CYP1A1 Induction in the Colon by Serum: Involvement of the PPARα Pathway and Evidence for a New Specific Human PPREα Site
| Autor: | Francis Fouchier, P.H. Villard, Jean-Marc Pascussi, Marie-Josèphe Amiot, Eric Seree, Fabrice Barlesi, Yves Barra, Claire Dufour, Thi-Mai-Anh Dao, Serge Champion, Ayman Khalil, Martine Armand, Christian Ginies |
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| Přispěvatelé: | Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Nutriments Lipidiques et Prévention des Maladies Métaboliques, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Institut Montpelliérain de biologie (IMB), Université Montpellier 1 (UM1)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre régional de lutte contre le cancer-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sécurité et Qualité des Produits d'Origine Végétale (SQPOV), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance Publique - Ho'pitaux de Marseille (AP-HM 2001), Déposants HAL-Avignon, bibliothèque Universitaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université de la Méditerranée - Aix-Marseille 2, Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre régional de lutte contre le cancer-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 1 (UM1), Institut National de la Recherche Agronomique (INRA)-Avignon Université (AU) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Gastroenterology and Hepatology/Colon and Rectum
Serum Linoleic acid lcsh:Medicine Peroxisome proliferator-activated receptor Aromatic hydrocarbons 0302 clinical medicine Blood serum Gastrointestinal tract Electrophoretic mobility shift assay Gene expression polycyclic compounds heterocyclic compounds lcsh:Science Promoter Regions Genetic Caco-2 cells chemistry.chemical_classification 0303 health sciences Multidisciplinary biology santé humaine respiratory system Lipids 030220 oncology & carcinogenesis Signal transduction Research Article Signal Transduction Transcriptional Activation Gastroenterology and Hepatology/Gastrointestinal Cancers Colon Gastroenterology and Hepatology Response Elements 03 medical and health sciences BLOOD SERUM RT-PCR INDUCTION HEXANAL GASTROENTEROLOGIE Cytochrome P-450 CYP1A1 [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Humans PPAR alpha [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Binding site Fatty acids 030304 developmental biology Aldehydes Binding Sites lcsh:R Cytochrome P450 Monooxygenase Molecular biology In vitro chemistry Cancer research biology.protein lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, 2011, 6 (1), pp.e14629. ⟨10.1371/journal.pone.0014629⟩ Plos One 1 (6), e14629. (2011) PLoS ONE, Public Library of Science, 2011, 6 (1), pp.e14629. ⟨10.1371/journal.pone.0014629⟩ PLoS ONE, Vol 6, Iss 1, p e14629 (2011) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0014629⟩ |
| Popis: | International audience; Background: We previously showed that blood serum induced cytochrome P450 1A1 (CYP1A1) monooxygenase expression in vitro.Objective: Our purpose was (i) to identify the molecular mechanism involved and (ii) to characterize the inducer compound(s) in serum involved at least in part.Methods: Serum 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.Results: The 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 for human PPARα, an unreported PPRE property. A link was found between CYP1A1 inducibility and serum hydrophobic compounds. Characterization of sera showed that hexanal, a metabolite produced by peroxidation of linoleic acid, was involved in CYP1A1 induction by serum, possibly along with other serum entities.Conclusion: We demonstrate that serum induces CYP1A1 via the PPARα pathway and that hexanal is one of the serum inducers. The two PPRE sites within the CYP1A1 promoter are functional and one of them is specific for PPARα. |
| Databáze: | OpenAIRE |
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