ID | 32936 |
FullText URL | |
Author |
Shiosaka, Masahiko
Ogino, Tetsuya
researchmap
Okimura, Yuya
Utsumi, Toshihiko
Sato, Eisuke F.
Akagi, Reiko
Inoue, Masayasu
Utsumi, Kozo
|
Abstract | 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. |
Keywords | apoptosis
glutathione
gamma-glutamylcysteine synthetase; heme oxygenase-1
6-hydroxydopamine
alpha-lipoic acid
Nrf2
|
Note | 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. |
Published Date | 2008-06-23
|
Publication Title |
Brain Research
|
Volume | volume1206
|
Start Page | 1
|
End Page | 12
|
Content Type |
Journal Article
|
language |
English
|
Refereed |
True
|
DOI | |
Web of Science KeyUT | |
Submission Path | neuroscience/3
|