Bcl-2 Protects From Lethal Hepatic Apoptosis Induced by an anti-Fas Antibody in Mice

Nat Med. 1996 Jan;2(1):80-6. doi: 10.1038/nm0196-80.

Abstract

Fas is an apoptosis-signalling cell surface antigen that has been shown to trigger cell death upon specific ligand or antibody binding. Treatment of mice with an anti-Fas antibody causes fulminant hepatic failure due to massive apoptosis. To test a putative protective effect of the anti-apoptotic Bcl-2 protein, transgenic mice were generated to express the human bcl-2 gene product in hepatocytes. Early onset of massive hepatic apoptosis leading to death was observed in all nontransgenic mice treated with an anti-Fas antibody. By contrast, hepatic apoptosis was delayed and dramatically reduced in transgenic animals, yielding a 93% survival rate. These results demonstrate that Bcl-2 is able to protect from in vivo Fas-mediated cytotoxicity, and could be of significance for preventing fulminant hepatic failure due to viral hepatitis in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / toxicity*
  • Apoptosis / physiology*
  • Blotting, Northern
  • Blotting, Western
  • GTP-Binding Proteins / biosynthesis
  • Hepatic Encephalopathy / pathology
  • Hepatic Encephalopathy / prevention & control*
  • Humans
  • Liver / metabolism
  • Liver / pathology*
  • Mice
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogenes*
  • fas Receptor / immunology
  • fas Receptor / physiology*

Substances

  • Antibodies
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor
  • GTP-Binding Proteins