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
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
ALDH3A1 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
2011
Lipid 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
2004
Genetically altered mice to evaluate glutathione homeostasis in health and disease
Dalton TP, Chen Y, Schneider SN, Nebert DW, Shertzer HG. Genetically altered mice to evaluate glutathione homeostasis in health and disease. Free Radical Biology And Medicine 2004, 37: 1511-1526. PMID: 15477003, DOI: 10.1016/j.freeradbiomed.2004.06.040.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRole of GSHGSH biosynthetic pathwayCell model systemBiosynthetic pathwayExogenous electrophilesGSH homeostasisCellular GSHHuman diseasesGlutathione homeostasisMouse modelGSH synthesisTripeptide glutathioneAntioxidant systemOxidative damageGenetic deficiencyModel systemOxidative stressHomeostasisSuch chemicalsGSHDisease processNonspecific effects