Cardioprotective effects of constitutively active MEK1 against H2O2-induced apoptosis and autophagy in cardiomyocytes via the ERK1/2 signaling pathway
Cardioprotective effects of constitutively active MEK1 against H2O2-induced apoptosis and autophagy in cardiomyocytes via the ERK1/2 signaling pathway
复制标题
组成型活性 MEK1 通过 ERK1/2 信号通路对 H2O2 诱导的心肌细胞凋亡和自噬的心脏保护作用
DOI：
10.1016/j.bbrc.2019.03.008
复制
发表时间：
2019-04-23
影响因子：
3.1
通讯作者：
Chen, Bang-Dang
中科院分区：
文献类型：
--
作者：
Sun, Ming-Hui;Chen, Xiao-Cui;Chen, Bang-Dang
氧化应激损伤是缺血再灌注（I/R）损伤的主要机制之一。细胞外信号调节激酶（ERK1/2）通路在急性心肌梗死期间的心脏保护中发挥重要作用。在本研究中，我们采用组成型活性MEK1基因（CaMEK）转染策略来研究CaMEK是否对过氧化氢（H2O2）诱导的新生大鼠心室心肌细胞（NCM）凋亡和自噬具有保护作用及其潜在机制。结果，CaMEK 减弱了 H2O2 诱导的 NCM 细胞凋亡和细胞毒性，具体表现为凋亡细胞和 Bax/Bcl-2 比值减少，增加了线粒体膜电位 (Delta psi m) 和细胞活力，并降低了乳酸脱氢酶 (LDH) 水平。进一 用 H2O2 刺激。相比之下，这些效应可以通过与 ERK1/2 抑制剂 PD98059 联合治疗来逆转。这些结果表明，CaMEK 通过 ERK1/2 途径在 NCM 中保护心肌细胞免受 H2O2 诱导的损伤和自噬中发挥重要作用。因此，CaMEK 的转染可能为 I/R 提供有希望的治疗策略。 (三) 2019 年作者。由爱思唯尔公司出版
Oxidative stress injury is one of the main mechanisms of ischemia-reperfusion (I/R) injury. The extracellular signal-regulated kinase (ERK1/2) pathway plays an important role in cardioprotective during acute myocardial infarction. In this study, we used constitutively active MEK1 gene (CaMEK) transfection strategy to investigate whether CaMEK provides a protective effect against apoptosis and autophagy induced by Hydrogen peroxide (H2O2) in neonatal rat cardiac ventricular cardiomyocytes (NCMs) and the underlying mechanisms. As a result, CaMEK attenuated H2O2-induced apoptosis and cytotoxicity in NCMs, evidenced by decreased apoptotic cells and the ratio of Bax/Bcl-2, increased the mitochondrial membrane potential (Delta psi m) and cell vitality and reduced the level of lactate dehydrogenase (LDH). Further studies revealed that CaMEK attenuated H2O2-induced autophagy, evidenced by the decreased LC3-II/LC3-(ratio and SQSTM1/p62 (p62) degradation. Furthermore, we demonstrated that CaMEK phosphorylated the ERK1/2 pathway-related proteins, ERK1/2, p70S6K and GSK3 beta, in NCMs with H2O2 stimulation. In contrast, these effects could be reversed by co-treatment with the ERK1/2 inhibitor, PD98059. These results suggest that CaMEK plays an important role in protecting cardiomyocytes against H2O2-induced injury and autophagy in NCMs via ERK1/2 pathway. Therefore, transfection of CaMEK may provide a hopeful therapeutic strategy for I/R. (C) 2019 The Authors. Published by Elsevier Inc.