Carvedilol Protects Against the H2O2-induced Cell Damages in Rat Myoblasts by Regulating the Circ_NFIX/miR-125b-5p/TLR4 Signal Axis

This study was performed to investigate the molecular mechanism associated with circRNA nuclear factor IX (circ_NFIX) in carvedilol-mediated cardioprotection in H2O2-treated H9c2 cells. Flow cytometry was performed for the analysis of cell cycle and apoptosis. Cell proliferation was evaluated using colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide assay. Lactate dehydrogenase (LDH) activity was measured by LDH assay. The relative levels of circ_NFIX, microRNA-125b-5p (miR-125b-5p), and toll-like receptor 4 (TLR4) were determined by quantitative real-time polymerase chain reaction. Protein levels were examined by Western blot. The target interaction was proved by dual-luciferase reporter assay. H2O2-induced cell cycle arrest, proliferation repression, apoptosis, and LDH promotion in H9c2 cells were inhibited by carvedilol. The circ_NFIX level was reduced after carvedilol treatment in H2O2-treated H9c2 cells, and circ_NFIX overexpression inhibited the protective effects of carvedilol on H2O2-induced cell damages. Furthermore, circ_NFIX was validated to serve as a sponge of miR-125b-5p, and the inhibitory function of circ_NFIX in carvedilol-induced cardioprotection was achieved by sponging miR-125b-5p. Moreover, TLR4 acted as a target gene of miR-125b-5p and miR-125b-5p inhibitor upregulated the TLR4 expression to suppress the protective effects of carvedilol on H2O2-treated H9c2 cells. In addition, circ_NFIX regulated the TLR4 level by ex...
Source: Journal of Cardiovascular Pharmacology - Category: Cardiology Tags: Original Article Source Type: research