HEPATOCYTES IN THE BILE DUCT-LIGATED RAT EXPRESS BCL-2

Hepatocytes do not express Bcl-2, a repressor of apoptosis. In contras t, cholangiocytes, which are in direct contact with bile, do express B cl-2. Because cholestasis results in the retention of bile within hepa tocytes, we reasoned cholestasis may induce hepatocellular expression of Bcl-2. Thus our aim was to determine whether hepatocytes express Bc l-2 or alter expression of other Bcl-2 family members in cholestasis u sing the bile duct-ligated (BDL) rat as a model of cholestasis. De nov o Bcl-2 expression was observed in hepatocytes of BDL rats assessed by reverse transcriptase-polymerase chain reaction and immunoblot analys is. Immunohistochemistry demonstrated that Bcl-2 expression in hepatoc ytes was greater in periportal hepatocytes than pericentral hepatocyte s. Expression of Bcl-x (an antiapoptotic Bcl-2 family protein) was not altered by bile duct ligation, whereas expression of Bar (a proapopto tic Bcl-2 family protein) increased slightly as determined by Northern and Western blot analyses. Bcl-2-positive hepatocytes isolated from B DL rats were resistant to induction of apoptosis by 50 mu M glycocheno deoxycholate. Our results demonstrate, for the first time, expression of Bcl-2 by hepatocytes during cholestasis. We suggest that hepatocell ular expression of Bcl-2 during cholestasis is an adaptive phenomenon to resist apoptosis by toxic bile salts.