Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:MicroRNA-760-mediated low expression of DUSP1 impedes the protective effect of NaHS on myocardial ischemia-reperfusion injury. 3216 Apr 75

MicroRNAs (miRNAs) are involved in many pathological and biological processes, such as ischemia/reperfusion (I/R) injury by modulating gene expression. Increasing evidence indicates that miR-378a-3p might provide a potential cardioprotective effect against ischemic heart disease. Cell apoptosis is a crucial mechanism in I/R injury. As such, this study evaluated the protective effects and underlying mechanisms of action of miR-378a-3p on H9C2 cardiomyocyte apoptosis following I/R injury. We found that I/R-induced H9C2 cardiomyocytes exhibited a decrease in miR-378a-3p expression, while treatment with a miR-378a-3p mimic suppressed cell apoptosis, JNK1/2 activation, cleavage of PARP and caspase-3, and Bax/Bcl-2 ratio but increased DUSP1 expression, which subsequently inhibited JNK1/2 phosphorylation. TRIM55 was shown to be a target of miR-378a-3p and its downregulation inhibited the miR-378a-3p inhibitor-induced increase in cell apoptosis and JNK1/2 activation. TRIM55 inhibited DUSP1 protein expression through ubiquitination of DUSP1. Moreover, DUSP1 overexpression inhibited the TRIM55 overexpression-induced increase in cell apoptosis and JNK1/2 activation. The protective effect of miR-378a-3p was subsequently confirmed in a rat myocardial I/R model, as evidenced by a decrease in cardiomyocyte apoptosis of cardiomyocytes, TRIM55 expression, and JNK1/2 activation. Taken together, these results suggest that miR-378a-3p may protect against I/R-induced cardiomyocyte apoptosis via TRIM55/DUSP1/JNK signaling.
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PMID:miR-378a-3p inhibits ischemia/reperfusion-induced apoptosis in H9C2 cardiomyocytes by targeting TRIM55 via the DUSP1-JNK1/2 signaling pathway. 3246 95