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
2021
Oxidative stress and genotoxicity in 1,4-dioxane liver toxicity as evidenced in a mouse model of glutathione deficiency
Chen Y, Wang Y, Charkoftaki G, Orlicky DJ, Davidson E, Wan F, Ginsberg G, Thompson DC, Vasiliou V. Oxidative stress and genotoxicity in 1,4-dioxane liver toxicity as evidenced in a mouse model of glutathione deficiency. The Science Of The Total Environment 2021, 806: 150703. PMID: 34600989, PMCID: PMC8633123, DOI: 10.1016/j.scitotenv.2021.150703.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDioxanesDNA DamageFollow-Up StudiesGlutathioneLiverMiceMice, KnockoutOxidative StressConceptsOxidative stressLiver cytotoxicityGlutamate-cysteine ligase modifier subunitWild-type micePrimary target organRecent mouse studiesCYP2E1 inductionLiver toxicitySubchronic exposureNrf2 inductionOxidative DNA damageCancer riskMouse modelAnti-oxidative responseDNA damageTarget organsAnimal studiesLiver carcinogenicityRedox dysregulationEarly changesHealth CanadaNull miceMouse studiesNuclear factorCarcinogenic mechanisms
2020
Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer
Golla JP, Kandyliari A, Tan WY, Chen Y, Orlicky DJ, Thompson DC, Shah YM, Vasiliou V. Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer. Chemico-Biological Interactions 2020, 331: 109274. PMID: 33007288, PMCID: PMC9201852, DOI: 10.1016/j.cbi.2020.109274.Peer-Reviewed Original ResearchConceptsColorectal cancerColonic adenomasPresent preliminary studyMouse modelConsecutive daysLarge colonic adenomaPresence of adenomasApc mouse modelColon tumor growthMouse xenograft modelColon epithelial cellsFurther mechanistic studiesCancer mortalityKO miceLeading causeColorectal adenomasCRC developmentImmunohistochemical analysisXenograft modelTumor growthColorectal tumorigenesisAdenomasExpression scoreMale ApcMice
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 pathwayHepatic metabolic adaptation in a murine model of glutathione deficiency
Chen Y, Golla S, Garcia-Milian R, Thompson DC, Gonzalez FJ, Vasiliou V. Hepatic metabolic adaptation in a murine model of glutathione deficiency. Chemico-Biological Interactions 2019, 303: 1-6. PMID: 30794799, PMCID: PMC6743730, DOI: 10.1016/j.cbi.2019.02.015.Peer-Reviewed Original ResearchConceptsCellular non-protein thiolsMetabolic adaptationGlutamate-cysteine ligase modifier subunitNon-protein thiolsHepatic metabolic adaptationCellular redoxGlobal profilingGSH homeostasisModifier subunitLiver developmentBiochemical mechanismsMetabolic homeostasisAmino acidsGclm null miceDefense mechanismsEnvironmental insultsOxidative damageFatty liver developmentNull miceSpectrum of changesNucleic acidsMetabolic signaturesPivotal roleHomeostasisGlutathione deficiency
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 changesPhenotypeChronic Glutathione Depletion Confers Protection against Alcohol-induced Steatosis: Implication for Redox Activation of AMP-activated Protein Kinase Pathway
Chen Y, Singh S, Matsumoto A, Manna SK, Abdelmegeed MA, Golla S, Murphy RC, Dong H, Song BJ, Gonzalez FJ, Thompson DC, Vasiliou V. Chronic Glutathione Depletion Confers Protection against Alcohol-induced Steatosis: Implication for Redox Activation of AMP-activated Protein Kinase Pathway. Scientific Reports 2016, 6: 29743. PMID: 27403993, PMCID: PMC4940737, DOI: 10.1038/srep29743.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseaseGclm KO miceLiver steatosisKO miceAlcohol-induced liver steatosisFactor 2 (Nrf2) target genesEthanol-containing liquid dietOxidative stressGclm knockout mouseAlcohol-induced steatosisHepatic lipid profilesProtein kinase pathwayNew therapeutic strategiesNormal hepatic levelsLevels of glutathioneFatty acid oxidationKinase pathwayLiver diseaseLipid profileLiquid dietEthanol clearanceHepatic levelsTherapeutic strategiesKnockout miceSteatosisHeme oxygenase 1 protects ethanol-administered liver tissue in Aldh2 knockout mice
Matsumoto A, Thompson D, Chen Y, Vasiliou V, Kawamoto T, Ichiba M. Heme oxygenase 1 protects ethanol-administered liver tissue in Aldh2 knockout mice. Alcohol 2016, 52: 49-54. PMID: 27139237, DOI: 10.1016/j.alcohol.2016.02.004.Peer-Reviewed Original ResearchConceptsAldh2 knockout miceStress-related proteinsOxidative stress-related proteinsAlanine transaminaseAnti-oxidative proteinsKnockout miceHealthy individualsHepatic tumor necrosis factor alphaLiver tissueProtective factorsTumor necrosis factor alphaSerum alanine transaminaseRecent epidemiological studiesNecrosis factor alphaWild-type miceHeme oxygenase-1Cytochrome P450 2E1ALDH2 proteinProteinAldehyde dehydrogenase 2 geneHepatic malondialdehydeMechanistic explanationInflammatory cytokinesEthanol administrationMechanistic hypothesesALDH3A1 Plays a Functional Role in Maintenance of Corneal Epithelial Homeostasis
Koppaka V, Chen Y, Mehta G, Orlicky DJ, Thompson DC, Jester JV, Vasiliou V. ALDH3A1 Plays a Functional Role in Maintenance of Corneal Epithelial Homeostasis. PLOS ONE 2016, 11: e0146433. PMID: 26751691, PMCID: PMC4708999, DOI: 10.1371/journal.pone.0146433.Peer-Reviewed Original ResearchConceptsCorneal cell proliferationCorneal epithelial homeostasisCell proliferationALDH3A1 expressionEpithelial homeostasisHuman corneal epithelial cell lineDouble knockout miceAnti-proliferation effectCorneal epithelial cell lineCorneal epithelial proliferationAldehyde dehydrogenase 1A1Epithelial cell lineCorneal differentiation markersInner ocular tissuesInverse associationFunctional roleEpithelial proliferationKnockout miceP53 expressionCorneal epitheliumOcular tissuesMouse corneaCalcium concentrationMRNA levelsEpithelial differentiation
2015
ALDH1B1 links alcohol consumption and diabetes
Singh S, Chen Y, Matsumoto A, Orlicky DJ, Dong H, Thompson DC, Vasiliou V. ALDH1B1 links alcohol consumption and diabetes. Biochemical And Biophysical Research Communications 2015, 463: 768-773. PMID: 26086111, PMCID: PMC4517591, DOI: 10.1016/j.bbrc.2015.06.011.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DrinkingAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehyde Dehydrogenase, MitochondrialAnimalsBase SequenceDiabetes Mellitus, ExperimentalDNA PrimersEthanolGlucoseHomeostasisMiceMice, KnockoutReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionConceptsKO miceDevelopment of diabetesBlood glucose levelsBlood acetaldehyde levelsAldehyde dehydrogenase 1B1Knockout mouse lineGlucose levelsPharmacokinetic analysisMouse modelGlucose homeostasisKnockout miceAlcohol consumptionAcetaldehyde levelsAcetaldehyde metabolismGood healthMouse linesALDH2 proteinMiceALDH isozymesAlcohol sensitivityDiabetesStem cellsALDH1B1Physiological functionsMitochondrial enzymes
2013
Glutathione defense mechanism in liver injury: Insights from animal models
Chen Y, Dong H, Thompson DC, Shertzer HG, Nebert DW, Vasiliou V. Glutathione defense mechanism in liver injury: Insights from animal models. Food And Chemical Toxicology 2013, 60: 38-44. PMID: 23856494, PMCID: PMC3801188, DOI: 10.1016/j.fct.2013.07.008.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver injuryGlutamate-cysteine ligaseMouse modelLiver disease processTransgenic mouse modelCellular GSH concentrationGSH homeostasisLiver diseaseClinical stageHepatic insultLiver pathologyDisease processRate-limiting enzymeAnimal modelsHepatic GSHHepatic responseModifier subunitGenetic deficiencyInjuryPathophysiological functionsGSH deficitThiol antioxidantGSH concentrationMiceRole of GSH
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
Oral N-acetylcysteine rescues lethality of hepatocyte-specific Gclc-knockout mice, providing a model for hepatic cirrhosis
Chen Y, Johansson E, Yang Y, Miller ML, Shen D, Orlicky DJ, Shertzer HG, Vasiliou V, Nebert DW, Dalton TP. Oral N-acetylcysteine rescues lethality of hepatocyte-specific Gclc-knockout mice, providing a model for hepatic cirrhosis. Journal Of Hepatology 2010, 53: 1085-1094. PMID: 20810184, PMCID: PMC2970663, DOI: 10.1016/j.jhep.2010.05.028.Peer-Reviewed Original ResearchAcetylcysteineAdministration, OralAnimalsAntioxidantsBase SequenceCytokinesDisease Models, AnimalDNA PrimersGene Expression ProfilingGlutamate-Cysteine LigaseGlutathioneHepatocytesLiverLiver CirrhosisMiceMice, KnockoutMicroscopy, Electron, TransmissionMitochondria, LiverOxidative StressRNA, Messenger