Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice
Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice
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DOI：
10.1038/nm0196-80
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发表时间：
1996-01-01
期刊：
影响因子：
82.9
通讯作者：
Kahn, A
中科院分区：
文献类型：
--
作者：
Lacronique, V;Mignon, A;Kahn, A
Fas是一种凋亡信号细胞表面抗原，已显示其在特异性配体或抗体结合时触发细胞死亡。用抗fas抗体治疗小鼠，由于大量细胞凋亡导致暴发性肝衰竭。为了测试抗凋亡Bcl-2蛋白的推定保护作用，产生转基因小鼠以在肝细胞中表达人bcl-2基因产物。在用抗Fas抗体处理的所有非转基因小鼠中观察到早期发生的导致死亡的大规模肝细胞凋亡。相比之下，转基因动物的肝细胞凋亡被延迟并显著减少，存活率为93%。这些结果表明，Eel-2能够防止体内Fas-mediated细胞毒性，并且对于预防人类病毒性肝炎引起的暴发性肝衰竭可能具有重要意义。
Fas is an apoptosis-signaling 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 Eel-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.