title: Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice.
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.
authors.affiliation: Institut Cochin de Génétique Moléculaire, U 129 INSERM, Université René Descartes, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Lacronique
authors.forename: A
authors.initials: A
authors.lastname: Mignon
authors.forename: M
authors.initials: M
authors.lastname: Fabre
authors.forename: B
authors.initials: B
authors.lastname: Viollet
authors.forename: N
authors.initials: N
authors.lastname: Rouquet
authors.forename: T
authors.initials: T
authors.lastname: Molina
authors.forename: A
authors.initials: A
authors.lastname: Porteu
authors.forename: A
authors.initials: A
authors.lastname: Henrion
authors.forename: D
authors.initials: D
authors.lastname: Bouscary
authors.forename: P
authors.initials: P
authors.lastname: Varlet
authors.forename: V
authors.initials: V
authors.lastname: Joulin
authors.forename: A
authors.initials: A
authors.lastname: Kahn
mesh_terms: D000818:Animals; D000906:Antibodies / Q000633:toxicity*; D017209:Apoptosis / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D006501:Hepatic Encephalopathy / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
chemical_list: D000906:Antibodies; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D019204:GTP-Binding Proteins