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CYP1A1 induction in the colon by serum: involvement of the PPARα pathway and evidence for a new specific human PPREα site Inra
Villard, P.H.; Barlesi, F.; Armand, M.; Dao, M.A.; Pascussi, J.M.; Fouchier, F.; Champion, S.; Dufour, C.; Ginies, C.; Ayman, K.; Amiot-Carlin, M.J.; Barra, Y.; Seree, É..
BackgroundWe previously showed that blood serum induced cytochrome P450 1A1 (CYP1A1) monooxygenase expression in vitro.ObjectiveOur purpose was (i) to identify the molecular mechanism involved and (ii) to characterize the inducer compound(s) in serum involved at least in part.MethodsSerum was fractionated on hydrophobic columns. PPARα involvement was demonstrated by gene reporter assays, DNA mutagenesis and EMSA. Gene expression was evaluated by qRT-PCR. Serum samples were analyzed using HS-SPME-GC-MS.ResultsThe inductive effect of serum did not depend on the AhR pathway and was enhanced by cotransfection of PPARα cDNA. Mutations in the PPAR response elements of the CYP1A1 gene promoter suppressed this effect. One of the PPRE sites appeared highly specific...
Tipo: Journal Article Palavras-chave: BLOOD SERUM; RT-PCR; INDUCTION; HEXANAL.
Ano: 2011 URL: http://www.prodinra.inra.fr/prodinra/pinra/doc.xsp?id=PROD201113910e75&uri=/notices/prodinra1/2011/05/
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PPARalpha transcriptionally induces AhR expression in Caco-2, but represses AhR pro-inflammatory effects Inra
Villard, P.H.; Caverni, S.; Baanannou, A.; Khalil, A.; Martin, P.G.; Penel, C.; Pineau, T.; Seree, É.; Barra, Y..
In this work we demonstrate that Caco-2 cell treatment with WY-14643 (a potent PPARα agonist) causes an increase in AhR expression. Luciferase assays and directed mutagenesis experiments showed that induction mainly occurred at transcriptional level and involved a PPRE site located within the AhR promoter. These results were further confirmed by the use of PPARα knockout mice in which AhR induction by WY14643 was abrogated. In addition to CYP1 regulation, AhR has been described as being involved in inflammation, so we also studied the effect of AhR regulation by PPARα on the expression of some inflammation target genes. 3-Methylcholanthrene (a potent AhR agonist) increased the expression (mRNA) of the major inflammatory targets IL-1β and MMP9. WY-14643...
Tipo: Journal Article Palavras-chave: INFLAMMATION; AHR; PPARALPHA; GUT; CACO-2.
Ano: 2007 URL: http://www.prodinra.inra.fr/prodinra/pinra/doc.xsp?id=PROD20079fb7485d&uri=/notices/prodinra1/2007/12/
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