mn(2+) and Mg(2+) together than with Mn(2+) alone. en-copyright= kn-copyright= en-aut-name=MoritaKeijiro en-aut-sei=Morita en-aut-mei=Keijiro kn-aut-name=森田啓次郎 kn-aut-sei=森田 kn-aut-mei=啓次郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生学教室 en-keyword=ミトコンドリア kn-keyword=ミトコンドリア en-keyword=酸化的リン酸化 kn-keyword=酸化的リン酸化 en-keyword=マンガン kn-keyword=マンガン en-keyword=バナジウム kn-keyword=バナジウム en-keyword=マグネシウム kn-keyword=マグネシウム END start-ver=1.4 cd-journal=joma no-vol=95 cd-vols= no-issue=5-6 article-no= start-page=437 end-page=447 dt-received= dt-revised= dt-accepted= dt-pub-year=1983 dt-pub=19830630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Oxidative phosphorylation of mitochondria in digitonin-treated permeable ascites sarcoma cells kn-title=ジギトニン処理permeable腹水肉腫細胞におけるミトコンドリアの酸化的リン酸化 en-subtitle= kn-subtitle= en-abstract=Substrate-permeable cells were prepared by treatment of Rous Sarcoma virus-induced mouse ascites sarcoma cells (SR-C3H/He) with a low concentration of digitonin. Using relatively small amounts of the digitonin-treated permeable cells, mitochondrial functions such as a respiratory rate, respiratory control ratio (RCR), and ADP/O ratio of oxidative phosphorylation were easily measured by the oxygen electrode method. The permeable ascites sarcoma cell mitochondria had a slightly lower RCR and ADP/O ratio than mitochondria isolated from mouse liver and ascites sarcoma cells. This result was found to be mainly due to higher extramitochondrial Mg(2+)-ATPase activity in the permeable ascites sarcoma cells. The effects of hexokinase and pyruvate kinase on the RCR and the ADP/O ratio were investigated by the additions of glucose and phosphoenolpyruvate as substrates, but these enzymes can not be the main factors in decreasing the RCR and the ADP/O ratio in the permeable ascites sarcoma cells since the glycolytic pathway was not continuous in these cells. The digitonin-treated permeable cell system is an extremely useful system for studying mitochondrial functions and their relations to other organelae and metabolic pathways under near in vivo conditions. kn-abstract=ラウス肉腫ウィルス誘発腹水肉腫細胞(SR-C3H/He)を低濃度のジギトニン(終末0.01%)で処理し,基質透過性細胞とすることにより,少量の材料で簡単にミトコンドリアの呼吸速度,呼吸調節率(RCR),酸化的リン酸化能(ADP/0 比)などの機能を酸素電極法を用いて調べられることがわかった.この基質透過性腹水肉腫細胞ではマウス肝や腹水肉腫細胞から分離したミトコンドリアより,呼吸調節率や酸化的リン酸化能が幾分低い.この原因について種々なATPase活性を検討した結果,この透過性細胞では主にミトコンドリア以外のMg(2+)-ATPase活性がかなり高く存在し,これによって呼吸調節率や酸化的リン酸化能の低下が生じることが示唆された.また,この透過性細胞に解糖系の基質であるグルコースやホスホエノールピルビン酸を添加しhexokinaseやpyruvate kinaseの存在による呼吸調節への影響を認めたが,解糖系の一連の反応は不連続であり,呼吸調節率や酸化的リン酸化能の低下の主因であるとは考え難い.このように,低濃度のジギトニン処理透過性細胞は比較的少量のwhole cellでのミトコンドリアの酸化的リン酸化と呼吸阻害剤や脱共役剤の影響を簡便に調べることができ,さらに細胞内オルガネラの機能と代謝系の相関をin vivoに近い条件下で調べることのできるきわめて有用な実験系であると考えられる. en-copyright= kn-copyright= en-aut-name=ShigeharaTsuguya en-aut-sei=Shigehara en-aut-mei=Tsuguya kn-aut-name=茂原嗣也 kn-aut-sei=茂原 kn-aut-mei=嗣也 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部癌源研究施設生化学部 en-keyword=ミトコンドリア kn-keyword=ミトコンドリア en-keyword=透過性細胞 kn-keyword=透過性細胞 en-keyword=酸化的リン酸化 kn-keyword=酸化的リン酸化 en-keyword=ATPase kn-keyword=ATPase en-keyword=ジギトニン kn-keyword=ジギトニン END start-ver=1.4 cd-journal=joma no-vol=98 cd-vols= no-issue=7-8 article-no= start-page=587 end-page=597 dt-received= dt-revised= dt-accepted= dt-pub-year=1986 dt-pub=19860830 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The effect of chlorinated monoaromatic hydrocarbons on biological membranes(Comparison of the effect of chlorobenzenes and chlorophenols on biomembranes) kn-title=塩化ベンゼンの生体膜に対する作用 第W報 分離正常ラット肝ミトコンドリアにおける塩化ベンゼン及び塩化フェノールの作用の比較 en-subtitle= kn-subtitle= en-abstract= kn-abstract=A comparative study on the effect of chlorobenzenes and chlorophenols on mitochondrial membranes was conducted. An increase in chlorine residue from both chlorobenzenes and chlorophenols caused a decrease in respiratory control index (RCI). Chlorophenols acted on biomembranes at a lower concentration than chlorobenzenes. The compounds decreased RCI by increasing state 4 respiration and decreasing state 3 respiration. As the number of chlorine atoms on chlorobenzenes increased, state 3 respiration decreased, causing a decrease in RCI. As the number of chlorine atoms on chlorophenols increased, state 4 respiration increased, causing a decreased in RCI. The amount of potassium released from mitochondrial membranes increased with time after addition of dichlorobenzene and dichlorophenol. A logarithmic increase in potassium release vs. time was observed with dichlorobenzene, and a liner increase in potassium release was observed with dichlorophenol. en-copyright= kn-copyright= en-aut-name=MoriTakaaki en-aut-sei=Mori en-aut-mei=Takaaki kn-aut-name=森孝昭 kn-aut-sei=森 kn-aut-mei=孝昭 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部公衆衛生 en-keyword=ミトコンドリア kn-keyword=ミトコンドリア en-keyword=酸化的リン酸化反応 kn-keyword=酸化的リン酸化反応 en-keyword=塩化ベンゼン類 kn-keyword=塩化ベンゼン類 en-keyword=塩化フェノール類 kn-keyword=塩化フェノール類 en-keyword=K(+)遊出作用 kn-keyword=K(+)遊出作用 END start-ver=1.4 cd-journal=joma no-vol=95 cd-vols= no-issue=3-4 article-no= start-page=387 end-page=393 dt-received= dt-revised= dt-accepted= dt-pub-year=1983 dt-pub=19830430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Partial purification and properties of Ca(2+)-binding protein from rat liver mitochondrial matrix. kn-title=ラット肝ミトコンドリア・マトリクスのCa(2+)結合蛋白質の部分精製とその物性について en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 193-fold purification of Ca(2+)-binding protein from rat liver mitochondrial matrix was achieved. The Ca(2+)-binding protein consisted of 3 polypeptide subunits whose respective molecular weights by SDS polyacrylamide gel electrophoresis were 62K, 49K and 37K. The molecular weight of the protein was 150K to 220K. The Kd for Ca(2+) was 1.3×10-(5)M and lower for Mn(2+) and Mg(2+). The protein was inactivated by heat treatment at 100℃ for 1 min, though stable against treatment with 0.5% w/v trypsin at 37℃ for 30 min. Ruthenium red did not inhibit Ca(2+)-binding. en-copyright= kn-copyright= en-aut-name=TokudaMasaaki en-aut-sei=Tokuda en-aut-mei=Masaaki kn-aut-name=徳田雅明 kn-aut-sei=徳田 kn-aut-mei=雅明 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第一生理学教室 en-keyword=肝ミトコンドリア kn-keyword=肝ミトコンドリア en-keyword=Ca(2+)結合蛋白質 kn-keyword=Ca(2+)結合蛋白質 END start-ver=1.4 cd-journal=joma no-vol=97 cd-vols= no-issue=3-4 article-no= start-page=201 end-page=209 dt-received= dt-revised= dt-accepted= dt-pub-year=1985 dt-pub=19850430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Ferrous ion-induced lipid peroxidation Part I. Analysis of the lag period in liver mitochondria of whole-body irradiated rats. kn-title=二価鉄誘導脂質過酸化反応に関する研究 第一編 全身照射ラット肝ミトコンドリアの二価鉄誘導脂質過酸化反応における誘導時間の解析 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Fe(II)-induced lipid peroxidation was measured at 25℃ by the TBA method in rat liver mitochondria 3 days after 800R of whole-body irradiation, and decrements in Fe(II) concentrations in the medium were measured by the Nitroso-PSAP method, simultaneously. An induction period (lag) was observed in the reaction curve of the Fe(II)-induced lipid peroxidation. The Fe(II) concentration decreased gradually during the lag period, but decreased rapidly thereafter. The oxidating velocity of Fe(II) in the presence of mitochondria was significant compared with the Fe(II) auto-oxidation in the mixture. At a given dose of Fe (II), a greater amount of mitochondrial protein allowed a shortened lag and accelerated the oxidating velocity of Fe (II). The relationship between MDA formation per unit protein and lag time showed the same tendency, so that MDA formation increased with a lengthened lag. With given doses of protein (0.5mg/ml) and Fe(II), a shorter lag and greater MDA formation were found in irradiated rat liver mitochondria than in non-irradiated rat liver mitochondria. With the addition of Fe(II) (0.10mM), the lag was lengthened and MDA formation increased the same in irradiated as in non-irradiated mitochondria, compared with Fe(II) (0.05mM). en-copyright= kn-copyright= en-aut-name=MorimotoSetsuo en-aut-sei=Morimoto en-aut-mei=Setsuo kn-aut-name=森本節夫 kn-aut-sei=森本 kn-aut-mei=節夫 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部放射線医学教室 en-keyword=lipid peroxidation kn-keyword=lipid peroxidation en-keyword=ferrous ion kn-keyword=ferrous ion en-keyword=irradiation kn-keyword=irradiation en-keyword=mitochondria kn-keyword=mitochondria END start-ver=1.4 cd-journal=joma no-vol=100 cd-vols= no-issue=11-12 article-no= start-page=1077 end-page=1087 dt-received= dt-revised= dt-accepted= dt-pub-year=1988 dt-pub=1988 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Evaluation of myocardial protection using continuous measurement of intramyocardial carbon dioxide tension kn-title=心筋保護法の研究 ―心筋組織炭酸ガス分圧連続測定による保護能評価― en-subtitle= kn-subtitle= en-abstract= kn-abstract=To evaluate the effectiveness of myocardial protection during cardiac surgery, continuous measurement was made of the intramyocardial carbon dioxide(PCO(2)) level and pH during aortic cross clamping for 60 minutes under extracorporeal circulation in adult mongrel dogs. Also, samples of myocardium were resected at intervals, and the mitochondrial function and ATP level of these samples were measured in order to judge myocardial injury. The intramyocardial PCO(2) level increased linearly immediately after aortic cross clamping, but after an average of 15.1 minutes, the rate of increase declined. At this point, the ATP levels remained at 70% of the level before aortic cross clamping, and no disturbance of mitochondrial function was found. The intramyocardial pH values revealed slight acidosis. Thus, aortic cross clamping for about 15 minutes did not induce ischemia of the myocardium.It was concluded that monitoring intramyocardial PCO(2) and observing its rate of increase could be useful for determining the effectiveness of myocardial protection during a surgical procedure. en-copyright= kn-copyright= en-aut-name=MizunoYutaka en-aut-sei=Mizuno en-aut-mei=Yutaka kn-aut-name=水野裕 kn-aut-sei=水野 kn-aut-mei=裕 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二外科学教室 en-keyword=心筋保護 kn-keyword=心筋保護 en-keyword=心筋組織炭酸ガス分圧 kn-keyword=心筋組織炭酸ガス分圧 en-keyword=心筋ミトコンドリア機能 kn-keyword=心筋ミトコンドリア機能 en-keyword=心筋内ATP含有量 kn-keyword=心筋内ATP含有量 END start-ver=1.4 cd-journal=joma no-vol=78 cd-vols= no-issue=4-5 article-no= start-page=649 end-page=654 dt-received= dt-revised= dt-accepted= dt-pub-year=1966 dt-pub=19660530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=腹水癌細胞のエネルギー代謝に関する研究 第3編 腹水癌細胞における脂質過酸化反応と脂肪酸組成 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mitochondria isolated from ascites tumor cells have a specific characteristic different from those isolated from normal liver cells, i. e. they do not react with ferrous ion, GSH with GSSG and ascorbic acid, showing no increase in lipid peroxide formation and no swelling. From the viewpoint that this characteristic of tumor cell mitochondria may be due to the specific liqid. compositions of mitochondrial membrane, the author tried to analyze the components of liqids of tumor cells comparing with those of brain, liver, heart, kidney and spleen from normal animals. The following have been revealed; 1. The tumor cells are very low in peroxide formation in the presence of the reducing agents comparing to those from the normal tissues, though the grade of peroxide formation is different in each tissues and by the agents used, and is rather lower in homogenate than in intact mitochondria. 2. Chemical analysis revealed that the lipids from tumor cells is low in unsaturated fatty acid contents, especially C20-polyene contents than those from normal cells. This will be responsible for the low level in lipid peroxidation of the tumor cells. 3. On the basement of the these results discussions has been made on the lipid peroxidation of mitochondria of tumor cells and related mitochondrial swelling under the consideration of enzymic activities. en-copyright= kn-copyright= en-aut-name=NishikazeKeiko en-aut-sei=Nishikaze en-aut-mei=Keiko kn-aut-name=西風桂子 kn-aut-sei=西風 kn-aut-mei=桂子 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部病理学教室 END start-ver=1.4 cd-journal=joma no-vol=103 cd-vols= no-issue=1-2 article-no= start-page=105 end-page=116 dt-received= dt-revised= dt-accepted= dt-pub-year=1991 dt-pub=1991 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Alterations of neuropeptides in MPTP-treated mouse brain kn-title=1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) を用いたパーキンソニズム・モデルマウスにおける脳内神経ペプチドに関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) has been shown to destroy the nigrostriatal dopaminergic system, inducing biochemical and histopathological changes resembling Parkinson's disease. Biochemical changes, especially changes of neuropeptides were determined 1,2 or 6 weeks after MPTP treatment in various regions of the mice brain. The dopamine (DA) concentration decreased to 22% of the control level in the striatum 1 week after MPTP treatment, but recovered to 50% of the control level 6 weeks after MPTP treatment. The decrease in the noradrenaline concentration was less than that of DA. Amine fluorescence histochemistry revealed, markedly decreased amine fluorescnece in the striatum 6 weeks after MPTP treatment, and this decrease in amine fluorescence was recovered after levodopa treatment. The results of a pole thst revealed the bradykinesia of MPTP-treated mice and it was attenuated b y levodopa and amantadine hydrochloride treatments. Among the neuropeptides tested, somatostatin (SOM) increased 1 week after MPTP treatment in the striatum and the thalamus+midbrain but decreased 6 weeks after MPTP treatment in the striatum and the hippocampus. In the striatum the decreased SOM recovered with levodopa treatment. Thus, the SOM might be regulated by a dopaminergic system. On the other hand, in the cerebral cortex, while no changes appeared in the SOM concentration after MPTP treatment, the concentration decreased significantly with levodopa treatment. Other neuropeptides such as substance P, cholecystokinin-octapeptide and thyrotropin releasing hormone did not show any significant changes up to 6 weeks after MPTP treatment. en-copyright= kn-copyright= en-aut-name=KawataMakio en-aut-sei=Kawata en-aut-mei=Makio kn-aut-name=河田牧男 kn-aut-sei=河田 kn-aut-mei=牧男 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部脳代謝研究施設機能生化学部門 en-keyword=MPTP kn-keyword=MPTP en-keyword=parkinsonism kn-keyword=parkinsonism en-keyword=neuropeptide kn-keyword=neuropeptide en-keyword=somatostatin kn-keyword=somatostatin en-keyword=levodopa kn-keyword=levodopa en-keyword=dementia kn-keyword=dementia END start-ver=1.4 cd-journal=joma no-vol=103 cd-vols= no-issue=7-8 article-no= start-page=973 end-page=981 dt-received= dt-revised= dt-accepted= dt-pub-year=1991 dt-pub=199108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The effect of quercetin on thermotolerance in NIH 3T3 cells : From a view point of cell survival kn-title=NIH 3T3 細胞の温熱耐性に対するケルセチンの作用 第1編 細胞の生存率からみたケルセチンの作用 en-subtitle= kn-subtitle= en-abstract= kn-abstract=The inhibition of thermotolerance development by quercetin was examined in NIH 3T3 cells. The cytotoxicity of quercetin increased with the increase in the concentration (10,100μg/ml) and duration (12,48,72 hours) of treatment. The cell killing effect of heat was not enhanced by quercetin (10μg/ml) itself. Quercetin (10μg/ml) inhibited the proliferation of cells for about 72 hours. Quercetin (10μg/ml) delayed the development of thermotolerance, but did not decrease the degree of maximum thermotolerance. Quercetin (10μg/ml) exibited no effect on the decay of thermotolerance. en-copyright= kn-copyright= en-aut-name=KurodaMasahiro en-aut-sei=Kuroda en-aut-mei=Masahiro kn-aut-name=黒田昌宏 kn-aut-sei=黒田 kn-aut-mei=昌宏 aut-affil-num=1 ORCID= en-aut-name=HirakiYoshio en-aut-sei=Hiraki en-aut-mei=Yoshio kn-aut-name=平木祥夫 kn-aut-sei=平木 kn-aut-mei=祥夫 aut-affil-num=2 ORCID= en-aut-name=KawasakiShouji en-aut-sei=Kawasaki en-aut-mei=Shouji kn-aut-name=川崎祥二 kn-aut-sei=川崎 kn-aut-mei=祥二 aut-affil-num=3 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=2 en-affil= kn-affil=岡山大学医学部放射線医学教室 affil-num=3 en-affil= kn-affil=岡山大学医療技術短期大学部 en-keyword=ケルセチン kn-keyword=ケルセチン en-keyword=温熱耐性 kn-keyword=温熱耐性 en-keyword=温熱療法 kn-keyword=温熱療法 END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=3-4 article-no= start-page=401 end-page=413 dt-received= dt-revised= dt-accepted= dt-pub-year=1994 dt-pub=1994 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Kinetics of heat shock protein 72 in HeLa cells after treatment with heating and/or anticancer agents analyzed by a laser cytometer kn-title=レーザーサイトメーターを用いたheat shock protein 72の加温および抗癌剤添加による動態の検討 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Heat shock proteins (HSPs) are regarded as the proteins most related to the development of thermotolerance. Recently, not only their role in thermotolerance, but also their role in resistance to anticancer agents is gathering concern. In this study, the kinetics of hsp 72 in HeLa cells treated with heating and/or anticancer agents were studied. Hsp 72 was immuno-stained by the indirect fluorescent technique using a monoclonal anti-hsp 72 antibody (Amer-sham). The staining pattern was observed and analyzed using a laser cytometer, ACAS 570 (Meridian). Hsp 72 was normally found in the cytoplasm at 37℃ and moved rapidly into the nucleus with heating at 43℃ for 2 hours. It then returned to the cytoplasm 4 to 6 hours after heating. The hsp 72 content reached a peak at 8 hours after heating. Hsp 72 was induced in all cells treated with cisplation, adriamycin, peplomycin, or etoposide for 48 hours. In the cells treated with both heating at 43℃ for 2 hours and these anticancer agents, hsp 72 induction was most suppressed by adriamycin. However, translocation of hsp 72 to the nucleus was specific for heating and was not affected by the anticancer agents. By laser cytometry the intracellular localization of hsp 72 and the changes of its content were simultaneously detected, Moreover, the change pattern of hsp 72 content measured by laser cytomtry coincided with that measured by the Western blotting procedure. en-copyright= kn-copyright= en-aut-name=SawaiHideaki en-aut-sei=Sawai en-aut-mei=Hideaki kn-aut-name=澤井秀秋 kn-aut-sei=澤井 kn-aut-mei=秀秋 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部産科婦人科学教室 en-keyword=レーザーサイトメーター kn-keyword=レーザーサイトメーター en-keyword=heat shock proteinn kn-keyword=heat shock proteinn en-keyword=抗癌剤 kn-keyword=抗癌剤 END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=3-4 article-no= start-page=281 end-page=289 dt-received= dt-revised= dt-accepted= dt-pub-year=1993 dt-pub=1993 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Leukocyte depletion reduced reperfusion injury in hearts preserved hypothermically for 6 hours kn-title=白血球除去による保存心再灌流障害の軽減効果について en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent studies suggest that circulating leukocytes trapped in the post ischemic-reperfused organ release active oxygen species and leukotrienes, and cause tissue damage. Canine hearts statically preserved for six hours, were reperfused with whole blood (group T, n=7), with leukocyte depleted blood (group U, n=14), and with leukocyte and protein depleted blood (group V, n=7). After initial perfusion, whole blood prefusion was started at 15 minutes of post reperfusion (group Ua, n=7) and at 30 minutes of post reperfusion (group Ub, n=7; group V, n=7). Significant leukocytes sequestration wsa demonstrated only in group T and group Ua. Left ventricular function recovery, coronary flow and mitochondrial phospholyration activity were significantly better preserved in the groups reperfused with leukocyte depleted blood, especially gorup V. These date suggest that leukocyte depletion amelioraes reperfusion injury of preserved hearts. en-copyright= kn-copyright= en-aut-name=TeraokaHiromichi en-aut-sei=Teraoka en-aut-mei=Hiromichi kn-aut-name=寺岡広道 kn-aut-sei=寺岡 kn-aut-mei=広道 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二外科学教室 en-keyword=再灌流障害 kn-keyword=再灌流障害 en-keyword=好中球集積 kn-keyword=好中球集積 en-keyword=酸素フリーラジカル kn-keyword=酸素フリーラジカル END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=1-2 article-no= start-page=107 end-page=117 dt-received= dt-revised= dt-accepted= dt-pub-year=1993 dt-pub=19930227 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Myocardial function and metabolism after 24-hour preservation : A comparison of immersion vs perfusion and efficacy of PFC perfusate kn-title=24時間保存心における心筋エネルギー代謝と同所性移植後心機能 ―浸漬保存と灌流保存の比較および PFC 液の有用性について― en-subtitle= kn-subtitle= en-abstract= kn-abstract=To assess the vability of canine hearts after prolonged ex-vivo heart perservation, we evaluated the myocardial metabolism by determining the high energy phosphate(HEP)levels and respiratory function of isolated mitochondria(MRF). Furthermore, we calculated the mitochondrial score(MS) for semi-quantitative analysis of ultrastructural changes. These three indicators were compared with the left ventricular function(LVF) following orthotopic heart transplantation(H-TX). Forty two hearts, harvested from mongrel dogs, each weighing 8.5kg〜15kg, were divided into 3 groups : 24-hour immersion in modified Collins solusion(MC) (group A), 24-hour perfusion with MC(group B) and 24-hour perfusion with MC containing perfluorochemicals(PFC)(group C). After the 24-hour preservation, biopsies were obtained from 7 hearts in each group and HEP levels, MRF and MS were determined. The HEP levels, MRF and MS were significantly higher in group C than in group B and significantly higher in group B than group A. The cardiac function after H-TX revealed a similar tendency. These findings indicate that continuous hypothermic perfusion provides better protection than simple hypothermic immersion and that perfusion with an intracellular solution containing PFC preserves and protects an organ sufficiently before clinical heart transplantation. en-copyright= kn-copyright= en-aut-name=SenoShingo en-aut-sei=Seno en-aut-mei=Shingo kn-aut-name=瀬野晋吾 kn-aut-sei=瀬野 kn-aut-mei=晋吾 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部第二外科学教室 en-keyword=adenine nucleotide kn-keyword=adenine nucleotide en-keyword=ミトコンドリア呼吸能 kn-keyword=ミトコンドリア呼吸能 en-keyword=ミトコンドリアスコア kn-keyword=ミトコンドリアスコア en-keyword=perfluorochemical kn-keyword=perfluorochemical en-keyword=同所性心移植 kn-keyword=同所性心移植 END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=11-12 article-no= start-page=1177 end-page=1181 dt-received= dt-revised= dt-accepted= dt-pub-year=1994 dt-pub=199412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effect of chronic ethanol administration on mitochondrial membrane fluidity in rat liver and kidneys kn-title=長期エタノール投与ラットの肝および腎ミトコンドリア膜の流動性について en-subtitle= kn-subtitle= en-abstract= kn-abstract=The mitochondrial membrane fluidity in the rat liver and kidneys was measured by electron spin resonance spectrometry using spin labels 5- and 16-doxyl stearic acid (5-, 16-DS) after administration of an ethanol solution (7%) for 3 weeks. The order parameter, calculated from the 5-DS spectra, which is utilized for assessing the fluidity of the lipid bilayer near the surface of the membrane, increased significantly in the liver of the ethanol-administered group compared with the control group. No significant difference in the order parameter was observed in the kidney. On the other hand, in the motion parameter from the 16-DS spectra, which is utilized for the core of the lipid bilayer, no significant change was observed in either the liver or the kidneys. These findings indicated that the mitochondrial membrane fluidity decreased, by chronic ethanol administration, in the lipid bilayer near the surface in the rat liver, but no fluidity change was observed in the rat kidney. en-copyright= kn-copyright= en-aut-name=JishoTakayoshi en-aut-sei=Jisho en-aut-mei=Takayoshi kn-aut-name=慈性隆義 kn-aut-sei=慈性 kn-aut-mei=隆義 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部附属分子細胞医学研究施設神経情報学部門 en-keyword=エタノール kn-keyword=エタノール en-keyword=膜流動性 kn-keyword=膜流動性 en-keyword=ミトコンドリア膜 kn-keyword=ミトコンドリア膜 en-keyword=肝臓 kn-keyword=肝臓 en-keyword=腎臓 kn-keyword=腎臓 END start-ver=1.4 cd-journal=joma no-vol=106 cd-vols= no-issue=11-12 article-no= start-page=1117 end-page=1124 dt-received= dt-revised= dt-accepted= dt-pub-year=1994 dt-pub=199412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Effect of isoflurane on energy status of isolated hepatocytes kn-title=イソフルランがラット無酸素下分離肝細胞のエネルギー需給に及ぼす影響 en-subtitle= kn-subtitle= en-abstract= kn-abstract=We investigated the variation in the protection of energy status by isoflurane in isolated hepatocytes with the isoflurane dose, duration of anoxia, and reoxygenation by measurements of ATP, ADP, and AMP, in the cells. During 30 min of anoxia, in the presence of 1.4, 2.8, 4.2% isoflurane the ATP concentration was more than that with 0% isoflurane. With a 30-35 min incubation in the presence of 1.4% isoflurane, there was a modest decrease in energy charge during anoxia, partially prevented by isoflurane and completely reversed by reoxygenation, and no decrease in the total adenine nucleotide. With a 90-120 min incubation, isoflurane partly prevented the decreases in both energy charge and total adenine nucleotide during both anoxia and reoxygenation. We conclude that at doses in the clinical range, isoflurane partially protected isolated hepatocytes against decreases in both energy charge and total adenine nucleotide occurring either during short or long anoxia. en-copyright= kn-copyright= en-aut-name=SamutaTakeshi en-aut-sei=Samuta en-aut-mei=Takeshi kn-aut-name=佐牟田健 kn-aut-sei=佐牟田 kn-aut-mei=健 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部麻酔・蘇生学教室 en-keyword=イソフルラン kn-keyword=イソフルラン en-keyword=分離肝細胞 kn-keyword=分離肝細胞 en-keyword=エネルギーチャージ kn-keyword=エネルギーチャージ en-keyword=高エネルギーリン酸化合物 kn-keyword=高エネルギーリン酸化合物 END start-ver=1.4 cd-journal=joma no-vol=105 cd-vols= no-issue=7-8 article-no= start-page=673 end-page=680 dt-received= dt-revised= dt-accepted= dt-pub-year=1993 dt-pub=199308 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Experimental studies on nicaraven as a radioprotector : Survival ratio of mice, spleen colony formation, blood picture and lipid peroxidation kn-title=ニカラベンの放射線防護剤としての有用性の検討―マウス生存率,脾コロニー,末梢血液像,脂質過酸化について― en-subtitle= kn-subtitle= en-abstract= kn-abstract=The degree of radiation protection from Nicaraven after whole-body irradiation was investigated in C3H mice. Nicaraven is a free radical scavenging agent, which was shown to improve brain edema and blood flow. Nicaraven was injected intraperitoneally in mice before and/or after whole-body irradiation with 640cGy or 740cGy using Toshiba Lineac LMR-4C (4MV, 6.45×10(-2)C/s/min). The 30 day survival ratio was improved significantly by Nicaraven (P≦0.02). Endogenous spleen colony formation was investigated after 640cGy. The agent was injected before (pre), after (post) or before and after irradiation (pre-post), and compared with the untreated group (control). Nine days after irradiation, the mean colony formation was 2.00 (pre), 3.09 (post), 4.31 (pre-post) and 1.47 (control). The differences between pre and post (p≦0.01), between pre-post and control (p≦0.01) and between post and control (p≦0.05) were significant. Nicaraven induced recovery of leukocyte and lymphocyte counts after irradiation, but not that of erythrocytes. The effect of the agent on mice liver mitochondrial lipid peroxidation was also investigated. The lag time was not shortened, but reduction of the TBA value was observed. Nicaraven was not only recognized as a radioprotector, but its ability to promote recovery from the damage caused by irradiation was also suggested. en-copyright= kn-copyright= en-aut-name=MoriYasutane en-aut-sei=Mori en-aut-mei=Yasutane kn-aut-name=森泰胤 kn-aut-sei=森 kn-aut-mei=泰胤 aut-affil-num=1 ORCID= en-aut-name=TakashimaHitoshi en-aut-sei=Takashima en-aut-mei=Hitoshi kn-aut-name=高島均 kn-aut-sei=高島 kn-aut-mei=均 aut-affil-num=2 ORCID= en-aut-name=SeoHiroyuki en-aut-sei=Seo en-aut-mei=Hiroyuki kn-aut-name=瀬尾裕之 kn-aut-sei=瀬尾 kn-aut-mei=裕之 aut-affil-num=3 ORCID= en-aut-name=OhkawaMotoomi en-aut-sei=Ohkawa en-aut-mei=Motoomi kn-aut-name=大川元臣 kn-aut-sei=大川 kn-aut-mei=元臣 aut-affil-num=4 ORCID= en-aut-name=TanabeMasatada en-aut-sei=Tanabe en-aut-mei=Masatada kn-aut-name=田邉正忠 kn-aut-sei=田邉 kn-aut-mei=正忠 aut-affil-num=5 ORCID= en-aut-name=YamamotoGoki en-aut-sei=Yamamoto en-aut-mei=Goki kn-aut-name=山本剛禧 kn-aut-sei=山本 kn-aut-mei=剛禧 aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=香川医科大学放射線医学教室 affil-num=2 en-affil= kn-affil=香川医科大学放射線医学教室 affil-num=3 en-affil= kn-affil=香川医科大学放射線医学教室 affil-num=4 en-affil= kn-affil=香川医科大学放射線医学教室 affil-num=5 en-affil= kn-affil=香川医科大学放射線医学教室 affil-num=6 en-affil= kn-affil=岡山大学医療技術短期大学部診療放射線技術学科 en-keyword=Radioprotector kn-keyword=Radioprotector en-keyword=Nicaraven kn-keyword=Nicaraven en-keyword=Radical scavenger kn-keyword=Radical scavenger en-keyword=Spleen colony kn-keyword=Spleen colony en-keyword=Lipid peroxidation kn-keyword=Lipid peroxidation END start-ver=1.4 cd-journal=joma no-vol=107 cd-vols= no-issue=7-8 article-no= start-page=91 end-page=98 dt-received= dt-revised= dt-accepted= dt-pub-year=1995 dt-pub=19950831 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Immobilization stress affected free radicals, superoxide dismutase activity and thiobarbituric acid reactive substances in the rat brain kn-title=拘束スレレスのラット脳内フリーラジカル, スーパーオキシドジスムターゼ活性およびチオバルビツール酸反応物質への影響に関する研究 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immobilization stress for 6 hours induced hemorrhagic erosion in the rat stomach. Hydroxyl radicals singnificantly increased in the pons-medulla oblongata in stressed rats. Mitochondrial superoxide dismutase (SOD) activity was enhanced in the midbrain but was lowered in the cortex, hippocampus and cerebellum in stressed rats. Thiobarbituric acid reactive substances increased by stress in the cortex and midbrain. These finding suggested that immobilization stress generated hydroxyl radicals and accelerated lipid peroxidation, and affected mitocho-drial SOD activity which may lead to neuronal damage in stressed rats. en-copyright= kn-copyright= en-aut-name=OkamuraYouko en-aut-sei=Okamura en-aut-mei=Youko kn-aut-name=岡村容子 kn-aut-sei=岡村 kn-aut-mei=容子 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学医学部附属分子細胞医学研究施設神経情報学部門 en-keyword=拘束ストレス kn-keyword=拘束ストレス en-keyword=ヒドロキシルラジカル kn-keyword=ヒドロキシルラジカル en-keyword=スーパーオキシドジスムターゼ活性 kn-keyword=スーパーオキシドジスムターゼ活性 en-keyword=チオバルビツール酸反応物質 kn-keyword=チオバルビツール酸反応物質 en-keyword=脳 kn-keyword=脳 END start-ver=1.4 cd-journal=joma no-vol=116 cd-vols= no-issue=1 article-no= start-page=9 end-page=16 dt-received= dt-revised= dt-accepted= dt-pub-year=2004 dt-pub=20040531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=心不全における酸化ストレスの関与:基礎的ならびに臨床的検討 ―岡山大学医学賞(結城賞)を受賞して― en-subtitle= kn-subtitle= en-abstract= kn-abstract=心不全患者において血中の過酸化脂質の上昇などが報告され,活性酸素による酸化ストレスの関与が示唆されている.そこで,心筋が実際に活性酸素を発生するかどうかを,活性酸素を検出する蛍光プローブを用いてラットの培養心筋細胞において検討した.心不全増悪因子であるアンジオテンシンIIおよびtumor necrosis factor(TNF)-alphaを加えると心筋細胞で濃度依存性に活性酸素が発生した.さらにヒトの不全心筋においても実際に酸化ストレスの発生が増強しているかを検討した.過酸化脂質の代謝産物で,有害なアルデヒドである4-Hydroxy-2-nonenal(HNE)によって修飾された蛋白質を免疫染色にて調べたところ,拡張型心筋症患者の心筋において正常心機能者に比べ5倍以上増加していた.さらにβ遮断薬(Carvedilol)により治療を行ったところ心機能の改善とともに,HNE修飾蛋白質が40%低下した.以上の一連の研究により, 活性酸素による酸化ストレスの発生が不全心筋において増強しており,その抑制が心不全治療のターゲットの一つになりうることを明らかにした. en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=中村一文 kn-aut-sei=中村 kn-aut-mei=一文 aut-affil-num=1 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=草野研吾 kn-aut-sei=草野 kn-aut-mei=研吾 aut-affil-num=2 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=垣下幹夫 kn-aut-sei=垣下 kn-aut-mei=幹夫 aut-affil-num=3 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=三浦綾 kn-aut-sei=三浦 kn-aut-mei=綾 aut-affil-num=4 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=久松研一 kn-aut-sei=久松 kn-aut-mei=研一 aut-affil-num=5 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=西井伸洋 kn-aut-sei=西井 kn-aut-mei=伸洋 aut-affil-num=6 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=伴場主一 kn-aut-sei=伴場 kn-aut-mei=主一 aut-affil-num=7 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=渡邊敦之 kn-aut-sei=渡邊 kn-aut-mei=敦之 aut-affil-num=8 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=藤尾栄起 kn-aut-sei=藤尾 kn-aut-mei=栄起 aut-affil-num=9 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=宮地克維 kn-aut-sei=宮地 kn-aut-mei=克維 aut-affil-num=10 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=永瀬聡 kn-aut-sei=永瀬 kn-aut-mei=聡 aut-affil-num=11 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=森田宏 kn-aut-sei=森田 kn-aut-mei=宏 aut-affil-num=12 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=斎藤博則 kn-aut-sei=斎藤 kn-aut-mei=博則 aut-affil-num=13 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=江森哲郎 kn-aut-sei=江森 kn-aut-mei=哲郎 aut-affil-num=14 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=浅沼幹人 kn-aut-sei=浅沼 kn-aut-mei=幹人 aut-affil-num=15 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=宮崎正博 kn-aut-sei=宮崎 kn-aut-mei=正博 aut-affil-num=16 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=中村陽一 kn-aut-sei=中村 kn-aut-mei=陽一 aut-affil-num=17 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=松原広己 kn-aut-sei=松原 kn-aut-mei=広己 aut-affil-num=18 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=伏見和郎 kn-aut-sei=伏見 kn-aut-mei=和郎 aut-affil-num=19 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=豊國伸哉 kn-aut-sei=豊國 kn-aut-mei=伸哉 aut-affil-num=20 ORCID= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=大江透 kn-aut-sei=大江 kn-aut-mei=透 aut-affil-num=21 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=4 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=6 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=7 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=8 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=9 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=10 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=11 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=12 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=13 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=14 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 affil-num=15 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 神経情報学 affil-num=16 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 細胞生物学 affil-num=17 en-affil= kn-affil=松山市民病院循環器内科 affil-num=18 en-affil= kn-affil=国立病院岡山医療センター循環器科 affil-num=19 en-affil= kn-affil=北陸先端科学技術大学院大学ナノマテリアルテクノロジーセンター affil-num=20 en-affil= kn-affil=京都大学大学院医学研究科病態生物医学 affil-num=21 en-affil= kn-affil=岡山大学大学院医歯学総合研究科 循環器内科 en-keyword=4-Hydroxy-2-nonenal kn-keyword=4-Hydroxy-2-nonenal en-keyword=酸化ストレス kn-keyword=酸化ストレス en-keyword=心不全 kn-keyword=心不全 en-keyword=β遮断薬 kn-keyword=β遮断薬 END