title: Taurocholate prevents the loss of intrahepatic bile ducts due to vagotomy in bile duct-ligated rats.
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 [(3)H]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.
authors.affiliation: Medical Physiology, Department of Internal Medicine, R & E, Scott & White Hospital, The Texas A&M University System Health Sciences Center, College of Medicine, and Central Texas Veterans Health Care System, Temple, Texas 76504, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Marzioni
authors.forename: Gene D
authors.initials: GD
authors.lastname: LeSage
authors.forename: Shannon
authors.initials: S
authors.lastname: Glaser
authors.forename: Tushar
authors.initials: T
authors.lastname: Patel
authors.forename: Carla
authors.initials: C
authors.lastname: Marienfeld
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Heather
authors.initials: H
authors.lastname: Francis
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
authors.forename: Laura
authors.initials: L
authors.lastname: Tadlock
authors.forename: Antonio
authors.initials: A
authors.lastname: Benedetti
authors.forename: Luca
authors.initials: L
authors.lastname: Marucci
authors.forename: Leonardo
authors.initials: L
authors.lastname: Baiocchi
authors.forename: Jo Lynne
authors.initials: JL
authors.lastname: Phinizy
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Alpini
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001647:Bile Acids and Salts / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D008026:Ligation; D008099:Liver / Q000294:innervation / Q000502:physiology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011916:Rats, Inbred F344; D013656:Taurocholic Acid / Q000494:pharmacology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000601:surgery; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D001647:Bile Acids and Salts; D020169:Caspases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D013656:Taurocholic Acid; D000077191:Wortmannin; C494920:Akt1 protein, rat