MicroRNA-760-mediated low expression of DUSP1 impedes the protective effect of NaHS on myocardial ischemia-reperfusion injury.
Biochem Cell Biol
; 98(3): 378-385, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32160475
ABSTRACT
Myocardial ischemia-reperfusion injury (MIRI) is the leading cause of the poor prognosis for patients undergoing clinical cardiac surgery. Micro-RNAs are involved in MIRI; however, the effect of miR-760 on MIRI and the molecular mechanisms behind it have not yet been described. For our in-vivo experiments, 20 rats were randomly distributed between 2 groups (n = 10) the sham-treatment group and the ischemia-reperfusion (I/R) group. For our in-vitro experiments, H9C2 cells were subjected to hypoxia for 6 h, and then reoxygenated to establish an hypoxia-reoxygenation (H/R) model. High expression levels of of miR-760 were observed in the rats subjected to MIRI and the H9C2 cells subjected to H/R. Further, the levels of lactate dehydrogenase (LDH) and malonaldehyde (MDA) were increased, and the size of the myocardial infarct was notably greater in the rats subjected to MIRI, suggesting that miR-760 worsens the effects of MIRI. The inhibitory effects from NaHS on apoptosis were enhanced, as were the expression levels of cleaved caspase 3 and cleaved PARP in H9C2 cells exposed to H/R, and with low-expression levels of miR-760. TargetScan and dual luciferase reporter assays further confirmed the targeted relationship between dual-specificity protein phosphatase (DUSP1) and miR-760. Additionally, miR-760 overexpression and H/R treatment of H9C2 cells inhibited the expression of DUSP1, which further promoted apoptosis. Furthermore, DUSP1 enhanced the anti-apoptotic effects of NaHS in rats subjected to MIRI. Taken together, these findings suggest that miR-760 inhibits the protective effect of NaHS against MIRI.
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Base de dados:
MEDLINE
Assunto principal:
Sulfetos
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Traumatismo por Reperfusão Miocárdica
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Traumatismo por Reperfusão
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MicroRNAs
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Fosfatase 1 de Especificidade Dupla
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article