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

Research output: Contribution to journalArticle

84 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)

Fingerprint Dive into the research topics of 'Bax interacts with the voltage-dependent anion channel and mediates ethanol-induced apoptosis in rat hepatocytes'. Together they form a unique fingerprint.

  • Cite this