HIF-1α/BNIP3 signaling pathway-induced-autophagy plays protective role during myocardial ischemia-reperfusion injury

• Published in: Biomedicine & pharmacotherapy 2019-12, Vol.120, p.109464-109464, Article 109464
• Main Authors: Zhang, Yanan, Liu, Dawei, Hu, Haijuan, Zhang, Puqiang, Xie, Ruiqin, Cui, Wei
• Format: Article
• Language: English
• Subjects: Amino Acids, Dicarboxylic - pharmacology; Animals; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Beclin-1 - metabolism; BNIP3; Cell Hypoxia; Cell Line; HIF-1α; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Indazoles - pharmacology; Ischemia/reperfusion (I/R); Male; Membrane Proteins - metabolism; Microtubule-Associated Proteins - metabolism; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; Models, Animal; Myocardial Reperfusion Injury - chemically induced; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocytes, Cardiac; Oxygen–glucose deprivation/recovery (OGD/R) injury; Rats; Rats, Sprague-Dawley; Signal Transduction
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.109464

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. 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). 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. 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.