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
Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells
Franchina DG, Kurniawan H, Grusdat M, Binsfeld C, Guerra L, Bonetti L, Soriano-Baguet L, Ewen A, Kobayashi T, Farinelle S, Minafra AR, Vandamme N, Carpentier A, Borgmann FK, Jäger C, Chen Y, Kleinewietfeld M, Vasiliou V, Mittelbronn M, Hiller K, Lang PA, Brenner D. Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells. Nature Communications 2022, 13: 1789. PMID: 35379825, PMCID: PMC8980022, DOI: 10.1038/s41467-022-29426-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesGlutamate-Cysteine LigaseGlutathioneLymphoid TissueMiceOxidation-ReductionConceptsElectron transport chainMarginal zone B cellsMitochondrial electron transport chainGlutamate-cysteine ligaseCatalytic subunitRedox controlCell-specific ablationRedox balanceTransport chainMetabolic dependenciesCysteine ligaseProtein synthesisMetabolite succinateMTOR activationGlutathione synthesisATP levelsMetabolic propertiesB cellsMetabolic principlesMetabolic featuresDistinct metabolic propertiesMZBCellsActivationLigaseLipidomics and Redox Lipidomics Indicate Early Stage Alcohol‐Induced Liver Damage
Koelmel JP, Tan WY, Li Y, Bowden JA, Ahmadireskety A, Patt AC, Orlicky DJ, Mathé E, Kroeger NM, Thompson DC, Cochran JA, Golla JP, Kandyliari A, Chen Y, Charkoftaki G, Guingab‐Cagmat J, Tsugawa H, Arora A, Veselkov K, Kato S, Otoki Y, Nakagawa K, Yost RA, Garrett TJ, Vasiliou V. Lipidomics and Redox Lipidomics Indicate Early Stage Alcohol‐Induced Liver Damage. Hepatology Communications 2022, 6: 513-525. PMID: 34811964, PMCID: PMC8870008, DOI: 10.1002/hep4.1825.Peer-Reviewed Original ResearchConceptsAlcoholic fatty liver diseaseEthanol-treated miceFatty liver diseaseAlcohol consumption altersRegulation of triglycerideLiver lipidomeRegulation of phosphatidylcholineHepatic inflammationLiver biopsyLiver diseaseComprehensive time-course studyLiver damageHistological signsEarly biomarkersHistological markersMouse modelTime-course studyLiver tissueTriglyceridesHistological analysisEarly detectionLipid accumulationLiverMajor lipid classesDiet model
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 ResearchMeSH KeywordsAnimalsDisease Models, AnimalFatty LiverGlutamate-Cysteine LigaseGlutathioneHomeostasisLiverMetabolomicsMiceMice, KnockoutOxidation-ReductionConceptsCellular 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
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-CellT-LymphocytesT-Lymphocytes, RegulatoryTh17 CellsConceptsCell 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
2016
Chronic 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 ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsFatty Liver, AlcoholicGlutathioneMiceMice, KnockoutOxidation-ReductionSignal TransductionConceptsAlcoholic 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 miceSteatosis
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-IonizationRedox 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