Manli Chen1,2, Qin Liu1, Lijian Chen1, Lei Zhang1, Xinqi Cheng1, Erwei Gu1. 1. Department of Anesthesiology, The first Affiliated Hospital of Anhui Medical University, Hefei, China. 2. Department of Anesthesiology, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou, China.
Abstract
BACKGROUND: Remifentanil postconditioning (RPC) confers robust cardioprotection against ischemia/reperfusion (I/R) injury. We recently determined that HDAC3 was involved in RPC-induced cardioprotection. However, the role of HDAC3 and its possible mechanisms in RPC-induced cardioprotection are unknown, which we aimed to evaluate in an in vitro hypoxia/reoxygenation (HR) model. METHODS: Myocardium I/R injury was established after HR with H9c2 cardiomyoblasts. Cell viability and apoptosis were evaluated usingCCK-8 and flow cytometry of HR-injured cardiomyoblasts treated with or without RPC. Furthermore, effects of RPC on HDAC3 protein and mRNA expression were evaluated with Western blot and quantitative real-time PCR analyses, whereas GSK-3β expression was measured with Western blot. RESULTS: RPC increased cell viability and reduced cell apoptosis (P < 0.05) in H9c2 cardiomyoblasts subjected to HR injury. In addition, RPC promoted the phosphorylation of GSK-3β at Ser9 site (P < 0.05) and suppressed the protein and mRNA expression of HDAC3 (P < 0.05). Lentiviral-transduced overexpression of HDAC3 had no significant effects on HR injury while attenuating the cardioprotective effects of RPC on cell viability and apoptosis (P < 0.05), GSK-3β phosphorylation (P < 0.05) in H9c2 cardiomyoblasts. CONCLUSIONS: RPC attenuates apoptosis in H9c2 cardiomyoblasts after HR injury by downregulating HDAC3-mediated phosphorylation of GSK-3β. Our findings suggest that HDAC3, and its cross talk function with GSK-3β, may be a promising target for myocardium I/R injury.
BACKGROUND:Remifentanil postconditioning (RPC) confers robust cardioprotection against ischemia/reperfusion (I/R) injury. We recently determined that HDAC3 was involved in RPC-induced cardioprotection. However, the role of HDAC3 and its possible mechanisms in RPC-induced cardioprotection are unknown, which we aimed to evaluate in an in vitro hypoxia/reoxygenation (HR) model. METHODS: Myocardium I/R injury was established after HR with H9c2 cardiomyoblasts. Cell viability and apoptosis were evaluated usingCCK-8 and flow cytometry of HR-injured cardiomyoblasts treated with or without RPC. Furthermore, effects of RPC on HDAC3 protein and mRNA expression were evaluated with Western blot and quantitative real-time PCR analyses, whereas GSK-3β expression was measured with Western blot. RESULTS: RPC increased cell viability and reduced cell apoptosis (P < 0.05) in H9c2 cardiomyoblasts subjected to HR injury. In addition, RPC promoted the phosphorylation of GSK-3β at Ser9 site (P < 0.05) and suppressed the protein and mRNA expression of HDAC3 (P < 0.05). Lentiviral-transduced overexpression of HDAC3 had no significant effects on HR injury while attenuating the cardioprotective effects of RPC on cell viability and apoptosis (P < 0.05), GSK-3β phosphorylation (P < 0.05) in H9c2 cardiomyoblasts. CONCLUSIONS: RPC attenuates apoptosis in H9c2 cardiomyoblasts after HR injury by downregulating HDAC3-mediated phosphorylation of GSK-3β. Our findings suggest that HDAC3, and its cross talk function with GSK-3β, may be a promising target for myocardium I/R injury.