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

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, Gianfranco Alpini

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)G837-G852
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume284
Issue number5 47-5
StatePublished - May 1 2003

Keywords

  • Apoptosis
  • Bile flow
  • Intrahepatic biliary epithelium
  • Proliferation
  • Secretin

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Marzioni, M., LeSage, G. D., Glaser, S., Patel, T., Marienfeld, C., Ueno, Y., Francis, H., Alvaro, D., Tadlock, L., Benedetti, A., Marucci, L., Baiocchi, L., Phinizy, J. L., & Alpini, G. (2003). Taurocholate prevents the loss of intrahepatic bile ducts due to vagotomy in bile duct-ligated rats. American Journal of Physiology - Gastrointestinal and Liver Physiology, 284(5 47-5), G837-G852.