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In Vitro Cell Dev Biol Anim. 2016 Jun;52(6):690-8. doi: 10.1007/s11626-016-0039-8. Epub 2016 Apr 29.

Heat shock protein 70 inhibits cardiomyocyte necroptosis through repressing autophagy in myocardial ischemia/reperfusion injury.

Liu X1,2, Zhang C2,3, Zhang C2,3, Li J2,3, Guo W2,3, Yan D2,4, Yang C2,4, Zhao J2,4, Xia T1, Wang Y1, Xu R1, Wu X5,6, Shi J7,8.

Author information

1
Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
2
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
3
Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, People's Republic of China.
4
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
5
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China. ntwx0513@163.com.
6
Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, People's Republic of China. ntwx0513@163.com.
7
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China. ntsjh0513@163.com.
8
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China. ntsjh0513@163.com.

Abstract

Irreversible damage of cardiac function arisen from myocardial ischemia/reperfusion injury (MIRI) leads to an emerging challenge in the treatments of cardiac ischemic diseases. Molecular chaperone heat shock protein 70 (HSP70) attenuates heat-stimulated cell autophagy, apoptosis, and damage in the heart. Under specific conditions, autophagy may, directly or indirectly, induce cell death including necroptosis. Whether HSP70 inhibits cardiomyocyte necroptosis via suppressing autophagy during MIRI is unknown. In our study, HSP70 expression was opposite to necroptosis marker RIP1 and autophagy marker LC3A/B expression after myocardial ischemia/reperfusion (MIR) in vivo. Furthermore, in vitro primary rat cardiomyocytes mimicked MIRI by hypoxia/reoxygenation (H/R) treatment. Knockdown of HSP70 expression promoted cardiomyocyte autophagy and necroptosis following H/R treatment, while the increase tendency was downregulated by autophagy inhibitor 3-MA, showing that autophagy-induced necroptosis could be suppressed by HSP70. In summary, HSP70 downregulates cardiomyocyte necroptosis through suppressing autophagy during myocardial IR, revealing the novel protective mechanism of HSP70 and supplying a novel molecular target for the treatment of heart ischemic diseases.

KEYWORDS:

Autophagy; HSP70; Myocardial ischemia/reperfusion injury; Necroptosis

PMID:
27130675
DOI:
10.1007/s11626-016-0039-8
[Indexed for MEDLINE]

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