Phosphorylation of p66shc mediates 6-hydroxydopamine cytotoxicity

Tohru Yamamori, Ayano Mizobata, Yoshiro Saito, Yasuomi Urano, Osamu Inanami, Kaikobad Irani, Noriko Noguchi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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 H 2O2 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 H 2O2 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.

Original languageEnglish
Pages (from-to)342-350
Number of pages9
JournalFree Radical Research
Issue number3
Publication statusPublished - 2011 Mar


  • 6-hydroxydopamine
  • cell death
  • Oxidative stress
  • Parkinson' s disease
  • signal transduction


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