Hepatitis B virus X protein sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism.
Hepatitis B virus X protein sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism.
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发表时间：
2005-02
影响因子：
24.1
通讯作者：
Won-Ho Kim;F. Hong;B. Jaruga;Z. Zhang;S. Fan;T. Liang;B. Gao
中科院分区：
文献类型：
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作者：
Won-Ho Kim;F. Hong;B. Jaruga;Z. Zhang;S. Fan;T. Liang;B. Gao
有充分的文献记载表明，饮酒与肝炎病毒感染共同作用会加速肝损伤；然而，其潜在机制仍不清楚。在本文中，我们证明了来自过表达乙型肝炎病毒X蛋白（HBX）的转基因小鼠的原代肝细胞更容易受到乙醇和肿瘤坏死因子 -α诱导的凋亡性杀伤。与正常对照小鼠的肝细胞相比，乙醇和/或肿瘤坏死因子 -α处理导致来自HBX转基因小鼠的肝细胞中活性氧物质、线粒体通透性转换、细胞色素C释放、半胱天冬酶 -3活性以及多聚（ADP -核糖）聚合酶降解显著增加。阻断半胱天冬酶 -3活性可拮抗来自HBX转基因小鼠的原代肝细胞中乙醇和肿瘤坏死因子 -α诱导的凋亡。综上所述，我们的研究结果表明，HBX通过一种依赖半胱天冬酶 -3的机制使原代小鼠肝细胞对乙醇和肿瘤坏死因子 -α诱导的凋亡敏感，这可能部分解释了饮酒和乙型肝炎病毒感染对肝损伤的协同作用。
It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury; however the underlying mechanisms remain unknown. In this paper, we demonstrated that primary hepatocytes from transgenic mice overexpressing hepatitis B virus X protein (HBX) were more susceptible to ethanol- and TNF-alpha-induced apoptotic killing. Compared to normal control mouse hepatocytes, ethanol and/or TNF-alpha treatment led to a significant increase in reactive oxygen species, mitochondrial permeability transition, cytochrome C release, caspase-3 activity, and poly (ADP-ribose) polymerase degradation in hepatocytes from HBX transgenic mice. Blocking caspase-3 activity antagonized ethanol- and TNF-alpha-induced apoptosis in primary hepatocytes from HBX transgenic mice. Taken together, our findings suggest that HBX sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism, which may partly explain the synergistic effects of alcohol consumption and hepatitis B virus infection on liver injury.