2017
Glutathione Primes T Cell Metabolism for Inflammation
Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brüstle A, Itsumi M, Jäger C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D. Glutathione Primes T Cell Metabolism for Inflammation. Immunity 2017, 46: 675-689. PMID: 28423341, DOI: 10.1016/j.immuni.2017.03.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEncephalomyelitis, Autoimmune, ExperimentalEnergy MetabolismGlutamate-Cysteine LigaseGlutamineGlutathioneGlycolysisImmunoblottingInflammationMice, Inbred C57BLMice, KnockoutNFATC Transcription FactorsProto-Oncogene Proteins c-mycReactive Oxygen SpeciesSignal TransductionT-LymphocytesTOR Serine-Threonine KinasesConceptsReactive oxygen speciesMYC transcription factorsConditional gene targetingT cell-specific ablationGlutamate-cysteine ligaseT cell metabolismRapamycin 1Catalytic subunitMetabolic integrationTranscription factorsGene targetingMetabolic reprogrammingBiosynthetic requirementsUnexpected roleExpression of NFATAntiviral defenseCysteine ligaseCell metabolismGSH pathwayMammalian targetGSH productionMurine TGSH deficiencyOxygen speciesCell effector functions
2016
Chronic 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 ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsFatty Liver, AlcoholicGlutathioneMiceMice, KnockoutOxidation-ReductionSignal TransductionConceptsAlcoholic 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 miceSteatosisAldehyde 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
2015
ALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/β-Catenin, Notch and PI3K/Akt Signaling Pathways
Singh S, Arcaroli J, Chen Y, Thompson DC, Messersmith W, Jimeno A, Vasiliou V. ALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/β-Catenin, Notch and PI3K/Akt Signaling Pathways. PLOS ONE 2015, 10: e0121648. PMID: 25950950, PMCID: PMC4423958, DOI: 10.1371/journal.pone.0121648.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehyde Dehydrogenase, MitochondrialAnimalsCell Line, TumorColonic NeoplasmsGene Expression Regulation, NeoplasticHCT116 CellsHT29 CellsHumansMiceNeoplasm TransplantationPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, NotchRNA, Small InterferingSignal TransductionSpheroids, CellularWnt Signaling PathwayConceptsWnt/β-cateninPI3K/AktΒ-cateninSW-480 cellsColon cancer tumorigenesisWnt reporter activityPattern of expressionPI3K/Akt Signaling PathwayDual-luciferase reporterPI3K/Akt signal pathwayAkt Signaling PathwayTranscription factorsAkt signal pathwayNude mouse xenograft tumor modelColon tumorigenesisGene promoterColon adenocarcinoma cell lineMouse xenograft tumor modelALDH1B1 expressionAldehyde dehydrogenase 1B1Signaling pathwaysLuciferase reporterSize of spheroidsAdenocarcinoma cell lineXenograft tumor model
2011
Aldehyde dehydrogenases are regulators of hematopoietic stem cell numbers and B-cell development
Gasparetto M, Sekulovic S, Brocker C, Tang P, Zakaryan A, Xiang P, Kuchenbauer F, Wen M, Kasaian K, Witty MF, Rosten P, Chen Y, Imren S, Duester G, Thompson DC, Humphries RK, Vasiliou V, Smith C. Aldehyde dehydrogenases are regulators of hematopoietic stem cell numbers and B-cell development. Experimental Hematology 2011, 40: 318-329.e2. PMID: 22198153, DOI: 10.1016/j.exphem.2011.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehydesAnimalsAnimals, CongenicB-LymphocytesBone Marrow TransplantationCell CountCell CycleCell LineageCells, CulturedColony-Forming Units AssayDNA DamageEnzyme InductionGene Expression RegulationHematopoiesisHematopoietic Stem CellsLymphopeniaMiceMice, Inbred C57BLMice, KnockoutP38 Mitogen-Activated Protein KinasesRadiation ChimeraReactive Oxygen SpeciesRetinal DehydrogenaseSignal TransductionConceptsB cell developmentHematopoietic stem cellsReactive oxygen speciesMitogen-activated protein kinase activityP38 mitogen-activated protein kinase activityProtein kinase activityExcess reactive oxygen speciesOxygen speciesReactive aldehydesStem cell numbersHematopoietic stem cell numbersReactive oxygen species levelsEarly B cellsNumber of HSCsHSC biologyCell cycle distributionKinase activityOxygen species levelsAldh1a1 deficiencyGene expressionSpecies levelIntracellular signalingAldehyde dehydrogenasesDNA damageCell cycling