Abstract
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.
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Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (81170232, 81100139, 81270419, 81200181 and 81270003); Second Military Medical University Doctoral Student Innovation Fund (2012); and the Science and Technology Commission of Shanghai Municipality (11JC1402402 and 12ZR1454600).
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Bo Kang, Jiang Hong and Jian Xiao are contributed equally to this work.
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Kang, B., Hong, J., Xiao, J. et al. Involvement of miR-1 in the protective effect of hydrogen sulfide against cardiomyocyte apoptosis induced by ischemia/reperfusion. Mol Biol Rep 41, 6845–6853 (2014). https://doi.org/10.1007/s11033-014-3570-2
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DOI: https://doi.org/10.1007/s11033-014-3570-2