title: Sustained repression and translocation of Ntcp and expression of Mrp4 for cholestasis after rat 90% partial hepatectomy.
abstract: OBJECTIVE
  To clarify the mechanism of persistent cholestasis after massive hepatectomy, the relationship between such cholestasis and the expression and localization of organic anion transporters for bile acids was examined in a rat model.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to 90% hepatectomy, and tissues were harvested at 0, 1, 3, and 7 days for microarray analysis, quantitative real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry to examine the expression of multidrug resistance protein 4 (Mrp4), bile salt export pump (Bsep), and sodium-dependent taurocholate cotransporting polypeptide (Ntcp).
  
  
  RESULTS
  Persistently elevated levels of serum bile acids were observed at days 3 and 7. RT-PCR and Western blotting indicated that the expression of Mrp4, a bile acid export pump located in the basolateral membrane, was increased at day 3. The expression of Ntcp, a transporter used to uptake bile acids from the sinusoids, was significantly decreased throughout the period. The levels of Bsep, an export pump localized to the canalicular membrane, were unchanged. Immunohistochemistry revealed the localization of Mrp4 and Bsep in the basolateral and canalicular membranes, respectively. On the other hand, at days 3 and 7, Ntcp was localized in the cytoplasm and was hardly detected in the basolateral membrane.
  
  
  CONCLUSIONS
  These results suggested that the sustained repression and translocation of Ntcp and the expression of Mrp4 at the basolateral membrane seem to be responsible for the high blood bile acids levels after massive hepatectomy.
authors.affiliation: Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miura
authors.forename: Norihisa
authors.initials: N
authors.lastname: Kimura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Naoki
authors.initials: N
authors.lastname: Nanashima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamana
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hakamada
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tsuchida
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D001693:Biological Transport, Active; D002779:Cholestasis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006498:Hepatectomy / Q000009:adverse effects*; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D059467:Transcriptome
chemical_list: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; C490548:Abcb11 protein, rat; C489542:Abcc4 protein, rat; C071908:sodium-bile acid cotransporter