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Binge alcohol promotes hypoxic liver injury via CYP2E1-HIF-1α-dependent apoptosis pathway in mice and humans

Monday, September 22, 2014 — Poster Session II

4:00 p.m. – 6:00 p.m.

FAES Academic Center



* FARE Award Winner


  • J.W. Yun
  • M.J. Son
  • M.A. Abdelmegeed
  • A. Banerjee
  • T.R. Morgan
  • S.H. Yoo
  • B.J. Song


This study was aimed to investigate the effects of acute binge alcohol on hypoxia-inducible factor-1α (HIF-1α)-mediated liver injury. Female wild-type mice were exposed to binge alcohol (n=3~4/group, three oral doses of 6 g/kg/each at 12-h intervals) and euthanized for collecting serum and liver tissues at different time points. Twenty six human blood and autopsied liver specimens were also analyzed. Binge alcohol promoted acute liver injury in mice with elevated levels of ethanol-inducible cytochrome P450-2E1 (CYP2E1) and hypoxia, both of which were co-localized in centrilobular areas. We observed positive correlations among elevated blood alcohol concentration (BAC), CYP2E1, and HIF-1α in mice and humans exposed to binge alcohol. The CYP2E1 protein levels and activities as well as HIF-1α levels showed significantly positive correlations with BACs in humans. However, no correlations were observed between the levels of alcohol dehydrogenase or aldehyde dehydrogenase and BAC or HIF-1α. Binge alcohol promoted protein nitration and hepatocyte apoptosis. Binge alcohol-induced HIF-1α activation and subsequent protein nitration or apoptosis were significantly alleviated in Cyp2e1-null mice, supporting the roles of CYP2E1 and HIF-1α in binge alcohol-mediated protein nitration and apoptosis. These results showed that binge alcohol promotes acute liver injury in mice and humans through a CYP2E1-HIF-1α-dependent apoptosis pathway.

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