title: Nuclear translocation of alpha-synuclein increases susceptibility of MES23.5 cells to oxidative stress.
abstract: 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.
authors: Department of Neurobiology and the Sino-Japan Joint Laboratory of Neurodegenerative Diseases, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital University of Medical Sciences, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors: Ming
authors: M
authors: Zhou
authors: Shengli
authors: S
authors: Xu
authors: Jiaojiao
authors: J
authors: Mi
authors: Kenji
authors: K
authors: Uéda
authors: Piu
authors: P
authors: Chan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004151:Dipeptides / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D004151:Dipeptides; D051844:alpha-Synuclein; D006861:Hydrogen Peroxide; D002154:Calpain; D002118:Calcium; C058076:calpain inhibitor III