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A novel molecular mechanism for nitrated alpha-synuclein-induced cell death
Liu, Yanying1; Qiang, Min1; Wei, Yan1; He, Rongqiao1,2; He, RQ (reprint author), Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, 15 Datun Rd, Beijing 100101, Peoples R China.
2011-08-01
发表期刊JOURNAL OF MOLECULAR CELL BIOLOGY
ISSN1674-2788
文章类型Article
卷号3期号:4页码:239-249
产权排序2
摘要Although previous studies have demonstrated the involvement of nitrated alpha-synuclein in neurodegenerative disorders (synucleinopathies), the effects of nitrated alpha-synuclein and the molecular mechanisms underlying its toxicity are still unclear. In the present study, nitrated alpha-synuclein with four 3-nitrotyrosines (Tyr(39), Tyr(125), Tyr(133), and Tyr(136)) was obtained non-enzymatically by incubation with nitrite. The nitrated protein existed as a mixture of monomers, dimers, and polymers in solution. The nitrated alpha-synuclein could induce cell death in a time-and concentration-dependent manner when SH-SY5Y cells (a human neuroblastoma cell line) were incubated with the dimers and polymers. Treatment with anti-integrin alpha 5 beta 1 antibody partially rescued the SH-SY5Y cells from the cell death. Dot blotting and immunoprecipitation revealed that the nitrated protein bound to integrin on the cell membranes. Level of nitric oxide (NO) and calcium-independent inducible NO synthase (iNOS) activity increased during the initial stages of the treatment. The expression of phosphorylated focal adhesion kinase (FAK) decreased in the cells. Subsequently, an increase in caspase 3 activity was observed in SH-SY5Y cells. Our results demonstrate that activation of iNOS and inhibition of FAK may both be responsible for the cell death induced by nitrated alpha-synuclein. These data suggest that the cytotoxicity of nitrated alpha-synuclein is mediated via an integrin-iNOS/-FAK signaling pathway, and that the nitration of alpha-synuclein plays a role in neuronal degeneration.
关键词nitric oxide nitration neuronal death toxicity focal adhesion kinase calcium-independent inducible nitric oxide synthase
学科领域Physiological Psychology/biological Psychology
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收录类别SCI
语种英语
项目资助者China Postdoctoral Science Foundation [20070410153, 200801120] ; National Science Foundation of China [30970695] ; Major State Basic Research Development Program of China (973 Program) [2010CB912303] ; Chinese Academy of Sciences [KSCX2-YW-R-119, KSCX2-YW-R-256]
项目简介This work was supported by the grants from the China Postdoctoral Science Foundation (20070410153, 200801120), the National Science Foundation of China (30970695), the Major State Basic Research Development Program of China (973 Program) (2010CB912303), and the Chinese Academy of Sciences (KSCX2-YW-R-119, KSCX2-YW-R-256).
WOS记录号WOS:000293624000006
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被引频次:42[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/10852
专题脑与认知科学国家重点实验室
通讯作者He, RQ (reprint author), Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, 15 Datun Rd, Beijing 100101, Peoples R China.
作者单位1.Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
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Liu, Yanying,Qiang, Min,Wei, Yan,et al. A novel molecular mechanism for nitrated alpha-synuclein-induced cell death[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2011,3(4):239-249.
APA Liu, Yanying,Qiang, Min,Wei, Yan,He, Rongqiao,&He, RQ .(2011).A novel molecular mechanism for nitrated alpha-synuclein-induced cell death.JOURNAL OF MOLECULAR CELL BIOLOGY,3(4),239-249.
MLA Liu, Yanying,et al."A novel molecular mechanism for nitrated alpha-synuclein-induced cell death".JOURNAL OF MOLECULAR CELL BIOLOGY 3.4(2011):239-249.
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