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 and Transsulfuration in Alcohol-Associated Tissue Injury and Carcinogenesis
Chen Y, Han M, Matsumoto A, Wang Y, Thompson DC, Vasiliou V. Glutathione and Transsulfuration in Alcohol-Associated Tissue Injury and Carcinogenesis. Advances In Experimental Medicine And Biology 2018, 1032: 37-53. PMID: 30362089, PMCID: PMC6743726, DOI: 10.1007/978-3-319-98788-0_3.ChaptersConceptsGSH biosynthesisAbundant non-protein thiolEpigenetic gene regulationNon-protein thiolsGlutathione S-transferase (GST) familyGene regulationPeroxidase familyExogenous electrophilesCellular methylationReactive oxygen speciesGSH functionsCellular concentrationRelated enzymesTranssulfuration pathwayCancer developmentOxygen speciesBiosynthesisExogenous chemicalsEnzymeTransmethylation pathwayEnhanced susceptibilityPathological conditionsIntimate involvementMillimolar rangePathway
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 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 miceSteatosis
2014
Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer
Heit C, Dong H, Chen Y, Shah YM, Thompson DC, Vasiliou V. Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer. Advances In Experimental Medicine And Biology 2014, 815: 375-387. PMID: 25427919, PMCID: PMC4323349, DOI: 10.1007/978-3-319-09614-8_22.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsReactive oxygen speciesAldehyde dehydrogenasesCritical biological functionsAlcohol dehydrogenaseFormation of proteinHuman genesBiological functionsMolecular mechanismsVariety of cancersPrimary enzymeGenetic defectsOxygen speciesEnzymeNitrogen speciesEthanol metabolismTransgenic mouse modelOxidative stressSpeciesCytochrome P450Pathogenic eventsMetabolismGenetic polymorphismsAntioxidant mechanismsAlcohol-induced toxicityAlcohol-metabolizing 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