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Am J Physiol Gastrointest Liver Physiol 284: G837-G852, 2003. First published January 29, 2003; doi:10.1152/ajpgi.00398.2002
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Vol. 284, Issue 5, G837-G852, May 2003

Taurocholate prevents the loss of intrahepatic bile ducts due to vagotomy in bile duct-ligated rats

Marco Marzioni1, Gene D. LeSage2, Shannon Glaser3, Tushar Patel2, Carla Marienfeld2, Yoshiyuki Ueno4, Heather Francis3, Domenico Alvaro5, Laura Tadlock3, Antonio Benedetti6, Luca Marucci6, Leonardo Baiocchi7, Jo Lynne Phinizy3, and Gianfranco Alpini1,2,8

1 Medical Physiology, 2 Department of Internal Medicine, 3 R & E, Scott & White Hospital, The Texas A&M University System Health Sciences Center, College of Medicine, and 8 Central Texas Veterans Health Care System, Temple, Texas 76504; 4 Division of Gastroenterology, Tohoku University School of Medicine, 1 - 1 Seiryo, Aobaku, Sendai, Japan 980 - 8574; 6 Department of Gastroenterology, University of Ancona, Ancona 60100; 5 Division of Gastroenterology, University of Rome, "La Sapienza," Rome 00185; and the 7 Department of Public Health, University of Rome Tor Vergata, Rome, Italy 00185

The aim of this study was to determine whether taurocholate prevents vagotomy-induced cholangiocyte apoptosis. After bile duct ligation (BDL) + vagotomy, rats were fed taurocholate for 1 wk in the absence or presence of wortmannin. Caspase involvement was evaluated by measurement of caspase 8, 9, and 3 activities. Proliferation was determined by morphometry and PCNA immunoblots. Changes in phosphatidylinositol 3-kinase (PI3-kinase) activity were estimated by the expression of the phosphorylated Akt protein. Apically located Na+-dependent bile acid transporter (ABAT) expression and activity were evaluated by immunoblots and [3H]taurocholate uptake, respectively. Cholangiocyte apoptosis increased, whereas proliferation decreased in BDL + vagotomy rats. Taurocholate feeding prevented vagotomy effects on cholangiocyte functions, which were abolished by wortmannin. ABAT expression and activity as well as phosphorylated Akt protein expression were reduced by vagotomy but restored by taurocholate. The activities of caspase 8, 9, and 3 increased in BDL + vagotomy rats but were restored by taurocholate. The protective effect of taurocholate was associated with maintenance of ABAT activity, downregulation of caspase 8, 9, and 3, and activation of PI3-kinase. Bile acids are important in modulating cholangiocyte proliferation in denervated livers.

apoptosis; bile flow; intrahepatic biliary epithelium; proliferation; secretin


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