title: Retinoid X receptor alpha participation in dexamethasone-induced rat bile acid coenzyme A-amino acid N-acyltransferase expression in septic liver.
abstract: To test the hypothesis that dexamethasone (Dex) treatment would restore rat hepatic bile acid coenzyme A-amino acid N-acyltransferase (rBAT) expression in septic rats after cecal ligation and puncture by increasing expression of retinoic acid X receptor alpha (RXRalpha), we assessed survival rate and bile and bile salt concentration in the Dex-treated septic group and compared these results with those for a nontreated septic group, a Dex-treated nonseptic group, and a sham group. Dexamethasone treatment (0.01 mg/kg) significantly improved the survival rate and increased the bile and bile salt concentration in the bile ducts of septic rats (P = <0.05). In our assessment of bile salt-related genes, during sepsis, there were decreases in protein and mRNA expression of rBAT and cholesterol 7 alpha-hydroxylase (CYP7A1). Treatment with Dex restored expression of rBAT and RXR[alpha] but not CYP7A1, bile salt export pump, or multidrug resistance associated protein 2 (MRP2). Na+-taurocholate cotransport protein and organic anion transporting polypeptide 1 were unchanged. In addition, treatment with Dex also restored the DNA-binding activity of RXR/farnesoid-X receptor to rBAT promoter containing inverted repeat 1 sequence. In an experiment to confirm our findings, RXR[alpha] siRNA was found to significantly block Dex-induced increases in expression of rBAT in hepatocytes taken from septic rats (P < 0.01).
  
  
  CONCLUSIONS
  Dex restored the expression of rBAT in septic rats by enhancing RXR[alpha], a process that might explain the mechanism underlying Dex's anticholestatic effect.
authors.affiliation: Department of Physiology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Bi-Chun
authors.initials: BC
authors.lastname: Chen
authors.forename: Kung-Kai
authors.initials: KK
authors.lastname: Kuo
authors.forename: Kung Yen-Hsu
authors.initials: KY
authors.lastname: Chen
authors.forename: Chia-Hsiung
authors.initials: CH
authors.lastname: Liu
authors.forename: Li-Yen
authors.initials: LY
authors.lastname: Tsai
authors.forename: Hseng-Kuang
authors.initials: HK
authors.lastname: Hsu
authors.forename: Chin
authors.initials: C
authors.lastname: Hsu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000217:Acyltransferases / Q000096:biosynthesis*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001646:Bile / Q000378:metabolism; D001652:Bile Ducts / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D029363:Organic Anion Transporters, Sodium-Dependent / Q000096:biosynthesis; D029362:Organic Anion Transporters, Sodium-Independent / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements; D047490:Retinoid X Receptor alpha / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism*; D027981:Symporters / Q000096:biosynthesis
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D000893:Anti-Inflammatory Agents; D029363:Organic Anion Transporters, Sodium-Dependent; D029362:Organic Anion Transporters, Sodium-Independent; D034741:RNA, Small Interfering; D047490:Retinoid X Receptor alpha; C421102:Slco1a1 protein, rat; D027981:Symporters; C071908:sodium-bile acid cotransporter; D003907:Dexamethasone; C532838:CYP7A1 protein, rat; D002790:Cholesterol 7-alpha-Hydroxylase; D000217:Acyltransferases; C026953:bile acid-CoA amino acid N-acyltransferase