Journal
FREE RADICAL RESEARCH
Volume 45, Issue 3, Pages 342-350Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10715762.2010.532496
Keywords
Oxidative stress; cell death; 6-hydroxydopamine; Parkinson's disease; signal transduction
Categories
Funding
- Special Coordination Fund for Science and Technology
- Ministry of Education, Culture, Sports, Science and Technology, Japan [21780267]
- Japan Health Foundation
- Grants-in-Aid for Scientific Research [21780267, 21380185] Funding Source: KAKEN
Ask authors/readers for more resources
6-Hydroxydopamine (6-OHDA) is a neurotoxin that has been widely used to generate Parkinson's disease (PD) models. Increased oxidative stress is suggested to play an important role in 6-OHDA-induced cell death. Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66shc, this study investigated the role of p66shc in the cytotoxicity of 6-OHDA. 6-OHDA induced cell death and p66shc phosphorylation at Ser36 in SH-SY5Y cells. Pre-treatment with the protein kinase C beta (PKC beta) inhibitor hispidin suppressed 6-OHDA-induced p66shc phosphorylation. Elimination of H2O2 by catalase reduced cell death and p66shc phosphorylation induced by 6-OHDA. Cells deficient in p66shc were more resistant to 6-OHDA-induced cell death than wild-type cells. Furthermore, reconstitution of wild-type p66shc, but not the S36A mutant, in p66shc-deficient cells increased susceptibility to 6-OHDA. These results indicate that H2O2 derived from 6-OHDA is an important mediator of cell death and p66shc phosphorylation induced by 6-OHDA and that p66shc phosphorylation at Ser36 is indispensable for the cytotoxicity of 6-OHDA.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available