CYP1A1 Induction in the Colon by Serum: Involvement of the PPARα Pathway and Evidence for a New Specific Human PPREα Site

International audienceBackground: 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

Self-assembly and magnetic properties of a double-propeller octanuclear copper(II) complex with a meso-helicate-type metallacryptand core

An octanuclear copper(II) complex possessing a dimer-of-tetramers structure self-assembles from a binuclear oxamatocopper(II) metallacryptand of the meso-helicate type; its magnetic behaviour is consistent with its unique double-propeller molecular topology.Pardo Marín, Emilio José, [email protected] ; Julve Olcina, Miguel, [email protected] ; Lloret Pastor, Francisco, [email protected] ; Ruiz Garcia, Rafael, [email protected]

Resveratrol Increases Glucose Induced GLP-1 Secretion in Mice: A Mechanism which Contributes to the Glycemic Control

Resveratrol (RSV) is a potent anti-diabetic agent when used at high doses. However, the direct targets primarily responsible for the beneficial actions of RSV remain unclear. We used a formulation that increases oral bioavailability to assess the mechanisms involved in the glucoregulatory action of RSV in high-fat diet (HFD)-fed diabetic wild type mice. Administration of RSV for 5 weeks reduced the development of glucose intolerance, and increased portal vein concentrations of both Glucagon-like peptid-1 (GLP-1) and insulin, and intestinal content of active GLP-1. This was associated with increased levels of colonic proglucagon mRNA transcripts. RSV-mediated glucoregulation required a functional GLP-1 receptor (Glp1r) as neither glucose nor insulin levels were modulated in Glp1r-/- mice. Conversely, levels of active GLP-1 and control of glycemia were further improved when the Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin was co-administered with RSV. In addition, RSV treatment modified gut microbiota and decreased the inflammatory status of mice. Our data suggest that RSV exerts its actions in part through modulation of the enteroendocrine axis in vivo

Utilisation des organismes génétiquement modifiés dans la production de biocarburants

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

TR FRET et HTRF*Toolbox (une avancée dans le drug discovery )

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Apport de la thérapie génique dans le traitement de la maladie de Parkinson

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Nouvelle cible de PPAR alpha [Peroxisome Proliferator Activated Receptor] (le récepteur Ah)

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Validation et qualification de la sélection des cellules natural killer de grade clinique pour une immunothérapie antitumorale

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF