MiR‐141 inhibition protects cardiomyocytes from anoxia/reoxygenation‐induced mitochondrial dysfunction

Abstract

BackgroundMitochondrial dysfunction plays an important role in ischemia/reperfusion (I/R) ‐induced myocardial injury. MicroRNAs are involved in myocardial injury after I/R. It has been reported that miR‐141 contributes to mitochondrial dysfunction in mice with diabetes. The aim of the present study is to dertmine whether the miR‐141 contributes to I/R‐induced myocardial injury and the underlying mechanism.MethodsHL‐1 cells were challenged with an anoxia/reoxygenation (A/R). miR‐141 expression in HL‐1 cells was detected by qRT‐PCR. Mitofusin‐2 (Mfn2) was assessed with Western blot. HL‐1 cellular oxygen consumption rate (OCR) was assessed with Seahorse XF24 analyzer.ResultsA/R challenge to HL‐1 cells increased miR‐141 expression and peaked at 12 hours after the reoxygenation. A/R challenge resulted in decreased mitochondrial membrane potential, OCR and ATP production of the cardiomyocytes, as well as increased LDH activity in the supernatant of the cardiomyocytes. The above changes were attenuated by transfection of the cardiomyocytes with miR‐141 inhibitor before the A/R. Overexpression of miR‐141 in the HL‐1 cell exaggerated the A/R‐induced mitochondrial dysfunction and cardiomyocyte injury. The A/R challenge to HL‐1 cells led to a decreased Mfn2 expression. Transfection of HL‐1 cells with miR‐141 mimics suppressed Mfn2 expression.ConclusionOur data indicate that miR‐141 is involved in A/R‐induced mitochondrial dysfunction by modulating Mfn2 protein expression.Support or Funding InformationThe study was supported by Natural Science Foundation of Jiangsu Province (BK20151332) and Natural Science Foundation of China (81370333).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.