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Biol Chem ; 404(6): 619-631, 2023 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-36780323

RESUMEN

MicroRNA (miR)-143-3p is a potential regulatory molecule in myocardial ischemia/reperfusion injury (MI/RI), wherein its expression and pathological effects remains controversial. Thus, a mouse MI/RI and cell hypoxia/reoxygenation (H/R) models were built for clarifying the miR-143-3p's role in MI/RI. Following myocardial ischemia for 30 min, mice underwent reperfusion for 3, 6, 12 and 24 h. It was found miR-143-3p increased in the ischemic heart tissue over time after reperfusion. Cardiomyocytes transfected with miR-143-3p were more susceptible to apoptosis. Mechanistically, miR-143-3p targeted B cell lymphoma 2 (bcl-2). And miR-143-3p inhibition reduced cardiomyocytes apoptosis upon H/R, whereas it was reversed by a specific bcl-2 inhibitor ABT-737. Of note, miR-143-3p inhibition upregulated bcl-2 with better mitochondrial membrane potential (Δψm), reduced cytoplasmic cytochrome c (cyto-c) and caspase proteins, and minimized infarction area in mice upon I/R. Collectively, inhibition of miR-143-3p might alleviate MI/RI via targeting bcl-2 to limit mitochondria-mediated apoptosis. To our knowledge, this study further clarifies the miR-143-3p's pathological role in the early stages of MI/RI, and inhibiting miR-143-3p could be an effective treatment for ischemic myocardial disease.


Asunto(s)
MicroARNs , Isquemia Miocárdica , Daño por Reperfusión Miocárdica , Daño por Reperfusión , Ratones , Animales , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , MicroARNs/metabolismo , Isquemia Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Apoptosis , Mitocondrias/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Daño por Reperfusión/metabolismo
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