6533b870fe1ef96bd12d0694
RESEARCH PRODUCT
Effect of oxidative stress on UDP-glucuronosyltransferases in rat astrocytes.
Alain MinnDaniela GradinaruJean-marie HeydelAnne-laure MinnYves Artursubject
MESH : Oxidative StressMESH : RNA MessengerAntioxidantTranscription Geneticmedicine.medical_treatmentToxicologyNAD(P)H:quinone oxidoreductase 1MESH: GlucuronosyltransferaseAntioxidantsSubstrate SpecificityRats Sprague-Dawley0302 clinical medicineMESH: NADPH-Ferrihemoprotein ReductaseMESH: GlucuronidesNAD(P)H Dehydrogenase (Quinone)MESH : CatalysisMESH: AnimalsMESH : NAD(P)H Dehydrogenase (Quinone)GlucuronosyltransferaseCells Culturedchemistry.chemical_classificationMESH : Cell Survival0303 health sciencesMESH : Substrate SpecificityMESH : Animals NewbornCytochrome P450 reductaseGeneral MedicineMESH: Cell SurvivalMESH: Pyridinium CompoundsMESH : AntioxidantsMESH: Cells CulturedOxidative phosphorylationGene Expression Regulation EnzymologicMESH : QuinonesMESH : Glucuronides03 medical and health sciencesRNA MessengerCell ShapeNADPH-Ferrihemoprotein ReductaseMESH : Oxidation-ReductionMESH : Pyridinium CompoundsMESH: NaphtholsMESH : GlucuronosyltransferaseMESH: AntioxidantsMESH: CatalysischemistryOxidative stressAstrocytesReactive Oxygen Species030217 neurology & neurosurgeryMESH: Oxidation-ReductionTime Factors[ SDV.AEN ] Life Sciences [q-bio]/Food and NutritionMESH : Reactive Oxygen SpeciesNADPH:cytochrome P450 reductasePyridinium CompoundsNaphtholsMESH: Rats Sprague-DawleyProtein oxidationmedicine.disease_causeMESH: Animals NewbornMESH: NAD(P)H Dehydrogenase (Quinone)Protein CarbonylationMESH : OxidantsMESH: OxidantsMelatoninMESH: MelatoninMESH: Oxidative StressMESH : MelatoninMESH : RatsMESH: Gene Expression Regulation EnzymologicQuinonesMESH: Reactive Oxygen SpeciesOxidantsBiochemistryMESH : Protein CarbonylationOxidation-ReductionUDP-glucuronosyltransferaseMESH : Time FactorsMESH: Protein CarbonylationMESH: RatsCell SurvivalMESH : NaphtholsBiologyCatalysisMESH: QuinonesMESH : Gene Expression Regulation EnzymologicGlucuronidesMESH : Cells CulturedmedicineAnimalsMESH: Cell Shape030304 developmental biologyMESH: RNA MessengerReactive oxygen speciesMESH: Transcription GeneticMESH: Time FactorsMESH : AstrocytesMESH : Transcription GeneticNAD(P)H Dehydrogenase (Quinone)MESH : Rats Sprague-DawleyRatsMESH: AstrocytesAnimals NewbornMESH : NADPH-Ferrihemoprotein ReductaseMESH: Substrate SpecificityMESH : AnimalsNAD+ kinaseMESH : Cell Shape[SDV.AEN]Life Sciences [q-bio]/Food and NutritionOxidative stressdescription
WOS:000309170300003; International audience; The present work reports data regarding effects of an induced oxidative stress on the mainly expressed isoforms of UDP-glucuronosyltransferases (UGTs) in the brain. UGT1A6 and UGT1A7 expression and enzymatic activities toward the 1-naphthol were analyzed in rat cultured astrocytes following the exposure for 48 h to redox-cycling xenobiotic compounds such as quinones and bipyridinium ions. The expression of NADPH:cytochrome P450 reductase and NAD(P)H:quinone oxidoreductase 1 (NQO1) was also investigated. Oxidative stress induced significant deleterious changes in astrocyte morphology, decreased cell viability and inhibited catalytic function of UGTs as a result of protein oxidation. Alternatively, in the surviving impaired astrocytes, oxidative conditions induced a significant overactivity and overexpression of xenobiotic detoxification enzymes, as adaptive response. These effects were significantly prevented by the presence of melatonin, suggesting its direct antioxidant action on reactive oxygen species, reflected further on the glucuronidation activity and transcriptional regulation of both UGT1A6 and UGT1A7. Results show that both catalytic properties of UGTs and the expression of UGT1A6, UGT1A7, NQO1 and NADPH:cytochrome P450 reductase in rat astrocytes are greatly influenced by the pro-oxidative environment. In conclusion, an experimental increase in oxidative cellular status could have both immediate and long term consequences on detoxification enzymatic system activity and expression.
year | journal | country | edition | language |
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2012-09-18 |