Journal article
Phosphorylation of p66shc mediates 6-hydroxydopamine cytotoxicity
Free radical research, Vol.45(3), pp.342-350
03/2011
DOI: 10.3109/10715762.2010.532496
PMID: 21047172
Abstract
Abstract
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 β (PKCβ) 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.
Details
- Title: Subtitle
- Phosphorylation of p66shc mediates 6-hydroxydopamine cytotoxicity
- Creators
- Tohru Yamamori - Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, JapanAyano Mizobata - Department of Medical Life Systems, Faculty of Medical and Life Sciences, Doshisha University, Kyotanabe, Kyoto, JapanYoshiro Saito - Department of Medical Life Systems, Faculty of Medical and Life Sciences, Doshisha University, Kyotanabe, Kyoto, JapanYasuomi Urano - Department of Medical Life Systems, Faculty of Medical and Life Sciences, Doshisha University, Kyotanabe, Kyoto, JapanOsamu Inanami - Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, JapanKaikobad Irani - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Philadelphia, USANoriko Noguchi - Department of Medical Life Systems, Faculty of Medical and Life Sciences, Doshisha University, Kyotanabe, Kyoto, Japan
- Resource Type
- Journal article
- Publication Details
- Free radical research, Vol.45(3), pp.342-350
- Publisher
- Informa Healthcare
- DOI
- 10.3109/10715762.2010.532496
- PMID
- 21047172
- ISSN
- 1071-5762
- eISSN
- 1029-2470
- Language
- English
- Date published
- 03/2011
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984047607402771
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