Journal article

Zinc induces CDK5 activation and neuronal death through CDK5-Tyr15 phosphorylation in ischemic stroke

Qing-Zhang Tuo, Zhen-Yu Liuyang, Peng Lei, Xiong Yan, Yang-Ping Shentu, Jia-Wei Liang, Huan Zhou, Lei Pei, Yan Xiong, Tong-Yao Hou, Xin-Wen Zhou, Qun Wang, Jian-Zhi Wang, Xiao-Chuan Wang, Rong Liu

Cell Death & Disease | NATURE PUBLISHING GROUP | Published : 2018

Abstract

CDK5 activation promotes ischemic neuronal death in stroke, with the recognized activation mechanism being calpain-dependent p35 cleavage to p25. Here we reported that CDK5-Tyr15 phosphorylation by zinc induced CDK5 activation in brain ischemic injury. CDK5 activation and CDK5-Tyr15 phosphorylation were observed in the hippocampus of the rats that had been subjected to middle cerebral artery occlusion, both of which were reversed by pretreatment with zinc chelator; while p35 cleavage and calpain activation in ischemia were not reversed. Zinc incubation resulted in CDK5-Tyr15 phosphorylation and CDK5 activation, without increasing p35 cleavage in cultured cells. Site mutation experiment confi..

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Grants

Awarded by National Natural Science Foundation of China


Awarded by Natural Science Foundation of Hubei Province, China


Awarded by Fundamental Research Funds for the Central Universities, HUST


Funding Acknowledgements

This work was supported by the National Natural Science Foundation of China (no.: 81471304, 31771189, 81571078) (R.L. and L.P.), Natural Science Foundation of Hubei Province, China (no.: 2017CFA065) (R.L.), Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST (J.-Z.W.) and Fundamental Research Funds for the Central Universities, HUST (no.: 2015XJGH013) (R.L.).