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Am J Physiol Gastrointest Liver Physiol 284: G734-G738, 2003; doi:10.1152/ajpgi.00491.2002
0193-1857/03 $5.00
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Vol. 284, Issue 5, G734-G738, May 2003

THEME
Bile Acid Regulation of Hepatic Physiology
IV. Bile acids and death receptors

Hajime Higuchi and Gregory J. Gores

Division of Gastroenterology and Hepatology, Mayo Medical School, Clinic, and Foundation, Rochester, Minnesota 55905

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.

Fas; tumor necrosis factor-associated apoptosis-inducing ligand; Bid


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