GRP78 effectively protect hypoxia/reperfusion-induced myocardial apoptosis via promotion of the Nrf2/HO-1 signaling pathway.
Myocardial infarction is a major cause of death worldwide. Despite our understanding of the pathophysiology of myocardial infarction and the therapeutic options for treatment have improved substantially, acute myocardial infarction remains a leading cause of morbidity and mortality. Recent findings revealed that GRP78 could protect myocardial cells against ischemia reperfusion injury-induced apoptosis, but the exact function and molecular mechanism remains unclear. In this study, we aimed to explore the effects of GRP78 on hypoxia/reperfusion (H/R)-induced cardiomyocyte injury. Intriguingly, we first observed that GRP78 overexpression significantly protected myocytes from H/R-induced apoptosis. On mechanism, our work revealed that GRP78 protected myocardial cells from hypoxia/reperfusion-induced apoptosis via the activation of the Nrf2/HO-1 signaling pathway. We observed the enhanced expression of Nrf2/HO-1 in GRP78 overexpressed H9c2 cell, while GRP78 deficiency dramatically antagonized the expression of Nrf2/HO-1. Furthermore, we found that blocked the Nrf2/HO-1 signaling by the HO-1 inhibitor zinc protoporphyrin IX (Znpp) significantly retrieved H9c2 cells apoptosis that inhibited by GRP78 overexpression. Taken together, our findings revealed a new mechanism by which GRP78 alleviated H/R-induced cardiomyocyte apoptosis in H9c2 cells via the promotion of the Nrf2/HO-1 signaling pathway.
['Ji|Heyu|H|', 'Xiao|Feng|F|', 'Li|Suobei|S|', 'Wei|Ruan|R|', 'Yu|Fei|F|0000-0002-9036-2464', 'Xu|Junmei|J|']
D000818:Animals D017209:Apoptosis D015687:Cell Hypoxia D002460:Cell Line D002470:Cell Survival D000091342:Endoplasmic Reticulum Chaperone BiP D006321:Heart D006360:Heat-Shock Proteins D006419:Heme Oxygenase (Decyclizing) D006801:Humans D009203:Myocardial Infarction D032383:Myocytes, Cardiac D051267:NF-E2-Related Factor 2 D018384:Oxidative Stress D051381:Rats D015427:Reperfusion Injury
GRP78 apoptosis Nrf2 HO-1 myocardial hypoxia/reperfusion