A novel molecular mechanism for nitrated alpha-synuclein-induced cell death

	A novel molecular mechanism for nitrated alpha-synuclein-induced cell death
	Liu, Yanying 1; Qiang, Min 1; Wei, Yan 1; He, Rongqiao 1,2; He, RQ (reprint author), Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, 15 Datun Rd, Beijing 100101, Peoples R China.
心理所单位排序	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
	2011-08-01
语种	英语
发表期刊	JOURNAL OF MOLECULAR CELL BIOLOGY
ISSN	1674-2788
卷号	3 期号:4 页码:239-249
期刊论文类型	Article
URL	查看原文
收录类别	SCI
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
资助机构	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]
引用统计	被引频次：70[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
第一作者单位	脑与认知科学国家重点实验室
推荐引用方式 GB/T 7714	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.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
WOS000293624000006.p（531KB）	期刊论文	出版稿	限制开放	Apache License	请求全文