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
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
2016
Corneal haze phenotype in Aldh3a1-null mice: In vivo confocal microscopy and tissue imaging mass spectrometry
Chen Y, Jester JV, Anderson DM, Marchitti SA, Schey KL, Thompson DC, Vasiliou V. Corneal haze phenotype in Aldh3a1-null mice: In vivo confocal microscopy and tissue imaging mass spectrometry. Chemico-Biological Interactions 2016, 276: 9-14. PMID: 28038895, DOI: 10.1016/j.cbi.2016.12.017.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAnimalsCorneaCorneal DiseasesCorneal StromaDiazepam Binding InhibitorDisease Models, AnimalDynamic Light ScatteringEpitheliumEpithelium, CornealHistonesLens, CrystallineLipidsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalPhenotypeSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationConceptsImaging mass spectrometryCorneal crystallinsNon-catalytic functionsAcyl-CoA binding proteinFirst genetic animal modelCellular transparencyCorneal epithelial homeostasisCorneal hazeEndogenous proteinsKO miceLipid localizationMixed genetic backgroundKnockout miceCorneal phenotypeEpithelial homeostasisProtein profilesWild-type corneasBinding proteinFunctional roleGenetic backgroundLens cataractMass spectrometryConfocal microscopyMolecular changesPhenotypeChronic 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 miceSteatosisHeme 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 hypothesesALDH3A1 Plays a Functional Role in Maintenance of Corneal Epithelial Homeostasis
Koppaka V, Chen Y, Mehta G, Orlicky DJ, Thompson DC, Jester JV, Vasiliou V. ALDH3A1 Plays a Functional Role in Maintenance of Corneal Epithelial Homeostasis. PLOS ONE 2016, 11: e0146433. PMID: 26751691, PMCID: PMC4708999, DOI: 10.1371/journal.pone.0146433.Peer-Reviewed Original ResearchConceptsCorneal cell proliferationCorneal epithelial homeostasisCell proliferationALDH3A1 expressionEpithelial homeostasisHuman corneal epithelial cell lineDouble knockout miceAnti-proliferation effectCorneal epithelial cell lineCorneal epithelial proliferationAldehyde dehydrogenase 1A1Epithelial cell lineCorneal differentiation markersInner ocular tissuesInverse associationFunctional roleEpithelial proliferationKnockout miceP53 expressionCorneal epitheliumOcular tissuesMouse corneaCalcium concentrationMRNA levelsEpithelial differentiation
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
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
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
2007
Hepatocyte‐specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure
Chen Y, Yang Y, Miller ML, Shen D, Shertzer HG, Stringer KF, Wang B, Schneider SN, Nebert DW, Dalton TP. Hepatocyte‐specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure. Hepatology 2007, 45: 1118-1128. PMID: 17464988, DOI: 10.1002/hep.21635.Peer-Reviewed Original ResearchConceptsLiver failureMitochondrial injuryLiver biochemistry testsSevere parenchymal damageNumerous liver diseasesMonths of ageGCLC geneHepatic failureLiver injuryParenchymal damageLiver diseaseDepletion of glutathioneHepatic steatosisHistological featuresGSH synthesisHepatic functionPostnatal dayHepatocyte deathKnockout miceRapid onsetBiochemistry testsHepatic GSHSteatosisUltrastructural examinationOxidative stress