MicroRNA-488-3p is expressed highly in ethanol-induced cardiomyocytes and regulates mitochondrial function via target gene MFN1

Abstract

Objective To confirm ethanol-induced mitochondrial dysfunction in AC16 cardiomyocytes and the relationship with the ethanol concentration and duration. to investigate the nol. To study miR-488-3p promoted ethanol-induced mitochondrial dysfunction by regulating target gene MFN1. Methods The changes of mitochondrial morphology in cardiomyocytes were observed by fluorescence microscopy using mitotracker scanning. Mitochondrial membrane potential(MMP) and reactive oxygen species (ROS) contents were analyzed by flow cytometry. The expressions of miR-488-3p and MFN1 were detected by Real-time quantitative PCR or Western blot analysis, respectively.The interaction between miR-488-3p and MFN1 was explored by bioinformatics analysis and Luciferase reporter gene experiment. Results Ethanol intake damaged the mitochondrial morphology and function in AC16cardiomyocyte and there was the dependency upon ethanol concentration and duration. Mitochondrial dysfunctions in cells were manifested in abnormal mitochondrial morphology,decreasing MMPs, and increasing ROS contents. Ethanol intake upregulated expression levels of miR-488-3p,downregulated expression levels of MFN1 in AC16 cardiomyocytes and there was the dependency upon ethanol concentration and duration.Downregulation the expression level of miR-488-3p or upregulation expression levels of MFN1 after ethanol-induced cardiomyocytes, the damage to mitochondrial dysfunction can be reduced. miR-488-3p promoted ethanol-induced mitochondrial dysfunction by downregulating the expressions of MFN1. Conclusion 1.Ethanol can induce mitochondrial dysfunction in cardiomyocytes which is positively correlated with ethanol concentration and duration.2.The expression levels of miR-488-3p are decreased and the expression levels of MFN1 are recreased in AC16 cardiomyocytes after ethanol intake, which were positively correlated with ethanol concentration and duration.3. MFN1 is a direct target gene for miR-488-3p and together regulate mitochondrial function in AC16 cardiomyocytes. Key words: cardiomyocyte;alcoholic cardiomyopathy; mitochondrial dysfunction;mitochondrial membrane potential;reactive oxygen species;microRNA-488-3p; mitochondrial fusion protein 1