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ASSA13-03-44 Inhibition of Autophagy Induced by Hypoxia Contributes to Apoptosis Via Upregulating of Bim and Caspase-3 by Downregulation of HIF-1 in Cardiac Myocytes
  1. Wang Luqiao,
  2. Huang Chahua,
  3. Wang Ling,
  4. Cheng Xiaoshu
  1. Department of Cardiovasology, the Second Affiliated Hospital of Nanchang University, Nanchang

Abstract

Objective This study aims to investigate the potential roles of autophagy induced by ischemia and tries to clarify the effects of HIF-1 in this process.

Methods We employed simulated hypoxia of neonatal rat ventricular myocytes as an in vitro model of ischemia injury to the heart. Cardiac myocytes were exposed to 2, 4, 8, 14, 24 h ischemia in hypoxic pouches. Cardiac myocytes were pretreated with 10mM 3-Methyladenine (3-MA) to inhibits autophagy. Western blot analysis was used to examine variation in the expression of LC3-II/I (a marker of autophagy), Bim, caspase-3 and HIF-1.

Results Our results demonstrated that the ratio of LC3-II/I was significantly increased when cardiac myocytes were exposed to hypoxia for 8h. Moreover, our results also demonstrated that significant a autophagy was reduced by pretreating with 3-Methyladenine (3-MA) in hypoxia, and the expression of Bim and caspase-3 was significantly increased. Western blot analysis showed that the expression of HIF-1 was increased significantly in hypoxia group and reduced in hypoxia+3-MA group.

Conclusions These results demonstrate that inhibition of autophagy induced by hypoxia constitutes a powerful and previously uncharacterized apopotosis in cardiac myocytes via upregulating the pro-apopototic protein Bim and caspase-3, which is regulated by HIF-1. Thus, manipulation of autophagy may represent a potential future therapeutic target to treat or prevent development of ischemic heart disease.

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