机构：[a]Department of Neurobiology and the Sino-Japan Joint Laboratory of Neurodegenerative Diseases, Beijing Institute of Geriatrics, XuanwuHospital of Capital University of Medical Sciences, Key Laboratory for Neurodegenerative Diseases of Ministry of Education,Beijing 1OOO53, China[b]Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa,Setagaya-ku, Tokyo 156-8506, Japan
alpha-Synuclein (alpha-syn) and oxidative stress play pivotal roles in the pathogenesis of Parkinson's disease (PD). However, the mechanisms underlying the interaction between alpha-syn and oxidative stress remain poorly understood. The present study provides evidence to suggest that the nuclear translocation of alpha-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 alpha-syn in cultured MES23.5 cells. Inhibition of calpain proteolysis, using a calpain inhibitor (MDL-28170), significantly blocked cleavage and nuclear translocation of alpha-syn and attenuated H2O2-induced cell death in MES23.5 cells. Expression of a truncated fragment of alpha-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 alpha-syn in MES23.5 dopaminergic cells induced by oxidative stress, and that nuclear translocation of alpha-syn increases susceptibility of these cells to oxidative stress. Taken together, our findings provide new insight into the interaction between alpha-syn and oxidative stress through activation of calpain proteolytic activity. (C) 2013 Elsevier B.V. All rights reserved.
基金：
the National Natural ScienceFoundation (No.3067 1950)
the National High TechnologyResearch and Development Program (No. 2006AA02A408)
第一作者机构：[a]Department of Neurobiology and the Sino-Japan Joint Laboratory of Neurodegenerative Diseases, Beijing Institute of Geriatrics, XuanwuHospital of Capital University of Medical Sciences, Key Laboratory for Neurodegenerative Diseases of Ministry of Education,Beijing 1OOO53, China
通讯作者：
通讯机构：[a]Department of Neurobiology and the Sino-Japan Joint Laboratory of Neurodegenerative Diseases, Beijing Institute of Geriatrics, XuanwuHospital of Capital University of Medical Sciences, Key Laboratory for Neurodegenerative Diseases of Ministry of Education,Beijing 1OOO53, China
推荐引用方式(GB/T 7714)：
Ming Zhou,Shengli Xu,Jiaojiao Mi,et al.Nuclear translocation of alpha-synuclein increases susceptibility of MES23.5 cells to oxidative stress[J].BRAIN RESEARCH.2013,1500:doi:10.1016/j.brainres.2013.01.024.
APA：
Ming Zhou,Shengli Xu,Jiaojiao Mi,Kenji Uéd&Piu Chan.(2013).Nuclear translocation of alpha-synuclein increases susceptibility of MES23.5 cells to oxidative stress.BRAIN RESEARCH,1500,
MLA：
Ming Zhou,et al."Nuclear translocation of alpha-synuclein increases susceptibility of MES23.5 cells to oxidative stress".BRAIN RESEARCH 1500.(2013)
