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.
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Acknowledgments
This work was supported in part by the National Natural Science Foundation of China (Nos. 81401365, 81373223, 81200918, 81172879), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Nantong science and technology project (MS12015056); Nantong University graduate scientific and technological innovation projects (No. YKS14010).
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Editor: Tetsuji Okamoto
Xiaojuan Liu, Chao Zhang, Xiang Wu and Jiahai Shi contributed equally to this work.
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Liu, X., Zhang, C., Zhang, C. et al. Heat shock protein 70 inhibits cardiomyocyte necroptosis through repressing autophagy in myocardial ischemia/reperfusion injury. In Vitro Cell.Dev.Biol.-Animal 52, 690–698 (2016). https://doi.org/10.1007/s11626-016-0039-8
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DOI: https://doi.org/10.1007/s11626-016-0039-8