title: Involvement of miR-1 in the protective effect of hydrogen sulfide against cardiomyocyte apoptosis induced by ischemia/reperfusion.
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.
authors.affiliation: Department of Cardiothoracic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Fengyang Road #415, Shanghai, 200003, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Kang
authors.forename: Jiang
authors.initials: J
authors.lastname: Hong
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Zhinong
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006862:Hydrogen Sulfide / Q000378:metabolism*; D000860:Hypoxia; D035683:MicroRNAs / Q000235:genetics*; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000378:metabolism* / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: C542191:MIRN1 microRNA, rat; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D006862:Hydrogen Sulfide