Yanan Zhang1, Dawei Liu1, Haijuan Hu1, Puqiang Zhang1, Ruiqin Xie1, Wei Cui2. 1. First Department of Cardiology, The Second Hospital of Hebei Medical University, Hebei Institute of Cardiovascular Research, Hebei, 050000, China. 2. First Department of Cardiology, The Second Hospital of Hebei Medical University, Hebei Institute of Cardiovascular Research, Hebei, 050000, China. Electronic address: cuiwei2h@163.com.
Abstract
OBJECTIVE: The study was established to inquire into the protective effect of the HIF-1α (Hypoxia-inducible factor-1α)/ BNIP3(Bcl-2/adenovirus E1B 19-kDa interacting protein) signal path-induced-autophagy during myocardial ischemia/ reperfusion (I/R) and oxygen-glucose deprivation/recovery (OGD/R) injury in heart-derived H9C2 cells as well as its potential underlying mechanism. METHODS: Immediate myocardial I/R in SD (Spraque Dawley) rats and cytotoxicity of OGD/R injury on H9C2 cells with and without inhibitors or agonists of HIF-1α and BNIP3 were evaluated. Expression of mitochondrial autophagic protein were detected by Western blot and immunofluorescence. And the mitochondrial autophagosome were detected using Transmission Electron Microscope (TEM). RESULTS: I/R and OGD/R injury increased the expression level of HIF-1α, activated the downstream BNIP3 and subsequently triggered mitochondria-dependent autophagy. Up-regulation the expression of HIF-1α and BNIP3 may promote the cardiac myocytes of SD rats of I/R injure and OGD/R injury-induced autophagy of H9C2 cells. Moreover, down-regulation the expression of HIF-1α or BNIP3-siRNA decreased H9C2 cells autophagy under OGD/R injury. CONCLUSIONS: Together, our studies indicated that HIF-1α synchronization regulate BNIP3 during OGD/R injury-induced autophagy in H9C2 cells, though BNIP3-induced autophagy acting as a survival mechanism.
OBJECTIVE: The study was established to inquire into the protective effect of the HIF-1α (Hypoxia-inducible factor-1α)/ BNIP3(Bcl-2/adenovirus E1B 19-kDa interacting protein) signal path-induced-autophagy during myocardial ischemia/ reperfusion (I/R) and oxygen-glucose deprivation/recovery (OGD/R) injury in heart-derived H9C2 cells as well as its potential underlying mechanism. METHODS: Immediate myocardial I/R in SD (Spraque Dawley) rats and cytotoxicity of OGD/R injury on H9C2 cells with and without inhibitors or agonists of HIF-1α and BNIP3 were evaluated. Expression of mitochondrial autophagic protein were detected by Western blot and immunofluorescence. And the mitochondrial autophagosome were detected using Transmission Electron Microscope (TEM). RESULTS: I/R and OGD/R injury increased the expression level of HIF-1α, activated the downstream BNIP3 and subsequently triggered mitochondria-dependent autophagy. Up-regulation the expression of HIF-1α and BNIP3 may promote the cardiac myocytes of SD rats of I/R injure and OGD/R injury-induced autophagy of H9C2 cells. Moreover, down-regulation the expression of HIF-1α or BNIP3-siRNA decreased H9C2 cells autophagy under OGD/R injury. CONCLUSIONS: Together, our studies indicated that HIF-1α synchronization regulate BNIP3 during OGD/R injury-induced autophagy in H9C2 cells, though BNIP3-induced autophagy acting as a survival mechanism.