Suppression of Bim by microRNA-19a may protect cardiomyocytes against hypoxia-induced cell death via autophagy activation. (22nd August 2016)

• Record Type: Journal Article
• Authors: Gao, Yan-hua; Qian, Ju-ying; Chen, Zhang-wei; Fu, Ming-qiang; Xu, Jian-feng; Xia, Yan; Ding, Xue-feng; Yang, Xiang-dong; Cao, Yuan-yuan; Zou, Yun-zeng; Ren, Jun; Sun, Ai-jun; Ge, Jun-bo
• Is Part Of: Toxicology letters. Volume 257(2016)
• Page Start: 72
• Page End: 83
• Publication Date: 2016-08-22
• Subjects: 3′UTR 3′-untranslated region -- 3-MA 3-methyladenine -- Bim bcl-2 interacting mediator of cell death -- CAD coronary artery disease -- MO microvascular obstruction -- miRNAs microRNAs -- PCI percutaneous coronary intervention -- STEMI ST-segment elevation myocardial infarction -- LC3 microtubule-associated protein 1 light chain 3 -- mRFP monomeric red fluorescent protein -- GFP green fluorescent protein; MiR-19a -- Bim -- Cardiomyocytes -- Apoptosis -- Autophagy -- Hypoxia; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.05.019
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: We examined the function of miR-19a in cardiomyocyte apoptosis and the underlying mechanism;. MiR-19a overexpression ameliorated hypoxia-induced cell death by switching from apoptosis to autophagy;. The cytoprotection of miR-19a might be achieved through modulation of the specific target Bim. Abstract: Microvascular obstruction (MO), one of unfavorable complications of percutaneous coronary intervention (PCI), is responsible for the lost benefit of reperfusion therapy. Determination of microRNA-19a, a member of the miR-17-92 cluster, using quantitative real-time polymerase chain reaction (PCR) revealed notably down-regulated microRNA-19a, in myocardium with MO. Nonetheless, the role of miR-19a in MO and the underlying mechanism remains to be elucidated. To this end, an in vitro microembolization model in cardiomyocytes was used. Our data revealed that hypoxic exposure prompted cardiomyocyte apoptosis in a time-dependent manner accompanied by reduced miR-19a. miR-19a overexpression clearly ameliorated hypoxia-induced cell death (necrosis and apoptosis), at least in part, through switching on autophagy. Further dual-luciferase reporter assay and immunoblotting studies demonstrated that miR-19a-induced cytoprotection might be achieved in part through modulation of the specific target Bcl-2 interacting mediator of cell death, Bim, an apoptotic activator. Bim sufficiently interfered with miR-19a-induced LC3 conversion and increased cardiomyocyte apoptosis under hypoxia. Moreover, cardiomyocytes pretreated with 3-methyladenine conferred resistance to the cytoprotective effect of miR-19a and displayed notably increased TUNEL staining and caspase-3 activity. In conclusion, miR-19a protected cardiomyocytes against hypoxia-induced lethality at least in part via Bim suppression and subsequently autophagy activation.