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Retinoid X receptor alpha participation in dexamethasone-induced rat bile acid coenzyme A-amino acid N-acyltransferase expression in septic liver.

Authors: Chen, BC  Kuo, KK  Chen, KY  Liu, CH  Tsai, LY  Hsu, HK  Hsu, C 
Citation: Chen BC, etal., Shock. 2009 Aug;32(2):164-71.
Pubmed: (View Article at PubMed) PMID:19008781
DOI: Full-text: DOI:10.1097/SHK.0b013e318193e063

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). CONCLUSION: 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.

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CRRD Object Information
CRRD ID: 2317466
Created: 2010-04-06
Species: All species
Last Modified: 2010-04-06
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.