Bile acid regulation of hepatic physiology: IV. Bile acids and death receptors.
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.
Higuchi
Hajime
H
Division of Gastroenterology and Hepatology, Mayo Medical School, Clinic, and Foundation, Rochester, Minnesota 55905, USA.
Gores
Gregory J
GJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001647:Bile Acids and Salts / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000473:pathology* / Q000502:physiology*
D001647:Bile Acids and Salts