Involvement of miR-1 in the protective effect of hydrogen sulfide against cardiomyocyte apoptosis induced by ischemia/reperfusion
Involvement of miR-1 in the protective effect of hydrogen sulfide against cardiomyocyte apoptosis induced by ischemia/reperfusion
复制标题
miR-1参与硫化氢对缺血/再灌注诱导的心肌细胞凋亡的保护作用。
DOI：
10.1007/s11033-014-3570-2
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发表时间：
2014-10-01
影响因子：
2.8
通讯作者：
Wang, Zhinong
中科院分区：
文献类型：
--
作者：
Kang, Bo;Hong, Jiang;Wang, Zhinong
硫化氢（H2S）通过抗凋亡信号通路对心肌缺血/再灌注（IR）损伤的保护作用已被证实，但其潜在机制尚不清楚。近年来，miRNAs被认为是心肌损伤的重要介质，通过调控心肌肥厚相关基因而发挥作用。我们前期的研究发现，IR组microRNA-1（miR-1）表达较H2S预处理组有明显变化，提示miR-1具有心肌细胞特异性。在本研究中，我们试图了解miR-1是否通过调节凋亡相关基因参与H2S保护心肌细胞对抗IR诱导的凋亡。用H2S预处理和未预处理的新生大鼠心肌细胞进行缺氧/复氧（HR）损伤，用H2S预处理和未预处理的成年SD大鼠心肌进行IR损伤。结果发现，HR损伤可增加心肌细胞凋亡，上调miR-1的表达，下调Bcl-2的表达。H2S预处理可减轻HR损伤后心肌细胞凋亡和LDH释放，并增强细胞活力。HR上调miR-1表达，H2S预处理下调miR-1表达。而H2S预处理则上调Bcl-2的表达，HR则下调Bcl-2的表达。此外，miR-1模拟物以剂量依赖性方式下调Bcl-2蛋白。H2S也减弱了IR诱导的心肌细胞凋亡。MiR-1通过刺激Bcl-2调节H2S保护心肌细胞对抗IR诱导的凋亡。这些结果暗示miR-1是IR心肌中H2S的重要调节剂。
The protective effect of hydrogen sulfide (H2S) against myocardial ischemia/reperfusion (IR) injury via anti-apoptotic signaling is well established, but the underlying mechanism remains unclear. Recently, miRNAs have been identified as important mediators of myocardial injury by regulating apoptosis-related genes. It was found in our previous preliminary study that microRNA-1 (miR-1) expression underwent a significant change in IR group compared to H2S preconditioned group, indicating that miR-1 possessed myocyte-specific properties. In the present study, we intended to see whether miR-1 participated in H2S protection of cardiomyocytes against IR-induced apoptosis by regulating apoptosis-related genes. Cardiomyocytes of neonatal rats were subjected to hypoxia/reoxygenation (HR) injury with or without H2S preconditioning, while the myocardium of adult SD rats was subjected to IR with or without H2S preconditioning. It was found that HR injury increased apoptosis of cardiac myocytes, up-regulated the expression of miR-1, and down-regulated the expression of Bcl-2. H2S preconditioning attenuated cardiomyocyte apoptosis and LDH release, as well as enhanced cell viability following HR injury. MiR-1 was up-regulated by HR and down-regulated by H2S preconditioning. In contrast, Bcl-2 was down-regulated by HR and up-regulated by H2S preconditioning. In addition, Bcl-2 protein was down-regulated by the miR-1 mimic in a dose-dependent manner. H2S also attenuated IR-induced cardiomyocyte apoptosis in vivo. MiR-1 regulated H2S protection of cardiomyocytes against IR-induced apoptosis by stimulating Bcl-2. These results implicate miR-1 as an important regulator of H2S on the IR myocardium.