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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
Source PublicationJOURNAL OF MOLECULAR CELL BIOLOGY
ISSN1674-2788
SubtypeArticle
Volume3Issue:4Pages:239-249
Contribution Rank2
AbstractAlthough 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.
Keywordnitric oxide nitration neuronal death toxicity focal adhesion kinase calcium-independent inducible nitric oxide synthase
Subject AreaPhysiological Psychology/biological Psychology
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Indexed BySCI
Language英语
Funding OrganizationChina 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]
Project Intro.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 IDWOS:000293624000006
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Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/10852
Collection脑与认知科学国家重点实验室
Corresponding AuthorHe, RQ (reprint author), Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, 15 Datun Rd, Beijing 100101, Peoples R China.
Affiliation1.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
Recommended Citation
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.
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