The interaction of Bcl-2 and Bax regulates apoptosis in biliary epithelial cells of rats with obstructive jaundice.
A complex molecular network controls cell homeostasis by inducing apoptosis or proliferation. The balance of Bcl-2 and Bax, members of a protein family, determines whether a cell will become immortal (Bcl-2) or will undergo apoptosis (Bax). To determine the role of Bcl-2 and Bax during proliferation of biliary epithelial cells (BEC) after bile duct ligation (BDL) and their regression after biliary decompression we induced hyperplasia of BEC by BDL in male rats. Regression of hyperplastic BEC by way of apoptosis was induced by biliary decompression through a Roux-en-Y biliodigestive anastomosis. To quantify apoptosis a modified TUNEL assay was used. Expression of Bcl-2 and Bax was visualized by immunohistochemistry and quantified stereologically. BEC increased from <1% to >20% after BDL; this increase was associated with overexpression of Bcl-2 in up to 30% of hyperplastic BEC. After biliodigestive anastomosis, apoptotic BEC increased from <0.1% to a peak of 5.4% after 1 day to reach baseline again 1 week after decompression. This was associated with de novo appearance of Bax. The interaction between Bcl-2 and Bax triggers apoptosis in BEC and acts as a cell rheostat in BEC hyperplasia and its involution after biliary decompression.
Stähelin
B J
BJ
Department of Internal Medicine, Inselspital, Berne, Switzerland.
Marti
U
U
Zimmermann
H
H
Reichen
J
J
D000713:Anastomosis, Roux-en-Y; D000818:Animals; D017209:Apoptosis; D001652:Bile Ducts / Q000601:surgery; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002779:Cholestasis / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D006965:Hyperplasia / Q000473:pathology; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008026:Ligation; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein