MiR-486 regulates cardiomyocyte apoptosis by p53-mediated BCL-2 associated mitochondrial apoptotic pathwayReportar como inadecuado




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BMC Cardiovascular Disorders

, 17:119

Non-coronary artery cardiac disease

Abstract

BackgroundCardiomyocyte apoptosis is a common pathological manifestation that occurs in several heart diseases. This study aimed to explore the mechanism of microRNA-486 miR-486 in cardiomyocyte apoptosis by interfering with the p53-activated BCL-2 associated mitochondrial pathway.

MethodsmiR-486 mimics and inhibitors were transfected into the primary cardiomyocytes of suckling Sprague-Dawley rat pups, and H2O2 was used to induce apoptosis. Flow cytometry and TUNEL were both used to detect cardiomyocyte apoptosis, while the relative mRNA transcript and protein levels of miR-486, p53, Bbc3, BCL-2, and cleaved caspase-3 were detected using RT-PCR and western blot analysis, respectively.

ResultsmiR-486 overexpression significantly decreased the expressions of p53, Bbc3 and cleaved caspase-3 P < 0.05, and BCL-2 expression was significantly increased P < 0.05, which in turn caused a significant decrease in the rate of cardiomyocyte apoptosis P < 0.05. In contrast, miR-486 silencing resulted in an elevated rate of cardiomyocyte apoptosis P < 0.05.

ConclusionmiR-486 may regulate cardiomyocyte apoptosis via p53-mediated BCL-2 associated mitochondrial apoptotic pathway. Therefore, up-regulating miR-486 expression in cardiomyocytes can effectively reduce the activation of the BCL-2 associated mitochondrial apoptotic pathway, consequently protecting cardiomyocytes.

KeywordsCardiomyocyte Apoptosis miR-486 P53 BCL-2 pathway AbbreviationsANOVAAnalysis of variance

DAPI4′,6-diamidino-2-phenylindole

DCDown control

FBSFetal bovine serum

miRmicroRNA

MOIMultiplicity of infection

NCNegative control

PBSPhosphate buffered saline

PTENPhosphate and tension homology deleted on chromosome ten

RT-PCRReverse Transcription-Polymerase Chain Reaction

TBSTTris-buffered saline tween

TUNELTdT-mediated dUTP Nick-End labeling

UCUp control





Autor: Yuhan Sun - Qiang Su - Lang Li - Xiantao Wang - Yuanxi Lu - Jiabao Liang

Fuente: https://link.springer.com/







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