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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
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
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
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
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
出版物タイトル
Brain Research
1206巻
開始ページ
1
終了ページ
12
資料タイプ
学術雑誌論文
言語
English
査読
有り
DOI
Web of Science KeyUT
Submission Path
neuroscience/3