REGULATION OF HEPATOCYTE BILE-SALT TRANSPORTERS DURING HEPATIC REGENERATION

Bile formation is an essential liver-specific function, and the hepati c regeneration that occurs in response to hepatocellular injury is oft en associated with cholestasis. We have employed a partial hepatectomy model to examine the effect of hepatic regeneration on tissue-specifi c 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. Baso lateral membrane protein expression of the sodium-taurocholate cotrans porter and gene expression of Ntcp were decreased by >90% 24 h after p artial hepatectomy. In vitro transcription assays demonstrated that Nt cp gene transcription was also markedly reduced. In contrast, hepatic Na+-K+-ATPase activity, protein expression, and gene expression were u naffected by partial hepatectomy. Similarly, protein and gene expressi on of the ectoATPase, a putative canalicular bile salt transporter, an d canalicular ATP-dependent taurocholate uptake remained unchanged. Pa rtial hepatectomy results in a marked reduction in the gene transcript ion and expression of the liver-specific Ntcp, as well as a decrease i n protein expression and lass of transport activity. These changes pro vide a potential mechanism for the decrease in hepatocellular bile sal t transport that is associated with hepatic regeneration.