Involvement of MicroRNA-133a in the Protective Effect of Hydrogen Sulfide against Ischemia/Reperfusion-Induced Endoplasmic Reticulum Stress and Cardiomyocyte Apoptosis

• Published in: Pharmacology Vol. 103; no. 1-2; p. 1
• Main Authors: Ren, Lin, Wang, Qian, Chen, Yu, Ma, Yanzhuo, Wang, Dongmei
• Format: Journal Article
• Language: English
• Published: Switzerland 01.01.2019
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - genetics; Cardiotonic Agents - pharmacology; Cell Line; Disease Models, Animal; Endoplasmic Reticulum Stress - drug effects; Endoplasmic Reticulum Stress - genetics; Eukaryotic Initiation Factor-2 - metabolism; Heat-Shock Proteins - drug effects; Heat-Shock Proteins - metabolism; Hydrogen Sulfide - pharmacology; MicroRNAs - administration & dosage; MicroRNAs - biosynthesis; MicroRNAs - genetics; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - therapy; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - pathology; Rats; Rats, Sprague-Dawley; Transcription Factor CHOP - metabolism; Transfection; Hydrogen sulfide; Cardiomyocyte apoptosis; Ischemia/reperfusion; MicroRNA-133a; Endoplasmic reticulum stress
• ISSN: 1423-0313
• DOI: 10.1159/000492969

Myocardial ischemia/reperfusion (I/R) injury is a severe trauma that cells undergo and is associated with cardiomyocyte apoptosis. Recently, miRNAs have been demonstrated to play an important role in cardiovascular biology and disease. However, whether the miR-133a and ER stress play a role in hydrogen sulfide (H2S) protection of cardiomyocytes against I/R-induced apoptosis remains unclear. The neonatal cardiomyocytes were prepared to be treated with H2S or transfected with miR-133a activator or miR-133a inhibitor, either separately or in combination. Non-treated cardiomyocytes served as control. The ER stress biomarker GRP78, CHOP, and eIF2α expression levels were measured by Western blot. Cell apoptosis was assessed by flow cytometry after staining with the Annexin V- FITC. Proliferation was monitored by BrdU labeling, while cell migration and invasion were determined by Transwell assays. Pre-treatment of H2S and overexpression of miR-133a reversed I/R-induced ER stress and cardiomyocyte apoptosis in vitro and in vivo. The proliferation, migration, and invasion of cardiomyocytes were significantly increased by co-treatment with H2S and overexpression of miR-133a. These findings suggest the protective effect of miR-133a against I/R-induced ER stress and cardiomyocyte apoptosis and its enhancement of cell motility. Thus, cardioprotection by miR-133a overexpression provides a novel therapeutic approach to the treatment of ischemic heart diseases.