2023
Fatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis
Chen Y, Holland K, Shertzer H, Nebert D, Dalton T. Fatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis. Antioxidants 2023, 12: 448. PMID: 36830006, PMCID: PMC9952205, DOI: 10.3390/antiox12020448.Peer-Reviewed Original ResearchDKO miceEpileptic seizuresKnockout miceAA supplementationAdult DKO miceFatal epileptic seizuresSpontaneous epileptic seizuresDietary ascorbic acidTissue GSH levelsDouble knockout miceNormal brain functionFunctional crosstalkNeuronal lossHippocampal pathologyGlutamatergic neurotransmissionGlial proliferationBrain damageNeuronal healthPostnatal dayBrain pathologyRate-limiting enzymeSeizuresBrain functionMiceGSH levels
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
2020
Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer
Golla JP, Kandyliari A, Tan WY, Chen Y, Orlicky DJ, Thompson DC, Shah YM, Vasiliou V. Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer. Chemico-Biological Interactions 2020, 331: 109274. PMID: 33007288, PMCID: PMC9201852, DOI: 10.1016/j.cbi.2020.109274.Peer-Reviewed Original ResearchConceptsColorectal cancerColonic adenomasPresent preliminary studyMouse modelConsecutive daysLarge colonic adenomaPresence of adenomasApc mouse modelColon tumor growthMouse xenograft modelColon epithelial cellsFurther mechanistic studiesCancer mortalityKO miceLeading causeColorectal adenomasCRC developmentImmunohistochemical analysisXenograft modelTumor growthColorectal tumorigenesisAdenomasExpression scoreMale ApcMiceGlutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function
Kurniawan H, Franchina DG, Guerra L, Bonetti L, -Baguet LS, Grusdat M, Schlicker L, Hunewald O, Dostert C, Merz MP, Binsfeld C, Duncan GS, Farinelle S, Nonnenmacher Y, Haight J, Das Gupta D, Ewen A, Taskesen R, Halder R, Chen Y, Jäger C, Ollert M, Wilmes P, Vasiliou V, Harris IS, Knobbe-Thomsen CB, Turner JD, Mak TW, Lohoff M, Meiser J, Hiller K, Brenner D. Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function. Cell Metabolism 2020, 31: 920-936.e7. PMID: 32213345, PMCID: PMC7265172, DOI: 10.1016/j.cmet.2020.03.004.Peer-Reviewed Original ResearchConceptsSuppressive capacityRegulatory T cell functionTreg suppressive capacityTreg-specific ablationAnti-tumor responseT cell functionSerine metabolismTreg functionalityFoxp3 expressionPrevent autoimmunitySevere autoimmunityTreg differentiationImmune homeostasisEffector TGlutamate-cysteine ligaseCell responsesTregsMTOR activationMutant miceCell functionAutoimmunitySerine availabilityGlutathione synthesisCysteine ligaseMice
2017
Transcriptomic analysis and plasma metabolomics in Aldh16a1-null mice reveals a potential role of ALDH16A1 in renal function
Charkoftaki G, Chen Y, Han M, Sandoval M, Yu X, Zhao H, Orlicky DJ, Thompson DC, Vasiliou V. Transcriptomic analysis and plasma metabolomics in Aldh16a1-null mice reveals a potential role of ALDH16A1 in renal function. Chemico-Biological Interactions 2017, 276: 15-22. PMID: 28254523, PMCID: PMC5725231, DOI: 10.1016/j.cbi.2017.02.013.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAnimalsDown-RegulationGene Expression ProfilingKidneyLipidsMetabolomicsMiceMice, Inbred C57BLMice, KnockoutMonocarboxylic Acid TransportersMultidrug Resistance-Associated ProteinsMutation, MissenseSequence Analysis, RNASodium-Phosphate Cotransporter Proteins, Type IUp-RegulationConceptsUric acid homeostasisPlasma metabolomicsElevated serum uric acid levelsSerum uric acid levelsDistal convoluted tubule cellsAcid homeostasisUric acid levelsZone 3 hepatocytesConvoluted tubule cellsSingle nucleotide variantsRenal functionKO miceLipid profileKnockout miceMissense single nucleotide variantsTubule cellsRNA-seq analysisKidneyMouse linesAcid levelsMicePotential roleLipid metabolic processMetabolomic analysisCellular lipids
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
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
2012
Effect 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: 500-500. DOI: 10.1111/j.1601-183x.2012.00792.x.Peer-Reviewed Original ResearchEffect 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 testsMice
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 daysSteatosisMice
2010
Glutathione deficient C57BL/6J mice are not sensitized to ozone-induced lung injury
Johansson E, Wesselkamper SC, Shertzer HG, Leikauf GD, Dalton TP, Chen Y. Glutathione deficient C57BL/6J mice are not sensitized to ozone-induced lung injury. Biochemical And Biophysical Research Communications 2010, 396: 407-412. PMID: 20417186, PMCID: PMC2892220, DOI: 10.1016/j.bbrc.2010.04.105.Peer-Reviewed Original ResearchConceptsOzone-induced lung injuryGlutamate-cysteine ligase modifier subunitLung injuryLung hyperpermeabilityDegree of neutrophiliaBronchoalveolar lavage fluidWild-type miceInflammatory gene expressionPulmonary susceptibilityLavage fluidCompensatory augmentationKnockout miceTotal protein concentrationPpm ozoneMiceModifier subunitMRNA levelsAntioxidant defenseMember 2Antioxidant glutathioneMetallothionein-1GSH depletionHyperpermeabilityInjuryAntioxidant response
2008
Generation of a ‘humanized’ hCYP1A1_1A2_Cyp1a1/1a2(−/−)_Ahrd mouse line harboring the poor-affinity aryl hydrocarbon receptor
Shi Z, Chen Y, Dong H, Amos-Kroohs RM, Nebert DW. Generation of a ‘humanized’ hCYP1A1_1A2_Cyp1a1/1a2(−/−)_Ahrd mouse line harboring the poor-affinity aryl hydrocarbon receptor. Biochemical And Biophysical Research Communications 2008, 376: 775-780. PMID: 18814841, PMCID: PMC2582963, DOI: 10.1016/j.bbrc.2008.09.068.Peer-Reviewed Original ResearchConceptsHigh-affinity aryl hydrocarbon receptorAryl hydrocarbon receptorDose-response curveMouse linesHydrocarbon receptorCYP1A2 geneHuman risk assessmentC57BL/6J miceNew mouse lineDBA/2J miceCYP1A2 substratesMiceCYP1A2 mRNACYP1A1Mouse CYP1A1Human CYP1A1ReceptorsFunctional CYP1A1Vast majorityRisk assessmentLungKidney