Abstract

The pathogenesis of post-infarction ischemia-induced myocardial damage is related to hypoxia-mediated cardiomyocyte damage. In the present study, we explored the roles of ERK signaling pathway and endoplasmic reticulum (ER) stress in hypoxia-related cardiomyocyte damage. H9c2 cells were cultured under hypoxia condition in the presence of the ERK activator. Our data demonstrated that ER stress was significantly activated by hypoxia in cardiomyocyte, as evidenced by increased expression of PERK and CHOP through immunofluorescence. Interestingly, application of ERK activator significantly reduced hypoxia-mediated ER stress. Besides, ERK activation also sustained cardiomyocyte viability in the presence of hypoxia, as evidenced by decreased activities of caspase-3 and caspase-9. Altogether, our results demonstrated that ERK activation significantly promoted cardiomyocyte survival through inhibition of ER stress. This finding provides a novel insight into the molecular mechanism underlying hypoxia-mediated cardiomyocyte damage. Besides, our results also offer a potential target for the treatment and prevention of post-infarction ischemia-related myocardial damage.

摘要

梗死后缺血性心肌损伤的发病机制与缺氧介导的心肌细胞损伤有关。在本研究中，我们探讨了 ERK 信号通路和内质网 (ER) 应激在缺氧相关心肌细胞损伤中的作用。H9c2 细胞在 ERK 激活剂存在下在缺氧条件下培养。我们的数据表明，心肌细胞中的缺氧会显着激活 ER 应激，这可以通过免疫荧光增强 PERK 和 CHOP 的表达来证明。有趣的是，ERK 激活剂的应用显着降低了缺氧介导的 ER 应激。此外，ERK 激活还可以在缺氧的情况下维持心肌细胞的活力，这可以通过 caspase-3 和 caspase-9 的活性降低来证明。共，我们的研究结果表明，ERK 激活通过抑制 ER 应激显着促进心肌细胞存活。这一发现为了解缺氧介导的心肌细胞损伤的分子机制提供了新的见解。此外，我们的研究结果还为治疗和预防梗死后缺血相关的心肌损伤提供了潜在的靶点。