Bax interacts with the voltage-dependent anion channel and mediates ethanol-induced apoptosis in rat hepatocytes

Masayuki Adachi, Hajime Higuchi, Soichiro Miura, Toshifumi Azuma, Sayaka Inokuchi, Hidetsugu Saito, Shinzo Kato, Hiromasa Ishii

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89 Citations (Scopus)

Abstract

Acute ethanol exposure induces oxidative stress and apoptosis in primary rat hepatocytes. Previous data indicate that the mitochondrial permeability transition (MPT) is essential for ethanol-induced apoptosis. However, the mechanism by which ethanol induces the MPT remains unclear. In this study, we investigated the role of Bax, a proapoptotic Bcl-2 family protein, in acute ethanol-induced hepatocyte apoptosis. We found that Bax translocates from the cytosol to mitochondria before mitochondrial cytochrome c release. Bax translocation was oxidative stress dependent. Mitochondrial Bax formed a protein complex with the mitochondrial voltage-dependent anion channel (VDAC). Prevention of Bax-VDAC interactions by a microinjection of anti-VDAC antibody effectively prevented hepatocyte apoptosis by ethanol. In conclusion, these data suggest that Bax translocation from the cytosol to mitochondria leads to the subsequent formation of a Bax-VDAC complex that plays a crucial role in acute ethanol-induced hepatocyte apoptosis.

Original languageEnglish
Pages (from-to)G695-G705
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume287
Issue number3 50-3
DOIs
Publication statusPublished - 2004 Sep

Keywords

  • Alcoholic liver disease
  • Cytochrome c
  • Mitochondria
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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