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.

中文翻译：

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GRP78 通过促进 Nrf2/HO-1 信号通路有效保护缺氧/再灌注诱导的心肌细胞凋亡。

心肌梗塞是世界范围内的主要死亡原因。尽管我们对心肌梗塞的病理生理学和治疗方法的了解已大大改善，但急性心肌梗塞仍然是发病率和死亡率的主要原因。最近的研究结果表明，GRP78 可以保护心肌细胞免受缺血再灌注损伤诱导的细胞凋亡，但确切的功能和分子机制尚不清楚。在本研究中，我们旨在探讨 GRP78 对缺氧/再灌注 (H/R) 诱导的心肌细胞损伤的影响。有趣的是，我们首先观察到 GRP78 过表达显着保护心肌细胞免受 H/R 诱导的细胞凋亡。在机制上，我们的工作表明，GRP78 通过激活 Nrf2/HO-1 信号通路保护心肌细胞免受缺氧/再灌注诱导的细胞凋亡。我们观察到 Nrf2/HO-1 在 GRP78 过表达的 H9c2 细胞中的表达增强，而 GRP78 缺乏显着拮抗 Nrf2/HO-1 的表达。此外，我们发现通过 HO-1 抑制剂锌原卟啉 IX (Znpp) 阻断 Nrf2/HO-1 信号显着恢复了被 GRP78 过表达抑制的 H9c2 细胞凋亡。总之，我们的研究结果揭示了一种新机制，即 GRP78 通过促进 Nrf2/HO-1 信号通路减轻 H/R 诱导的 H9c2 细胞心肌细胞凋亡。而 GRP78 缺乏显着拮抗 Nrf2/HO-1 的表达。此外，我们发现通过 HO-1 抑制剂锌原卟啉 IX (Znpp) 阻断 Nrf2/HO-1 信号显着恢复了被 GRP78 过表达抑制的 H9c2 细胞凋亡。总之，我们的研究结果揭示了一种新机制，即 GRP78 通过促进 Nrf2/HO-1 信号通路减轻 H/R 诱导的 H9c2 细胞心肌细胞凋亡。而 GRP78 缺乏显着拮抗 Nrf2/HO-1 的表达。此外，我们发现通过 HO-1 抑制剂锌原卟啉 IX (Znpp) 阻断 Nrf2/HO-1 信号显着恢复了被 GRP78 过表达抑制的 H9c2 细胞凋亡。总之，我们的研究结果揭示了一种新机制，即 GRP78 通过促进 Nrf2/HO-1 信号通路减轻 H/R 诱导的 H9c2 细胞心肌细胞凋亡。