2021
Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach
Charkoftaki G, Golla JP, Santos-Neto A, Orlicky DJ, Garcia-Milian R, Chen Y, Rattray NJW, Cai Y, Wang Y, Shearn CT, Mironova V, Wang Y, Johnson CH, Thompson DC, Vasiliou V. Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach. Toxicological Sciences 2021, 183: 338-351. PMID: 33693819, PMCID: PMC8921626, DOI: 10.1093/toxsci/kfab030.Peer-Reviewed Original ResearchConceptsDX exposureBile acid quantificationRepair responseBDF-1 miceDNA damageDose-dependent DNA damageEffects of exposureHistopathological studySubchronic exposureImmunohistochemical analysisLiver carcinogenLiver carcinogenicityLiver transcriptomicsDrinking waterMetabolomic profilingMicePotential mechanismsLiverEnvironmental chemicalsState maximum contaminant levelToxic effectsCell deathExposureOxidative stress responsePresent study
2016
Heme 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 hypothesesAldehyde Dehydrogenase 1B1 as a Modulator of Pancreatic Adenocarcinoma
Singh S, Arcaroli JJ, Orlicky DJ, Chen Y, Messersmith WA, Bagby S, Purkey A, Quackenbush KS, Thompson DC, Vasiliou V. Aldehyde Dehydrogenase 1B1 as a Modulator of Pancreatic Adenocarcinoma. Pancreas 2016, 45: 117-122. PMID: 26566217, PMCID: PMC5175203, DOI: 10.1097/mpa.0000000000000542.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehyde Dehydrogenase, MitochondrialAnimalsBiomarkers, TumorCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationFemaleGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansImmunohistochemistryMice, NudeNeoplasm InvasivenessPancreatic NeoplasmsRNA InterferenceSignal TransductionTissue Array AnalysisTransfectionTumor BurdenUp-RegulationConceptsALDH1B1 expressionPancreatic cancerPancreatic adenocarcinomaTissue microarrayHuman pancreatic cancer cell linesPancreatic cancer cell linesPancreatic cancer patientsPancreatic ductal carcinomaHuman pancreatic cancerAldehyde dehydrogenase 1B1Potential modulatory rolePancreatic cancer cellsNormal human pancreasCell linesCancer cell linesDuctal carcinomaCancer patientsModulatory roleHuman pancreasGlandular cellsTumor cellsProtein expressionCancer cellsGreater expressionAdenocarcinoma
2012
ALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets
Luo Y, Dallaglio K, Chen Y, Robinson WA, Robinson SE, McCarter MD, Wang J, Gonzalez R, Thompson DC, Norris DA, Roop DR, Vasiliou V, Fujita M. ALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets. Stem Cells 2012, 30: 2100-2113. PMID: 22887839, PMCID: PMC3448863, DOI: 10.1002/stem.1193.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehyde OxidoreductasesAnimalsApoptosisCell Transformation, NeoplasticDacarbazineDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticGene SilencingHumansIsoenzymesMelanomaMiceMice, Inbred NODMice, SCIDNeoplasm TransplantationNeoplastic Stem CellsResponse ElementsRetinal DehydrogenaseRNA, Small InterferingSkin NeoplasmsTemozolomideTretinoinConceptsCancer stem cellsPositive melanoma cellsMelanoma cellsTherapeutic targetBiomarkers of CSCsHuman melanomaPatient-derived tumor specimensMelanoma cancer stem cellsNOD/SCID miceALDH-negative cellsHigh aldehyde dehydrogenase (ALDH) activityALDH isozymesNonobese diabetic/Potential therapeutic targetDrug-induced cell deathAttractive therapeutic targetNew molecular targetsHuman melanoma cellsStem cellsMelanoma stem cellsAldehyde dehydrogenase activityHuman melanoma stem cellsNSG miceCell cycle arrestImmunodeficiency miceEffect of chronic glutathione deficiency on the behavioral phenotype of Gclm(−/−) knockout mice
Chen Y, Curran CP, Nebert DW, Patel KV, Williams MT, Vorhees CV. Effect of chronic glutathione deficiency on the behavioral phenotype of Gclm(−/−) knockout mice. Neurotoxicology And Teratology 2012, 34: 450-457. PMID: 22580179, PMCID: PMC3404268, DOI: 10.1016/j.ntt.2012.04.009.Peer-Reviewed Original ResearchConceptsGlutamate-cysteine ligase modifier subunitMorris water mazeKO miceKnockout miceWater mazeOxidative stressChronic glutathione deficiencyPostnatal day 60Novel object recognitionWild-type littermatesTime of conceptionChronic GSH depletionChronic oxidative stressOpen-field activityKnockout mouse lineNormal spatial learningControl brain regionsAcoustic startleBehavioral abnormalitiesPostnatal lifeBrain regionsNeurodegenerative disordersDay 60Phenotyping testsMiceEffect of vitamin C deficiency during postnatal development on adult behavior: functional phenotype of Gulo(−/−) knockout mice
Chen Y, Curran C, Nebert D, Patel K, Williams M, Vorhees C. Effect of vitamin C deficiency during postnatal development on adult behavior: functional phenotype of Gulo(−/−) knockout mice. Genes Brain & Behavior 2012, 11: 269-277. PMID: 22296218, PMCID: PMC3325330, DOI: 10.1111/j.1601-183x.2011.00762.x.Peer-Reviewed Original ResearchConceptsGulo-/- miceBiosynthesis of ascorbateImportant cellular antioxidantAscorbate deficiencyL-gulono-γ-lactone oxidaseAmount of ascorbateGULO geneRate-limiting enzymeReactive oxygen speciesAerobic respirationAbnormal behavioral phenotypesMetabolic processesVitamin CCellular antioxidantsSupplemental vitamin CFunctional phenotypeOxygen speciesVitamin C deficiencyWild-type littermatesMild motor deficitsSpeciesBehavioral phenotypesPhenotypeDopamine agonistsMotor deficits
2011
Glutathione-Deficient Mice Are Susceptible to TCDD-Induced Hepatocellular Toxicity but Resistant to Steatosis
Chen Y, Krishan M, Nebert DW, Shertzer HG. Glutathione-Deficient Mice Are Susceptible to TCDD-Induced Hepatocellular Toxicity but Resistant to Steatosis. Chemical Research In Toxicology 2011, 25: 94-100. PMID: 22082335, DOI: 10.1021/tx200242a.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAspartate AminotransferasesEnvironmental PollutantsFatty LiverFemaleGamma-GlutamyltransferaseGene Expression RegulationGlutamate-Cysteine LigaseGlutathioneLipid MetabolismLiverMiceMice, Inbred C57BLMice, KnockoutNon-alcoholic Fatty Liver DiseaseOligonucleotide Array Sequence AnalysisPolychlorinated DibenzodioxinsReverse Transcriptase Polymerase Chain ReactionConceptsTetrachlorodibenzo-p-dioxinGlutamic oxaloacetic transaminaseGlutamate-cysteine ligaseHepatocellular toxicityPlasma glutamic oxaloacetic transaminaseWild-type female miceImpaired lipid metabolismTissue GSH levelsTCDD-induced hepatotoxicityGlutathione-deficient miceΓ-glutamyl transferaseHepatocellular injuryWT miceHepatocellular damageLipid metabolism genesFemale miceWT littermatesTransgenic miceCDNA microarray expression analysisDe novo GSH biosynthesisOxaloacetic transaminaseLipid metabolismConsecutive daysSteatosisMiceLipid 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
2009
Early onset senescence occurs when fibroblasts lack the glutamate–cysteine ligase modifier subunit
Chen Y, Johansson E, Fan Y, Shertzer HG, Vasiliou V, Nebert DW, Dalton TP. Early onset senescence occurs when fibroblasts lack the glutamate–cysteine ligase modifier subunit. Free Radical Biology And Medicine 2009, 47: 410-418. PMID: 19427898, PMCID: PMC2773044, DOI: 10.1016/j.freeradbiomed.2009.05.003.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsBeta-GalactosidaseCell Culture TechniquesCell CycleCell Growth ProcessesCellular SenescenceCyclin-Dependent Kinase Inhibitor p21DNA DamageFemaleFetusFibroblastsFree Radical ScavengersGlutamate-Cysteine LigaseGlutathioneMiceMice, Inbred C57BLMice, KnockoutPregnancyProtein SubunitsReactive Oxygen SpeciesTumor Suppressor Protein p53ConceptsGlutamate-cysteine ligasePremature senescenceCellular redox environmentCellular antioxidant glutathionePrimary murine fibroblastsSenescence-associated beta-galactosidase activityCell cycle arrestInduction of p53Beta-galactosidase activityPrevents premature senescenceCatalytic subunitCellular senescenceGrowth arrestGlutamate cysteine ligase modifierModifier subunitP21 proteinPhysiological roleSenescenceDNA damageRedox environmentCycle arrestMurine fibroblastsGSH synthesisN-acetylcysteine increasesPrimary cells
2008
Knock-In Mouse Lines Expressing either Mitochondrial or Microsomal CYP1A1: Differing Responses to Dietary Benzo[a]pyrene as Proof of Principle
Dong H, Dalton TP, Miller ML, Chen Y, Uno S, Shi Z, Shertzer HG, Bansal S, Avadhani NG, Nebert DW. Knock-In Mouse Lines Expressing either Mitochondrial or Microsomal CYP1A1: Differing Responses to Dietary Benzo[a]pyrene as Proof of Principle. Molecular Pharmacology 2008, 75: 555-567. PMID: 19047483, PMCID: PMC2684908, DOI: 10.1124/mol.108.051888.Peer-Reviewed Original ResearchConceptsMitochondrial importCryptic targeting signalMitochondrial-targeting signalSignal recognition particleInner mitochondrial membraneDifferent substrate specificitiesMouse linesCYP1A1 proteinTargeting signalsRecognition particleCYP1A1 enzymeSubstrate specificityMitochondrial membraneEndoplasmic reticulumBaP toxicityPhysiological functionsTerminal processingProteinCytosolic peptidasesProof of principleMutationsEnzymeInducer propertiesCYP1B1 mRNAMicrosomal CYP1A1