Hepatocytes in the bile duct-ligated rat express Bcl-2.
Hepatocytes do not express Bcl-2, a repressor of apoptosis. In contrast, cholangiocytes, which are in direct contact with bile, do express Bcl-2. Because cholestasis results in the retention of bile within hepatocytes, we reasoned cholestasis may induce hepatocellular expression of Bcl-2. Thus our aim was to determine whether hepatocytes express Bcl-2 or alter expression of other Bcl-2 family members in cholestasis using the bile duct-ligated (BDL) rat as a model of cholestasis. De novo Bcl-2 expression was observed in hepatocytes of BDL rats assessed by reverse transcriptase-polymerase chain reaction and immunoblot analysis. Immunohistochemistry demonstrated that Bcl-2 expression in hepatocytes was greater in periportal hepatocytes than pericentral hepatocytes. Expression of Bcl-x (an antiapoptotic Bcl-2 family protein) was not altered by bile duct ligation, whereas expression of Bax (a proapoptotic Bcl-2 family protein) increased slightly as determined by Northern and Western blot analyses. Bcl-2-positive hepatocytes isolated from BDL rats were resistant to induction of apoptosis by 50 microM glycochenodeoxycholate. Our results demonstrate, for the first time, expression of Bcl-2 by hepatocytes during cholestasis. We suggest that hepatocellular expression of Bcl-2 during cholestasis is an adaptive phenomenon to resist apoptosis by toxic bile salts.
Kurosawa
H
H
Center for Basic Research in Digestive Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Que
F G
FG
Roberts
L R
LR
Fesmier
P J
PJ
Gores
G J
GJ
D000818:Animals; D017209:Apoptosis; D001652:Bile Ducts / Q000502:physiology*; D002478:Cells, Cultured; D002779:Cholestasis / Q000378:metabolism / Q000503:physiopathology*; D017931:DNA Primers; D008099:Liver / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D017931:DNA Primers; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein