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

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.

Heat Shock Protein-70 Levels Are Associated With a State of Oxidative Damage in the Development of Bronchopulmonary Dysplasia

“…Some reports demonstrated that increased Hsp-70 expression in lungs protects alveolar epithelial cells against apoptosis and antagonizes the hyperoxia injury (14,17,18). Increasing evidence suggests that overexpression of Hsp-70 alleviates cell apoptosis via the mitogen-activated protein kinase (MAPK) signaling pathway, and exogenous extracellular Hsp-70 can prevent caspase-3 activation to inhibit cell apoptosis via Toll-like receptors and TRIF-nuclear factor kappa B pathway (14,(27)(28)(29). The results indicate that administration of recombinant human Hsp-70 with primary epithelial cells derived from TA significantly inhibited decreased respiratory epithelial cell apoptosis by hydrogen peroxideinduced oxidative stress; therefore, targeting Hsp-70 is possibly a good strategy to develop anti-oxidative therapeutics in patients with BPD.…”

Heat shock protein 70: A promising therapeutic target for myocardial ischemia–reperfusion injury

“…These changes facilitate the translocation of eEF2 into the nucleus and subsequently induce deformation and instability of the nucleus, thereby inducing cardiomyocyte apoptosis (C. Zhang, Liu, Zhang, et al, ). It was demonstrated that HSP70 bound to the C‐terminal fragment and the SUMO2/3‐ylation interaction motifs of eEF2, which subsequently contributed to inhibited phosphorylation and SUMOylation of eEF2, respectively (C. Zhang, Liu, Miao, et al, ). These functions of HSP70 inhibited the activation of eEF2 and suppressed the translocation of eEF2 into the nucleus, thus inhibiting eEF2‐induced cardiomyocyte apoptosis in I/R hearts (C. Zhang, Liu, Miao, et al, ).…”

Mesna ameliorates acute lung injury induced by intestinal ischemia–reperfusion in rats

“…Mine et al 60 added that HSP mRNA enhanced in leucocytes resulting from intestinal I–R. Hsp70 expression was also raised following I–R in rat kidney and heart 61 , 62 .…”