Extracellular alpha-synuclein induces calpain-dependent overactivation of cyclin-dependent kinase 5 in vitro

被引：25

作者：

Czapski, Grzegorz A. ^{[1
]}

Gassowska, Magdalena ^{[1
]}

Wilkaniec, Anna ^{[1
]}

Cieslik, Magdalena ^{[1
]}

Adamczyk, Agata ^{[1
]}

机构：

[1] Polish Acad Sci, Mossakowski Med Res Ctr, Dept Cellular Signalling, PL-02106 Warsaw, Poland

来源：

FEBS LETTERS | 2013年 / 587卷 / 18期

关键词：

Parkinson's disease; Alpha-synuclein; Cyclin-dependent kinase 5; Phosphorylation; p35; Calpain; CELL-DEATH; CDK5-MEDIATED PHOSPHORYLATION; PHEOCHROMOCYTOMA CELLS; PARKINSONS-DISEASE; LEWY BODIES; CDK5; ACTIVATION; P53; TRANSMISSION; SECRETION;

D O I：

10.1016/j.febslet.2013.07.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Extracellular alpha-synuclein (ASN) could be involved in the pathomechanism of Parkinson's disease (PD) via disturbances of calcium homeostasis, activation of nitric oxide synthase and oxidative/nitrosative stress. In this study we analyzed the role of cyclin-dependent kinase 5 (Cdk5) in the molecular mechanism(s) of ASN toxicity. We found that exposure of PC12 cells to ASN increases Cdk5 activity via calpain-dependent p25 formation and by enhancement of Cdk5 phosphorylation at Tyr15. Cdk5 and calpain inhibitors prevented ASN-evoked cell death. Our findings, indicating the participation of Cdk5 in ASN toxicity, provide new insight into how extracellular ASN may trigger dopaminergic cell dysfunction in PD. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：3135 / 3141

页数：7

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