RGD Reference Report - Peroxisome proliferator-activated receptor alpha (PPARalpha) activators induce hepatic farnesyl diphosphate synthase gene expression in rodents. - Rat Genome Database

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Peroxisome proliferator-activated receptor alpha (PPARalpha) activators induce hepatic farnesyl diphosphate synthase gene expression in rodents.

Authors: Le Jossic-Corcos, C  Pastori, GM  Duclos, S  Kawabe, Y  Pineau, T  Bournot, P 
Citation: Le Jossic-Corcos C, etal., J Steroid Biochem Mol Biol. 2004 Feb;88(2):203-11.
RGD ID: 2316299
Pubmed: PMID:15084352   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jsbmb.2003.11.011   (Journal Full-text)

Fibrates are hypolipidemic drugs that exert multiple effects on lipid metabolism by activating peroxisome proliferator-activated receptor alpha (PPARalpha) and modulating the expression of many target genes. In order to investigate the link between PPARalpha and cholesterol synthesis, we analysed the effect of fibrates on expression of the farnesyl diphosphate synthase (FPP synthase) gene, known to be regulated by sterol regulatory element-binding proteins (SREBPs), in conjunction with HMG-CoA reductase. In wild-type mice, both fenofibrate and WY 14,643 induced FPP synthase gene expression, an effect impaired in PPARalpha-null mice. A three-fold induction was observed in ciprofibrate-treated rat hepatocytes, in primary culture. This effect was decreased in presence of 5,6-dichlorobenzimidazole riboside (DRB) and cycloheximide (CHX), transcription and translation inhibitors, respectively. Acyl-CoA oxidase (AOX), a bona fide PPARalpha target gene, was induced by ciprofibrate but slower and more strongly than FPP synthase. In addition, induction of FPP synthase gene expression was abolished in the presence of 25-hydroxycholesterol (25-OH Chol). Thus, activation of PPARalpha by fibrates induced FPP synthase gene expression in both hepatocytes in culture and in mouse liver. This effect is likely to be dependent on cellular sterol level, possibly through SREBP-mediated transcriptional activation.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FdpsRatresponse to xenobiotic stimulus  IEP ciprofibrateRGD 

Objects Annotated

Genes (Rattus norvegicus)
Fdps  (farnesyl diphosphate synthase)


Additional Information