Bcl-2可保护小鼠免受抗Fas抗体诱导的致死性肝凋亡。

Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice.

作者信息

Lacronique V, Mignon A, Fabre M, Viollet B, Rouquet N, Molina T, Porteu A, Henrion A, Bouscary D, Varlet P, Joulin V, Kahn A

机构信息

Institut Cochin de Génétique Moléculaire, U 129 INSERM, Université René Descartes, Paris, France.

出版信息

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

DOI:10.1038/nm0196-80

PMID:8564847

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.

摘要

Fas是一种凋亡信号传导细胞表面抗原，已证明其在与特定配体或抗体结合后会触发细胞死亡。用抗Fas抗体处理小鼠会因大量细胞凋亡而导致暴发性肝衰竭。为了测试抗凋亡蛋白Bcl-2的假定保护作用，构建了转基因小鼠，使其在肝细胞中表达人bcl-2基因产物。在用抗Fas抗体处理的所有非转基因小鼠中，均观察到早期发生大量肝细胞凋亡并导致死亡。相比之下，转基因动物的肝细胞凋亡延迟且显著减少，存活率达93%。这些结果表明，Bcl-2能够保护细胞免受体内Fas介导的细胞毒性作用，对于预防人类病毒性肝炎所致的暴发性肝衰竭可能具有重要意义。