Taurocholate prevents the loss of intrahepatic bile ducts due to vagotomy in bile duct-ligated rats.
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.
Marzioni
Marco
M
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.
LeSage
Gene D
GD
Glaser
Shannon
S
Patel
Tushar
T
Marienfeld
Carla
C
Ueno
Yoshiyuki
Y
Francis
Heather
H
Alvaro
Domenico
D
Tadlock
Laura
L
Benedetti
Antonio
A
Marucci
Luca
L
Baiocchi
Leonardo
L
Phinizy
Jo Lynne
JL
Alpini
Gianfranco
G
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
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