ID | 32936 |
フルテキストURL | |
著者 |
Fujita, Hirofumi
Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Shiosaka, Masahiko
Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ogino, Tetsuya
Department of Pathological Research, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Okimura, Yuya
Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Utsumi, Toshihiko
Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University
Sato, Eisuke F.
Department of Biochemistry and Molecular Pathology Osaka City University Medical School
Akagi, Reiko
Faculty of Health and Welfare Science, Okayama Prefectural University
Inoue, Masayasu
Department of Biochemistry and Molecular Pathology Osaka City University Medical School
Utsumi, Kozo
Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sasaki, Junzo
Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | We previously reported that the generation of reactive oxygen species (ROS) is the initial event in cell death induced by 6-hydroxydopamine (6-OHDA), an experimental model of Parkinsonism. Since recent studies suggested the important role of antioxidant activity of alpha-lipoic acid (LA) in the suppression of apoptosis of various types, we studied the effect on 6-OHDA-induced apoptosis of PC12 cells. Biochemical analysis revealed that LA suppressed the 6-OHDA-induced ROS generation, increase of caspase-like activity and chromatin condensation. The suppression of 6-OHDA-induced apoptosis by LA required pre-incubation of PC12 cells with LA for 12-24 h. LA increased the intracellular levels of heme oxygenase-1 (HO-1) and glutathione (GSH) and stimulated the expression of GSH synthesis-related genes such as cystine/glutamate antiporter and gamma-glutamylcysteine synthetase (gamma-GCS). However, Sn-mesoporphyrin IX, an inhibitor of HO-1, did not attenuate the LA-induced suppression of apoptosis. In contrast, buthionine sulfoximine, an inhibitor of gamma-GCS, attenuated the LA-induced suppression of ROS generation and chromatin condensation. in addition, a transcription factor Nrf2, which regulates the expression of antioxidant enzymes such as gamma-GCS, translocated to the nucleus by LA. These results suggested that LA suppressed the 6-OHDA induced-apoptosis by the increase in cellular glutathione through stimulation of the GSH synthesis system but not by the expression of HO-1. |
キーワード | apoptosis
glutathione
gamma-glutamylcysteine synthetase; heme oxygenase-1
6-hydroxydopamine
alpha-lipoic acid
Nrf2
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備考 | Published with permission from the copyright holder.
This is a author's copy,as published in Brain Research , 2008 Vol.1206 pp.1-12 Publisher URL: http://dx.doi.org/10.1016/j.brainres.2008.01.081 Direct access to Thomson Web of Science record Copyright © 2008 by Elsevier B.V. |
発行日 | 2008-06-23
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出版物タイトル |
Brain Research
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巻 | 1206巻
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開始ページ | 1
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終了ページ | 12
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資料タイプ |
学術雑誌論文
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言語 |
英語
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査読 |
有り
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DOI | |
Web of Science KeyUT | |
Submission Path | neuroscience/3
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