ObjectiveTo investigate whether lipoxin A4 (LXA4) increases expression of heme oxygenase-1(HO-1) in cardiomyocytes, whether LXA4-induced HO-1 protects cardiomyocytes against hypoxia/reoxygenation (H/R) injury, and what are the mechanisms involved in the LXA4-induced HO-1 induction.MethodsRat cardiomyocytes were exposed to H/R injury with or without preincubation with LXA4 or HO-1 inhibitor ZnPP-IX or various signal molecule inhibitors. Expressions of HO-1 protein and mRNA were analyzed by using Western blot and RT-PCR respectively. Activity of nuclear factor E2-related factor 2 (Nrf2) binding to the HO-1 E1 enhancer was assessed by chromatin immunoprecipitation. Nrf2 binding to the HO-1 antioxidant responsive element (ARE) were measured by using electrophoretic mobility shift assay.ResultsPretreatment of the cells undergoing H/R lesion with LXA4 significantly reduced the lactate dehydrogenase and creatine kinase productions, increased the cell viability, and increased the expressions of HO-1 protein and mRNA and HO-1 promoter activity. HO-1 inhibition abolished the protective role of LXA4 on the cells undergoing H/R lesion. LXA4 increased p38 mitogen-activated protein kinase (p38 MAPK) activation, nuclear translocation of Nrf2, Nrf2 binding to the HO-1 ARE and E1 enhancer in cardiomyocytes with or without H/R exposure.ConclusionThe protection role of LXA4 against H/R injury of cardiomyocytes is related to upregulation of HO-1, via activation of p38 MAPK pathway and nuclear translocation of Nrf2 and Nrf2 binding to the HO-1 ARE and E1 enhancer, but not via activation of phosphatidyinositol-3-kinase or extracellular signal-regulated kinase pathway.
Background: CircRNA ACAP2 and miR-532 both promotes the apoptosis of cardiomyocytes, which contributes to myocardial infarction (MI). Therefore, ACAP2 and miR-532 may interact with each other to participate in MI.Method: Plasma samples from both MI patients (n=65) and healthy controls (n=65) were subjected to RNA extractions and RT-qPCR to analyze the expression of ACAP2, mature miR-532 and premature miR-532. Correlations among them were analyzed by Pearson's correlation coe cient. Expression of both mature miR-532 and premature miR-532 in cardiomyocytes with ACAP2 overexpression was analyzed by RT-qPCR to study the effects of ACAP2 overexpression on the maturation of miR-532. The role of ACAP2 and miR-532 in regulating the apoptosis of cardiomyocytes induced by hypoxia was analyzed by cell apoptosis assay.Results: In this study we found that ACAP2 and mature miR-532 were both upregulated in plasma from MI patients. ACAP2 and mature miR-532 were inversely correlated, while ACAP2 and premature miR-532 were not closely correlated. In cardiomyocytes, overexpression of ACAP2 decreased the expression of mature miR-532, but not premature miR-532. Cell apoptosis analysis showed that ACAP2 and miR-532 overexpression promoted the apoptosis of cardiomyocytes induced by hypoxia treatment. In addition, miR-532 inhibitor reduced the effects of ACAP2 overexpression. Conclusion: Therefore, ACAP2 is overexpressed in MI and may promote the maturation of miR-532 to induce the apoptosis of cardiomyocyte.
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