6533b7ddfe1ef96bd12740d0
RESEARCH PRODUCT
Effects of typical inducers on olfactory xenobiotic-metabolizing enzyme, transporter, and transcription factor expression in rats.
Joëlle ChevalierYves ArturJean-marie HeydelAnne-marie Le BonMaud SigoillotNicolas Thiebaudsubject
MaleLIVERMESH : Transcription FactorsMESH: Microsomes Liver[ SDV.AEN ] Life Sciences [q-bio]/Food and NutritionPharmaceutical ScienceMESH : CytochromesMESH: Down-RegulationMESH: Membrane Transport ProteinsMESH : Down-RegulationCytosol0302 clinical medicineGlucocorticoid receptorMESH : Membrane Transport ProteinsMESH: CytosolMESH: Reverse Transcriptase Polymerase Chain ReactionGene expressionConstitutive androstane receptorMESH: Up-RegulationMESH: AnimalsReceptorMESH : Up-RegulationMESH: Cytochromes0303 health sciencesPregnane X receptorMESH : Metabolic Detoxication Phase IbiologyReverse Transcriptase Polymerase Chain ReactionMESH : RatsMESH : CytosolINDUCTIONMESH : Reverse Transcriptase Polymerase Chain ReactionMESH: Transcription FactorsUp-Regulation3. Good healthMESH : Microsomes LiverHYDROCARBON HYDROXYLASE-ACTIVITYmedicine.anatomical_structurePHASE-IBiochemistryMESH: Metabolic Detoxication Phase IIEnzyme InductionMicrosomes LiverMESH: Metabolic Detoxication Phase IMESH: XenobioticsMESH: Enzyme InductionMESH: RatsMESH : MaleDown-RegulationMESH : XenobioticsPHENOL SULFOTRANSFERASEMESH : Rats WistarXenobiotics03 medical and health sciencesOlfactory mucosaOlfactory MucosamedicineAnimalsRats WistarMESH: Olfactory MucosaTranscription factor030304 developmental biologyPharmacologyMESH : Olfactory MucosaIDENTIFICATIONRECEPTORMESH : Enzyme InductionMembrane Transport ProteinsMESH : Metabolic Detoxication Phase IIUDP-GLUCURONOSYLTRANSFERASEMESH: Rats WistarAryl hydrocarbon receptorORGANIC ANION TRANSPORTERMolecular biologyMetabolic Detoxication Phase IIMESH: MaleRatsNASAL-MUCOSAbiology.proteinCytochromesMetabolic Detoxication Phase IMESH : Animals[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition030217 neurology & neurosurgeryTranscription Factorsdescription
International audience; Several xenobiotic-metabolizing enzymes (XMEs) have been identified in the olfactory mucosa (OM) of mammals. However, the molecular mechanisms underlying the regulation of these enzymes have been little explored. In particular, information on the expression of the transcriptional factors in this tissue is quite limited. The aim of the present study was to examine the impact of five typical inducers, Aroclor 1254, 3-methylcholanthrene, dexamethasone, phenobarbital, and ethoxyquin, on the activities and mRNA expression of several XMEs in the OM and in the liver of rats. We also evaluated the effects of these treatments on the mRNA expression of transcription factors and transporters. On the whole, the intensities of the effects were lower in the OM than in the liver. Dexamethasone was found to be the most efficient treatment in the OM. Dexamethasone induced the transcription of several olfactory phase I, II, and III genes [such as cytochromes P450 2A3 and 3A9, UDP-glucuronosyltransferase (UGT) 2A1, and multidrug resistance-related protein type 1] and increased UGT activities. We observed that dexamethasone up-regulated sulfotransferase 1C1 expression in the OM but down-regulated it in the liver. Aroclor and ethoxyquin induced the gene expression of CYP1A and quinone reductase, respectively, in the OM. The transcription factors aryl hydrocarbon receptor, nuclear factor E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor α, pregnane X receptor, and glucocorticoid receptor were detected in the OM, but no constitutive androstane receptor expression was observed. Dexamethasone and Aroclor enhanced olfactory Nrf2 expression. These results demonstrate that olfactory XME can be modulated by chemicals and that the mechanisms involved in the regulation of these enzymes are tissue-specific.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-10-01 |