Dissection of the multiple mechanisms of TNF-α-induced apoptosis in liver injury

被引:242
作者
Ding, WX [1 ]
Yin, XM [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA
关键词
apoptosis; mitochondria; Bcl-2 family proteins; TNF-alpha; reactive oxygen species; liver injury;
D O I
10.1111/j.1582-4934.2004.tb00469.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Tumor necrosis factor (TNF)-alpha-induced hepatocyte apoptosis is implicated in a wide range of liver diseases including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion liver injury, and fulminant hepatic failure. TNF-alpha exerts a variety of effects that are mediated mainly by TNF-receptor 1 (TNF-R1) in cell death. The activation of TNF-R1 leads to the activation of multiple apoptotic pathways involving the activation of the pro-death Bcl-2 family proteins, reactive oxygen species, C-Jun NH2-terminal kinase, cathepsin B, acidic sphingomyelinase and neutral sphingomyelinase. These pathways are closely interlinked and mainly act on mitochondria, which release the apoptogenic factors and other events, resulting in apoptosis. This article reviews the recent progress in the molecular mechanisms of TNF-alpha-induced apoptosis in hepatocytes, and discusses how these molecular findings are shaping our understanding of the pathogenesis of liver diseases and our strategy to develop novel therapeutics.
引用
收藏
页码:445 / 454
页数:10
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