Regulation of hepatocyte bile salt transporters during hepatic regeneration.
Bile formation is an essential liver-specific function, and the hepatic regeneration that occurs in response to hepatocellular injury is often associated with cholestasis. We have employed a partial hepatectomy model to examine the effect of hepatic regeneration on tissue-specific bile salt transporters and on Na(+)-K(+)-adenosinetriphosphatase (ATPase). Liver-specific sodium-dependent taurocholate uptake by basolateral plasma membrane vesicles was undetectable 24 h after hepatectomy. Basolateral membrane protein expression of the sodium-taurocholate cotransporter and gene expression of Ntcp were decreased by > 90% 24 h after partial hepatectomy. In vitro transcription assays demonstrated that Ntcp gene transcription was also markedly reduced. In contrast, hepatic Na(+)-K(+)-ATPase activity, protein expression, and gene expression were unaffected by partial hepatectomy. Similarly, protein and gene expression of the ectoATPase, a putative canalicular bile salt transporter, and canalicular ATP-dependent taurocholate uptake remained unchanged. Partial hepatectomy results in a marked reduction in the gene transcription and expression of the liver-specific Ntcp, as well as a decrease in protein expression and loss of transport activity. These changes provide a potential mechanism for the decrease in hepatocellular bile salt transport that is associated with hepatic regeneration.
Green
R M
RM
Section of Digestive and Liver Diseases, University of Illinois, Chicago College of Medicine 60612, USA.
Gollan
J L
JL
Hagenbuch
B
B
Meier
P J
PJ
Beier
D R
DR
D000251:Adenosine Triphosphatases / Q000096:biosynthesis*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D015342:DNA Probes; D007700:Kinetics; D008099:Liver / Q000502:physiology*; D008115:Liver Regeneration; D008297:Male; D029363:Organic Anion Transporters, Sodium-Dependent; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis*; D027981:Symporters; D013656:Taurocholic Acid / Q000378:metabolism*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D017931:DNA Primers; D015342:DNA Probes; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D000254:Sodium-Potassium-Exchanging ATPase