2022
Liver metabolomics identifies bile acid profile changes at early stages of alcoholic liver disease in mice
Charkoftaki G, Tan WY, Berrios-Carcamo P, Orlicky DJ, Golla JP, Garcia-Milian R, Aalizadeh R, Thomaidis NS, Thompson DC, Vasiliou V. Liver metabolomics identifies bile acid profile changes at early stages of alcoholic liver disease in mice. Chemico-Biological Interactions 2022, 360: 109931. PMID: 35429548, PMCID: PMC9364420, DOI: 10.1016/j.cbi.2022.109931.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseaseEthanol-consuming miceAlcohol consumptionLiver diseaseDevelopment of ALDBile acid changesChronic alcohol drinkingChronic alcohol consumptionLieber-DeCarli dietAlcohol-induced alterationsGlobal healthcare problemBile acid biosynthesisAlcohol drinkingLiver histopathologyTissue injuryClinical consequencesUntargeted metabolomics analysisEarly stagesComplex pathologyMinimal changesUntargeted metabolomics approachEarly onsetHealthcare problemMiceLiver
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
2016
Catalase deletion promotes prediabetic phenotype in mice
Heit C, Marshall S, Singh S, Yu X, Charkoftaki G, Zhao H, Orlicky DJ, Fritz KS, Thompson DC, Vasiliou V. Catalase deletion promotes prediabetic phenotype in mice. Free Radical Biology And Medicine 2016, 103: 48-56. PMID: 27939935, PMCID: PMC5513671, DOI: 10.1016/j.freeradbiomed.2016.12.011.Peer-Reviewed Original ResearchConceptsCatalase-knockout (KO) micePancreatic morphological changesImpaired glucose toleranceDevelopment of diabetesSerum insulin levelsPre-diabetic phenotypePre-diabetic statusRNA-seq analysisSignal transduction moleculesMuscle lipid depositionSignal transduction mechanismsGlucose toleranceMetabolic syndromeInsulin levelsNormal chowHepatic triglyceridesObese phenotypeLiver morphologyHigh riskPrediabetic phenotypesKnockout miceLipid depositionBody weightTransduction moleculesMetabolic regulationQuantification of Neural Ethanol and Acetaldehyde Using Headspace GC‐MS
Heit C, Eriksson P, Thompson DC, Charkoftaki G, Fritz KS, Vasiliou V. Quantification of Neural Ethanol and Acetaldehyde Using Headspace GC‐MS. Alcohol Clinical And Experimental Research 2016, 40: 1825-1831. PMID: 27501276, PMCID: PMC5008984, DOI: 10.1111/acer.13156.Peer-Reviewed Original ResearchConceptsAlcohol drinking behaviorEtOH metabolitesMurine brain tissueACh levelsAlcohol consumptionACh concentrationBrain tissueLiver tissueAChAlcohol addictionACh formationBrainDrinking behaviorLow micromolar rangeAlcohol researchTissue analysisTissueNanomolar rangeChromatography-mass spectrometry methodQuantitative assayMass spectrometry methodActive agentsMicromolar rangeSensitive gas chromatography-mass spectrometry methodHeme 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 hypotheses
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