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 pathway
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 rangePathwayEngineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer
Marshall S, Chen Y, Singh S, Berrios-Carcamo P, Heit C, Apostolopoulos N, Golla JP, Thompson DC, Vasiliou V. Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer. Advances In Experimental Medicine And Biology 2018, 1032: 203-221. PMID: 30362100, PMCID: PMC6743736, DOI: 10.1007/978-3-319-98788-0_14.ChaptersConceptsExact molecular mechanismsMouse modelCellular proteinsEthanol-induced tissue injuryEthanol metabolismEngineered Animal ModelsMolecular mechanismsAldehyde dehydrogenasesLong-term alcohol abuseAlcohol-induced diseasesFurther tissue damageAntioxidant glutathioneImportant mouse modelsCurrent understandingLeading causeTissue injuryIntracellular generationAlcohol abuseAlcohol consumptionAnimal modelsPathogenic eventsPathophysiological consequencesTissue damageMetabolismDNA adducts
2016
Quantification 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
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
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
The Role of CYP2E1 in Alcohol Metabolism and Sensitivity in the Central Nervous System
Heit C, Dong H, Chen Y, Thompson DC, Deitrich RA, Vasiliou VK. The Role of CYP2E1 in Alcohol Metabolism and Sensitivity in the Central Nervous System. Subcellular Biochemistry 2013, 67: 235-247. PMID: 23400924, PMCID: PMC4314297, DOI: 10.1007/978-94-007-5881-0_8.ChaptersConceptsCentral nervous systemNervous systemBlood-brain barrierRole of CYP2E1Certain brain cellsCytochrome P450 2E1Particular brain regionsMotor incoordinationBrain barrierSleep inductionEthanol consumptionBrain cellsAlcohol consumptionBrain regionsP450 2E1Alcohol metabolismEthanol metabolismBehavioral effectsCYP2E1Major enzymeLocal productionMetabolismIncoordinationBrain
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-Ionization