Taurocholate prevents the loss of intrahepatic bile ducts due to vagotomy in bile duct
ligated rats.
Alpini, Marco Marzioni, Gene D. LeSage, Shannon Glaser, Tushar Patel, Carla
Marienfeld, Yoshiyuki Ueno, Heather Francis, Domenico Alvaro, Laura Tadlock,
Antonio Benedetti, Luca Marucci, Leonardo Baiocchi, Jo Lynne Phinizy, and
Gianfranco.
1Medical Physiology, 2Department of Internal Medicine, 3R & E, Scott &
White Hospital, The Texas A&M University System HSC, COM, and 8Central
Texas Veterans Health Care System, Temple, Texas 76504; 4Division of
Gastroenterology, Tohoku University School of Medicine, 1-1 Seiryo, Aobaku, Sendai,
Japan; 6Department of Gastroenterology, University of Ancona, Ancona; 5Division of
Gastroenterology, University of Rome, "La Sapienza," Rome; and the
7Department of Public Health, University of Rome Tor Vergata, Rome, Italy.
APStracts 10:0037G, 2003.
The aim 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 (PI3K) 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 PI3K. Bile acids
are important in modulating cholangiocyte proliferation in denervated livers.
Received 16 September 2002; accepted in final form 19 January 2003
APS Manuscript Number G398-2.
Article publication pending Am J Physiol Gastrointest Liver Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 27 February 2003