Bile acid regulation of hepatic physiology - IV. Bile acids and death receptors
Bile acid regulation of hepatic physiology - IV. Bile acids and death receptors
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DOI：
10.1152/ajpgi.00491.2002
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发表时间：
2003-05-01
影响因子：
4.5
通讯作者：
Gores, GJ
中科院分区：
文献类型：
--
作者：
Higuchi, H;Gores, GJ
有毒胆汁酸促进 Fas 和肿瘤坏死因子相关凋亡诱导配体 (TRAIL) 死亡受体寡聚化和激活。胆汁酸对死亡受体信号传导的调节是多因素的，包括将 Fas 运输到细胞表面、增强 TRAIL-R2/DR5 表达以及抑制 cFLIP（一种调节死亡受体功能的抗凋亡蛋白）的功能。由于胆汁酸相关死亡受体介导的细胞凋亡是胆汁淤积性肝细胞损伤的常见机制，因此抑制死亡受体及其级联可能有助于减轻胆汁淤积期间的肝损伤。
Toxic bile acids facilitate Fas and tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) death-receptor oligomerization and activation. Bile acid modulation of death-receptor signaling is multifactorial and includes trafficking of Fas to the cell surface, enhancing TRAIL-R2/DR5 expression, and suppression of function of cFLIP, an antiapoptotic protein modulating death-receptor function. Because bile acid-associated death receptor-mediated apoptosis is a common mechanism for cholestatic hepatocyte injury, inhibition of death receptors and their cascades may prove useful in attenuating liver injury during cholestasis.