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Zhou M.,Xuanwu Hospital of Capital | Xu S.,Xuanwu Hospital of Capital | Mi J.,Xuanwu Hospital of Capital | Ueda K.,Xuanwu Hospital of Capital | And 2 more authors.
Brain Research | Year: 2013

α-Synuclein (α-syn) and oxidative stress play pivotal roles in the pathogenesis of Parkinson's disease (PD). However, the mechanisms underlying the interaction between α-syn and oxidative stress remain poorly understood. The present study provides evidence to suggest that the nuclear translocation of α-syn increases death of dopaminergic neurons in response to oxidative stress. We found that administration of H2O2 induced a rapid cleavage and nuclear translocation of α-syn in cultured MES23.5 cells. Inhibition of calpain proteolysis, using a calpain inhibitor (MDL-28170), significantly blocked cleavage and nuclear translocation of α-syn and attenuated H2O2-induced cell death in MES23.5 cells. Expression of a truncated fragment of α-syn (58-140) significantly increased the cell death induced by H2O2 treatment. These results suggest that calpain proteolysis is involved in the process of nuclear translocation of α-syn in MES23.5 dopaminergic cells induced by oxidative stress, and that nuclear translocation of α-syn increases susceptibility of these cells to oxidative stress. Taken together, our findings provide new insight into the interaction between α-syn and oxidative stress through activation of calpain proteolytic activity. © 2013 Elsevier B.V. Source

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