RGD Reference Report - Role of retinoid-X receptor-alpha in the suppression of rat bile acid coenzyme A-amino acid N-acyltransferase in liver during sepsis. - Rat Genome Database

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Role of retinoid-X receptor-alpha in the suppression of rat bile acid coenzyme A-amino acid N-acyltransferase in liver during sepsis.

Authors: Chen, YH  Hong, IC  Kuo, KK  Hsu, HK  Hsu, C 
Citation: Chen YH, etal., Shock. 2007 Jul;28(1):65-70.
RGD ID: 1643106
Pubmed: PMID:17483744   (View Abstract at PubMed)
DOI: DOI:10.1097/shk.0b013e31802ec5d2   (Journal Full-text)

Sepsis causes intrahepatic cholestasis and leads to hepatic failure. However, the pathophysiology of hepatic events is unclear. Expression of rat hepatic bile acid coenzyme A-amino acid N-acyltransferase (rBAT), a major enzyme for the conjugation of bile acids, is significantly decreased during sepsis. rBAT transcriptional regulation is mainly by a heterodimer of farnesoid-X receptor (FXR) and retinoid-X receptor-alpha (RXR-alpha) via the inverted repeat 1 sequence. During sepsis, nuclear receptors and translocation of RXR-alpha from cytosol to nucleus decrease. The purpose of this study was to further clarify the mechanisms of RXR-alpha-mediated rBAT regulation during polymicrobial sepsis and with dexamethasone treatment. Polymicrobial sepsis was induced in rats by cecal ligation and puncture (CLP). Liver tissues obtained 3, 6, 9, and 18 h after CLP were studied, and hepatocytes were isolated from rats with sepsis. Post-CLP decreases were observed in mRNA levels of rBAT (6 h), protein levels of rBAT (6 h), RXR-alpha (6 h), and FXR (9 h). DNA binding activity of FXR/RXR significantly decreased at 6 h after CLP. Dexamethasone reversed sepsis-inhibited RXR-alpha expression and the binding activity of FXR/RXR to rBAT DNA as well as rBAT protein expression. The results suggest that suppression of rBAT occurs at the transcriptional level, and the decrease in RXR-alpha by septic insult may play a critical role in rBAT suppression at the early stage of polymicrobial sepsis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RXRAHumanSepsis  ISORxra (Rattus norvegicus)protein:decreased expression:liverRGD 
RxraRatSepsis  IEP protein:decreased expression:liverRGD 
RxraMouseSepsis  ISORxra (Rattus norvegicus)protein:decreased expression:liverRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RxraRatresponse to glucocorticoid  IEP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RxraRatdouble-stranded DNA binding contributes_toIDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rxra  (retinoid X receptor alpha)

Genes (Mus musculus)
Rxra  (retinoid X receptor alpha)

Genes (Homo sapiens)
RXRA  (retinoid X receptor alpha)


Additional Information