2024
Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression
Asantewaa G, Tuttle E, Ward N, Kang Y, Kim Y, Kavanagh M, Girnius N, Chen Y, Rodriguez K, Hecht F, Zocchi M, Smorodintsev-Schiller L, Scales T, Taylor K, Alimohammadi F, Duncan R, Sechrist Z, Agostini-Vulaj D, Schafer X, Chang H, Smith Z, O’Connor T, Whelan S, Selfors L, Crowdis J, Gray G, Bronson R, Brenner D, Rufini A, Dirksen R, Hezel A, Huber A, Munger J, Cravatt B, Vasiliou V, Cole C, DeNicola G, Harris I. Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression. Nature Communications 2024, 15: 6152. PMID: 39034312, PMCID: PMC11271484, DOI: 10.1038/s41467-024-50454-2.Peer-Reviewed Original ResearchConceptsGlutamate-cysteine ligase catalytic subunitLipid abundanceLipogenic enzyme expressionAbundance in vivoLipid productionCatalytic subunitRepress Nrf2Transcription factorsNrf2 repressionAdult tissuesSynthesis of GSHEnzyme expressionNon-redundantRedox bufferMouse liverLoss of GSHTriglyceride productionIn vivo modelsAbundanceGlutathione synthesisLiver balanceFat storesOxidative stressLipidDeletion
2022
Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues
Thompson B, Davidson EA, Chen Y, Orlicky DJ, Thompson DC, Vasiliou V. Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues. Chemico-Biological Interactions 2022, 355: 109804. PMID: 35123994, PMCID: PMC9136680, DOI: 10.1016/j.cbi.2022.109804.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsButhionine SulfoximineCell LineChemokine CCL7CytokinesDown-RegulationEpithelial CellsEpithelial-Mesenchymal TransitionEyeGlutamate-Cysteine LigaseImmunity, InnateLens, CrystallineLeukocytesMiceMice, Inbred C57BLMice, KnockoutOxidative StressReactive Oxygen SpeciesUp-RegulationConceptsPosterior capsule opacificationCytokine expressionKO miceImmune surveillanceOxidative stressLens epithelial cellsOcular structuresLens cellsDevelopment of PCOEpithelial cellsInnate immune cellsExpression of cytokinesEx vivo inductionOcular surface tissuesExpression of markersImmune response genesCON miceControl miceCapsule opacificationImmune cellsPostnatal dayΑ-SMAMouse modelOcular tissuesVivo induction
2019
Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis
Chen Y, Manna SK, Golla S, Krausz KW, Cai Y, Garcia-Milian R, Chakraborty T, Chakraborty J, Chatterjee R, Thompson DC, Gonzalez FJ, Vasiliou V. Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis. Free Radical Biology And Medicine 2019, 143: 127-139. PMID: 31351176, PMCID: PMC6848780, DOI: 10.1016/j.freeradbiomed.2019.07.025.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl Coenzyme AAlcohol DrinkingAMP-Activated Protein KinasesAnimalsEthanolFatty AcidsFatty LiverGlucuronic AcidGlutamate-Cysteine LigaseGlutamatesGlutathioneHomeostasisLipogenesisLiverMaleMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisOxidation-ReductionOxidative StressPentose Phosphate PathwayProtective AgentsTranscription, GeneticConceptsGlutamate-cysteine ligase modifier subunit geneProtein kinase pathwayAcetyl-CoA fluxMultiple cellular pathwaysAlcohol-induced steatosisCellular stressNucleotide biosynthesisLiver microarray analysisGlobal profilingSubunit geneCellular pathwaysMetabolic reprogrammingKinase pathwayMicroarray analysisMolecular mechanismsGSH poolCellular responsesMetabolic pathwaysLower GSHMolecular pathwaysMetabolic homeostasisAmino acidsDepletion of glutathioneCritical pathogenic eventGlucuronate pathway
2018
Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation
Lian G, Gnanaprakasam JR, Wang T, Wu R, Chen X, Liu L, Shen Y, Yang M, Yang J, Chen Y, Vasiliou V, Cassel TA, Green DR, Liu Y, Fan TW, Wang R. Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation. ELife 2018, 7: e36158. PMID: 30198844, PMCID: PMC6152796, DOI: 10.7554/elife.36158.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationDimethyl FumarateGlutamate-Cysteine LigaseGlutamineGlutathioneGlutathione DisulfideHomeostasisLymphocyte ActivationMice, Inbred C57BLOxidation-ReductionOxidative StressReactive Oxygen SpeciesReceptors, Antigen, T-CellTh17 CellsT-LymphocytesT-Lymphocytes, RegulatoryConceptsCell fateDe novo synthesisNovo synthesisCell differentiationT cell differentiationMurine T cell differentiationT cell fateGlutamate-cysteine ligaseLineage choiceRedox demandsGlutathione de novo synthesisRecycling pathwayInhibition of GSHRedox homeostasisGSH biosynthesisGlutamine catabolismRedox balanceModifier subunitEssential precursorIntracellular GSHEssential roleGlutathione disulfideDifferentiationGSH contentGSH
2017
Glutathione Primes T Cell Metabolism for Inflammation
Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brüstle A, Itsumi M, Jäger C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D. Glutathione Primes T Cell Metabolism for Inflammation. Immunity 2017, 46: 675-689. PMID: 28423341, DOI: 10.1016/j.immuni.2017.03.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEncephalomyelitis, Autoimmune, ExperimentalEnergy MetabolismGlutamate-Cysteine LigaseGlutamineGlutathioneGlycolysisImmunoblottingInflammationMice, Inbred C57BLMice, KnockoutNFATC Transcription FactorsProto-Oncogene Proteins c-mycReactive Oxygen SpeciesSignal TransductionT-LymphocytesTOR Serine-Threonine KinasesConceptsReactive oxygen speciesMYC transcription factorsConditional gene targetingT cell-specific ablationGlutamate-cysteine ligaseT cell metabolismRapamycin 1Catalytic subunitMetabolic integrationTranscription factorsGene targetingMetabolic reprogrammingBiosynthetic requirementsUnexpected roleExpression of NFATAntiviral defenseCysteine ligaseCell metabolismGSH pathwayMammalian targetGSH productionMurine TGSH deficiencyOxygen speciesCell effector functionsTranscriptomic analysis and plasma metabolomics in Aldh16a1-null mice reveals a potential role of ALDH16A1 in renal function
Charkoftaki G, Chen Y, Han M, Sandoval M, Yu X, Zhao H, Orlicky DJ, Thompson DC, Vasiliou V. Transcriptomic analysis and plasma metabolomics in Aldh16a1-null mice reveals a potential role of ALDH16A1 in renal function. Chemico-Biological Interactions 2017, 276: 15-22. PMID: 28254523, PMCID: PMC5725231, DOI: 10.1016/j.cbi.2017.02.013.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAnimalsDown-RegulationGene Expression ProfilingKidneyLipidsMetabolomicsMiceMice, Inbred C57BLMice, KnockoutMonocarboxylic Acid TransportersMultidrug Resistance-Associated ProteinsMutation, MissenseSequence Analysis, RNASodium-Phosphate Cotransporter Proteins, Type IUp-RegulationConceptsUric acid homeostasisPlasma metabolomicsElevated serum uric acid levelsSerum uric acid levelsDistal convoluted tubule cellsAcid homeostasisUric acid levelsZone 3 hepatocytesConvoluted tubule cellsSingle nucleotide variantsRenal functionKO miceLipid profileKnockout miceMissense single nucleotide variantsTubule cellsRNA-seq analysisKidneyMouse linesAcid levelsMicePotential roleLipid metabolic processMetabolomic analysisCellular lipids
2016
Corneal haze phenotype in Aldh3a1-null mice: In vivo confocal microscopy and tissue imaging mass spectrometry
Chen Y, Jester JV, Anderson DM, Marchitti SA, Schey KL, Thompson DC, Vasiliou V. Corneal haze phenotype in Aldh3a1-null mice: In vivo confocal microscopy and tissue imaging mass spectrometry. Chemico-Biological Interactions 2016, 276: 9-14. PMID: 28038895, DOI: 10.1016/j.cbi.2016.12.017.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAnimalsCorneaCorneal DiseasesCorneal StromaDiazepam Binding InhibitorDisease Models, AnimalDynamic Light ScatteringEpitheliumEpithelium, CornealHistonesLens, CrystallineLipidsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalPhenotypeSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationConceptsImaging mass spectrometryCorneal crystallinsNon-catalytic functionsAcyl-CoA binding proteinFirst genetic animal modelCellular transparencyCorneal epithelial homeostasisCorneal hazeEndogenous proteinsKO miceLipid localizationMixed genetic backgroundKnockout miceCorneal phenotypeEpithelial homeostasisProtein profilesWild-type corneasBinding proteinFunctional roleGenetic backgroundLens cataractMass spectrometryConfocal microscopyMolecular changesPhenotype
2012
Effect of chronic glutathione deficiency on the behavioral phenotype of Gclm(−/−) knockout mice
Chen Y, Curran CP, Nebert DW, Patel KV, Williams MT, Vorhees CV. Effect of chronic glutathione deficiency on the behavioral phenotype of Gclm(−/−) knockout mice. Neurotoxicology And Teratology 2012, 34: 450-457. PMID: 22580179, PMCID: PMC3404268, DOI: 10.1016/j.ntt.2012.04.009.Peer-Reviewed Original ResearchConceptsGlutamate-cysteine ligase modifier subunitMorris water mazeKO miceKnockout miceWater mazeOxidative stressChronic glutathione deficiencyPostnatal day 60Novel object recognitionWild-type littermatesTime of conceptionChronic GSH depletionChronic oxidative stressOpen-field activityKnockout mouse lineNormal spatial learningControl brain regionsAcoustic startleBehavioral abnormalitiesPostnatal lifeBrain regionsNeurodegenerative disordersDay 60Phenotyping testsMiceEffect of vitamin C deficiency during postnatal development on adult behavior: functional phenotype of Gulo(−/−) knockout mice
Chen Y, Curran C, Nebert D, Patel K, Williams M, Vorhees C. Effect of vitamin C deficiency during postnatal development on adult behavior: functional phenotype of Gulo(−/−) knockout mice. Genes Brain & Behavior 2012, 11: 269-277. PMID: 22296218, PMCID: PMC3325330, DOI: 10.1111/j.1601-183x.2011.00762.x.Peer-Reviewed Original ResearchConceptsGulo-/- miceBiosynthesis of ascorbateImportant cellular antioxidantAscorbate deficiencyL-gulono-γ-lactone oxidaseAmount of ascorbateGULO geneRate-limiting enzymeReactive oxygen speciesAerobic respirationAbnormal behavioral phenotypesMetabolic processesVitamin CCellular antioxidantsSupplemental vitamin CFunctional phenotypeOxygen speciesVitamin C deficiencyWild-type littermatesMild motor deficitsSpeciesBehavioral phenotypesPhenotypeDopamine agonistsMotor deficits
2011
Aldehyde dehydrogenases are regulators of hematopoietic stem cell numbers and B-cell development
Gasparetto M, Sekulovic S, Brocker C, Tang P, Zakaryan A, Xiang P, Kuchenbauer F, Wen M, Kasaian K, Witty MF, Rosten P, Chen Y, Imren S, Duester G, Thompson DC, Humphries RK, Vasiliou V, Smith C. Aldehyde dehydrogenases are regulators of hematopoietic stem cell numbers and B-cell development. Experimental Hematology 2011, 40: 318-329.e2. PMID: 22198153, DOI: 10.1016/j.exphem.2011.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehydesAnimalsAnimals, CongenicB-LymphocytesBone Marrow TransplantationCell CountCell CycleCell LineageCells, CulturedColony-Forming Units AssayDNA DamageEnzyme InductionGene Expression RegulationHematopoiesisHematopoietic Stem CellsLymphopeniaMiceMice, Inbred C57BLMice, KnockoutP38 Mitogen-Activated Protein KinasesRadiation ChimeraReactive Oxygen SpeciesRetinal DehydrogenaseSignal TransductionConceptsB cell developmentHematopoietic stem cellsReactive oxygen speciesMitogen-activated protein kinase activityP38 mitogen-activated protein kinase activityProtein kinase activityExcess reactive oxygen speciesOxygen speciesReactive aldehydesStem cell numbersHematopoietic stem cell numbersReactive oxygen species levelsEarly B cellsNumber of HSCsHSC biologyCell cycle distributionKinase activityOxygen species levelsAldh1a1 deficiencyGene expressionSpecies levelIntracellular signalingAldehyde dehydrogenasesDNA damageCell cyclingGlutathione-Deficient Mice Are Susceptible to TCDD-Induced Hepatocellular Toxicity but Resistant to Steatosis
Chen Y, Krishan M, Nebert DW, Shertzer HG. Glutathione-Deficient Mice Are Susceptible to TCDD-Induced Hepatocellular Toxicity but Resistant to Steatosis. Chemical Research In Toxicology 2011, 25: 94-100. PMID: 22082335, DOI: 10.1021/tx200242a.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAspartate AminotransferasesEnvironmental PollutantsFatty LiverFemaleGamma-GlutamyltransferaseGene Expression RegulationGlutamate-Cysteine LigaseGlutathioneLipid MetabolismLiverMiceMice, Inbred C57BLMice, KnockoutNon-alcoholic Fatty Liver DiseaseOligonucleotide Array Sequence AnalysisPolychlorinated DibenzodioxinsReverse Transcriptase Polymerase Chain ReactionConceptsTetrachlorodibenzo-p-dioxinGlutamic oxaloacetic transaminaseGlutamate-cysteine ligaseHepatocellular toxicityPlasma glutamic oxaloacetic transaminaseWild-type female miceImpaired lipid metabolismTissue GSH levelsTCDD-induced hepatotoxicityGlutathione-deficient miceΓ-glutamyl transferaseHepatocellular injuryWT miceHepatocellular damageLipid metabolism genesFemale miceWT littermatesTransgenic miceCDNA microarray expression analysisDe novo GSH biosynthesisOxaloacetic transaminaseLipid metabolismConsecutive daysSteatosisMiceLipid metabolism and body composition in Gclm(−/−) mice
Kendig EL, Chen Y, Krishan M, Johansson E, Schneider SN, Genter MB, Nebert DW, Shertzer HG. Lipid metabolism and body composition in Gclm(−/−) mice. Toxicology And Applied Pharmacology 2011, 257: 338-348. PMID: 21967773, PMCID: PMC3226854, DOI: 10.1016/j.taap.2011.09.017.Peer-Reviewed Original ResearchConceptsHigh-fat dietExcessive weight gainInsulin resistanceWeight gainFatty liverBasal metabolic rateGlutamate-cysteine ligase modifier subunit geneDecreased respiratory quotientExcess body weightIntestinal lipid absorptionHepatic oxidative stress responseDietary energy consumptionWild-type controlsGlucose intoleranceOxidative stress responseFat dietNormal dietRisk factorsBody compositionBody weightMetabolic rateDietary lipidsLipid absorptionMetabolic diseasesExperimental animals
2010
Aldehyde Dehydrogenase 1B1: Molecular Cloning and Characterization of a Novel Mitochondrial Acetaldehyde-Metabolizing Enzyme
Stagos D, Chen Y, Brocker C, Donald E, Jackson BC, Orlicky DJ, Thompson DC, Vasiliou V. Aldehyde Dehydrogenase 1B1: Molecular Cloning and Characterization of a Novel Mitochondrial Acetaldehyde-Metabolizing Enzyme. Drug Metabolism And Disposition 2010, 38: 1679-1687. PMID: 20616185, PMCID: PMC2957164, DOI: 10.1124/dmd.110.034678.Peer-Reviewed Original ResearchMeSH KeywordsAcetaldehydeAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehyde Dehydrogenase, MitochondrialAmino Acid SequenceAnimalsBaculoviridaeBlotting, WesternCell LineCloning, MolecularEthanolGenetic VectorsHumansImmunohistochemistryInsectaMaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaMolecular Sequence DataNADOrgan SpecificityOxidation-ReductionPlasmidsRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationGlutathione deficient C57BL/6J mice are not sensitized to ozone-induced lung injury
Johansson E, Wesselkamper SC, Shertzer HG, Leikauf GD, Dalton TP, Chen Y. Glutathione deficient C57BL/6J mice are not sensitized to ozone-induced lung injury. Biochemical And Biophysical Research Communications 2010, 396: 407-412. PMID: 20417186, PMCID: PMC2892220, DOI: 10.1016/j.bbrc.2010.04.105.Peer-Reviewed Original ResearchConceptsOzone-induced lung injuryGlutamate-cysteine ligase modifier subunitLung injuryLung hyperpermeabilityDegree of neutrophiliaBronchoalveolar lavage fluidWild-type miceInflammatory gene expressionPulmonary susceptibilityLavage fluidCompensatory augmentationKnockout miceTotal protein concentrationPpm ozoneMiceModifier subunitMRNA levelsAntioxidant defenseMember 2Antioxidant glutathioneMetallothionein-1GSH depletionHyperpermeabilityInjuryAntioxidant responseRedox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations, and Related Behaviors
Steullet P, Cabungcal JH, Kulak A, Kraftsik R, Chen Y, Dalton TP, Cuenod M, Q. K. Redox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations, and Related Behaviors. Journal Of Neuroscience 2010, 30: 2547-2558. PMID: 20164340, PMCID: PMC6634545, DOI: 10.1523/jneurosci.3857-09.2010.Peer-Reviewed Original Research8-Hydroxy-2'-DeoxyguanosineAdaptation, OcularAnalysis of VarianceAnimalsAnimals, NewbornBehavior, AnimalBiological ClocksCalbindin 2CalbindinsConditioning, ClassicalDeoxyguanosineElectric StimulationElectroencephalographyExcitatory Amino Acid AgonistsExploratory BehaviorFearFeeding BehaviorGene Expression RegulationGene Expression Regulation, DevelopmentalGlutamate-Cysteine LigaseGlutathioneHippocampusInterneuronsKainic AcidMaleMaze LearningMiceMice, Inbred C57BLMice, KnockoutNeural PathwaysOxidation-ReductionOxidative StressParvalbuminsPattern Recognition, VisualRewardS100 Calcium Binding Protein GSpatial Behavior
2009
Corneal aldehyde dehydrogenases: Multiple functions and novel nuclear localization
Stagos D, Chen Y, Cantore M, Jester JV, Vasiliou V. Corneal aldehyde dehydrogenases: Multiple functions and novel nuclear localization. Brain Research Bulletin 2009, 81: 211-218. PMID: 19720116, PMCID: PMC3025408, DOI: 10.1016/j.brainresbull.2009.08.017.Peer-Reviewed Original ResearchConceptsException of rabbitsCorneal epitheliumOcular tissuesMouse corneaProtective roleUVR exposureCorneaMessenger levelsNuclear presenceOxidative damageCorneal crystallinsSubstantial evidenceNovel nuclear localizationALDH3A1Rabbit keratocytesReactive aldehydesCell cycle regulationAntioxidant activityGene expressionALDHMost mammalsCycle regulationExogenous aldehydesNuclear localizationALDH1A1Early onset senescence occurs when fibroblasts lack the glutamate–cysteine ligase modifier subunit
Chen Y, Johansson E, Fan Y, Shertzer HG, Vasiliou V, Nebert DW, Dalton TP. Early onset senescence occurs when fibroblasts lack the glutamate–cysteine ligase modifier subunit. Free Radical Biology And Medicine 2009, 47: 410-418. PMID: 19427898, PMCID: PMC2773044, DOI: 10.1016/j.freeradbiomed.2009.05.003.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsBeta-GalactosidaseCell Culture TechniquesCell CycleCell Growth ProcessesCellular SenescenceCyclin-Dependent Kinase Inhibitor p21DNA DamageFemaleFetusFibroblastsFree Radical ScavengersGlutamate-Cysteine LigaseGlutathioneMiceMice, Inbred C57BLMice, KnockoutPregnancyProtein SubunitsReactive Oxygen SpeciesTumor Suppressor Protein p53ConceptsGlutamate-cysteine ligasePremature senescenceCellular redox environmentCellular antioxidant glutathionePrimary murine fibroblastsSenescence-associated beta-galactosidase activityCell cycle arrestInduction of p53Beta-galactosidase activityPrevents premature senescenceCatalytic subunitCellular senescenceGrowth arrestGlutamate cysteine ligase modifierModifier subunitP21 proteinPhysiological roleSenescenceDNA damageRedox environmentCycle arrestMurine fibroblastsGSH synthesisN-acetylcysteine increasesPrimary cellsCurcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit
Lavoie S, Chen Y, Dalton TP, Gysin R, Cuénod M, Steullet P, Q. K. Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit. Journal Of Neurochemistry 2009, 108: 1410-1422. PMID: 19183254, DOI: 10.1111/j.1471-4159.2009.05908.x.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntioxidantsAstrocytesCell SurvivalCells, CulturedCerebral CortexCurcuminDose-Response Relationship, DrugEmbryo, MammalianEnzyme InhibitorsGene ExpressionGlutamate-Cysteine LigaseGlutathioneHydroquinonesMiceMice, Inbred C57BLMice, KnockoutNeuronsProtein SubunitsQuercetinUp-RegulationConceptsGlutamate-cysteine ligaseGCL activityRate-limiting synthesizing enzymeRedox regulatorCatalytic subunitGSH levelsGene expressionCysteine ligaseGlutamate cysteine ligase modifierModifier subunitCell deathCell typesGSH synthesisEnzymeNeurodegenerative diseasesCultured neuronsGCLMSubunitsMRNA levelsSynthesizing enzymesGSHLower GSHAbility of curcuminExpressionLigase
2008
Knock-In Mouse Lines Expressing either Mitochondrial or Microsomal CYP1A1: Differing Responses to Dietary Benzo[a]pyrene as Proof of Principle
Dong H, Dalton TP, Miller ML, Chen Y, Uno S, Shi Z, Shertzer HG, Bansal S, Avadhani NG, Nebert DW. Knock-In Mouse Lines Expressing either Mitochondrial or Microsomal CYP1A1: Differing Responses to Dietary Benzo[a]pyrene as Proof of Principle. Molecular Pharmacology 2008, 75: 555-567. PMID: 19047483, PMCID: PMC2684908, DOI: 10.1124/mol.108.051888.Peer-Reviewed Original ResearchConceptsMitochondrial importCryptic targeting signalMitochondrial-targeting signalSignal recognition particleInner mitochondrial membraneDifferent substrate specificitiesMouse linesCYP1A1 proteinTargeting signalsRecognition particleCYP1A1 enzymeSubstrate specificityMitochondrial membraneEndoplasmic reticulumBaP toxicityPhysiological functionsTerminal processingProteinCytosolic peptidasesProof of principleMutationsEnzymeInducer propertiesCYP1B1 mRNAMicrosomal CYP1A1
2007
Oxidative and electrophilic stress induces multidrug resistance–associated protein transporters via the nuclear factor‐E2–related factor‐2 transcriptional pathway
Maher JM, Dieter MZ, Aleksunes LM, Slitt AL, Guo G, Tanaka Y, Scheffer GL, Chan JY, Manautou JE, Chen Y, Dalton TP, Yamamoto M, Klaassen CD. Oxidative and electrophilic stress induces multidrug resistance–associated protein transporters via the nuclear factor‐E2–related factor‐2 transcriptional pathway. Hepatology 2007, 46: 1597-1610. PMID: 17668877, DOI: 10.1002/hep.21831.Peer-Reviewed Original ResearchMeSH Keywords5' Flanking RegionAnimalsAntioxidantsButylated HydroxyanisoleCell Line, TumorFluorescent Antibody Technique, IndirectGene Expression RegulationGlutamate-Cysteine LigaseGlutathioneHepatocytesLiverMiceMice, Inbred C57BLMice, KnockoutMultidrug Resistance-Associated ProteinsNF-E2-Related Factor 2Oxidative StressPromoter Regions, GeneticPyrazinesReverse Transcriptase InhibitorsThionesThiophenesConceptsTranscriptional pathwaysBinding of Nrf2Nrf2 transcriptional pathwayNrf2 target genesMarked geneAdenosine triphosphate-dependent transportersChromatin immunoprecipitationElectrophilic stressNuclear Nrf2 levelsTarget genesRegulatory pathwaysCoordinated inductionPromoter regionProtein transportersMultidrug resistance-associated proteinNrf2-null miceResponse elementResistance-associated proteinHepa1c1c7 cellsProtein inductionFactor 2 (Nrf2) activatorQuinone oxidoreductase 1MRP transportersTransportersNrf2 levels