Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice.
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.
Lacronique
V
V
Institut Cochin de Génétique Moléculaire, U 129 INSERM, Université René Descartes, Paris, France.
Mignon
A
A
Fabre
M
M
Viollet
B
B
Rouquet
N
N
Molina
T
T
Porteu
A
A
Henrion
A
A
Bouscary
D
D
Varlet
P
P
Joulin
V
V
Kahn
A
A
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*
D000906:Antibodies; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D019204:GTP-Binding Proteins