Glutathione depletion is associated with decreased Bcl-2 expression and increased apoptosis in cholangiocytes

ated with decreased Bcl-2 expression and increased apoptosis in cholangiocytes. Am. J. Physiol. 275 (Gastrointest. Liver Physiol. 38): G749–G757, 1998.—Cholangiocytes are the target of a group of liver diseases termed the cholangiopa-thies that include conditions characterized by periductal inflammation and cholangiocyte apoptosis. Because inflamma-tion is associated with oxidative stress, we developed the hypothesis that cholangiocytes exposed to oxidative stress will be depleted of endogenous cytoprotective molecules, leading to cholangiocyte apoptosis. To begin to test this hypothesis, we explored the relationships among glutathione (GSH) depletion, expression of Bcl-2 (a protooncogene that inhibits apoptosis), and apoptosis in a nonmalignant human cholangiocyte cell line. Monolayers of human bile duct epithe-lial cells, derived from normal liver and immortalized b