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Heat shock protein 70 protects cardiomyocytes through suppressing SUMOylation and nucleus translocation of phosphorylated eukaryotic elongation factor 2 during myocardial ischemia and reperfusion

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Abstract

Myocardial ischemia and reperfusion (MIR) results in cardiomyocyte apoptosis with severe outcomes, which blocks cardiac tissue recovering from myocardial ischemia diseases. Heat shock protein 70 (HSP70) is one of protective molecule chaperones which could regulate the nucleus translocation of other proteins. In addition, eukaryotic elongation factor 2 (eEF2), which modulates protein translation process, is vital to the recovery of heart during MIR. However, the relationship between HSP70 and eEF2 and its effects on MIR are unclear. The expression and relationship between HSP70 and eEF2 is confirmed by western blot, immunoprecipitation in vitro using cardiomyocyte cell line H9c2 and in vivo rat MIR model. The further investigation was conducted in H9c2 cells with detection for cell-cycle and apoptosis. It is revealed that eEF2 interacted and be regulated by HSP70, which kept eEF2 as dephosphorylated status and preserved the function of eEF2 during MIR. In addition, HSP70 suppressed the nucleus translocation of phosphorylated eEF2, which inhibited cardiomyocyte apoptosis during myocardial reperfusion stage. Furthermore, HSP70 also interacted with C-terminal fragment of eEF2, which could reverse the nucleus translocation and cardiomyocyte apoptosis caused by N-terminal fragment of eEF2. HSP70 draw on advantage and avoid defect of MIR through regulating phosphorylation and nucleus translocation of eEF2.

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Acknowledgements

This work was supported by the National Basic Research Program of China (973 Program, No. 2012CB822104); National Natural Science Foundation of China (Nos. 81401365, 31500647, 81171140, 81471258, 31440037 and 31270802) The Natural Science Foundation of the Jiangsu Higher Education Institutions of China (14KJB180018); Nantong science and technology project (MS12015056, MS12015067); a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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    1. Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China

      Chao Zhang, Jingjing Li, Wanwan Guo & Xiang Wu

    2. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Xiaojuan Liu

    3. Laboratory Animals Centre, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, People’s Republic of China

      Jin Miao, Shengcun Wang & Liucheng Wu

    4. Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Daliang Yan

    5. Coinnovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, People’s Republic of China

      Aiguo Shen

    6. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Xiaojuan Liu & Aiguo Shen

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    Chao Zhang, Xiaojuan Liu, Xiang Wu and Aiguo Shen have contributed equally to this work.

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    Zhang, C., Liu, X., Miao, J. et al. Heat shock protein 70 protects cardiomyocytes through suppressing SUMOylation and nucleus translocation of phosphorylated eukaryotic elongation factor 2 during myocardial ischemia and reperfusion. Apoptosis 22, 608–625 (2017). https://doi.org/10.1007/s10495-017-1355-5

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