2022
Lipidomics and Redox Lipidomics Indicate Early Stage Alcohol‐Induced Liver Damage
Koelmel JP, Tan WY, Li Y, Bowden JA, Ahmadireskety A, Patt AC, Orlicky DJ, Mathé E, Kroeger NM, Thompson DC, Cochran JA, Golla JP, Kandyliari A, Chen Y, Charkoftaki G, Guingab‐Cagmat J, Tsugawa H, Arora A, Veselkov K, Kato S, Otoki Y, Nakagawa K, Yost RA, Garrett TJ, Vasiliou V. Lipidomics and Redox Lipidomics Indicate Early Stage Alcohol‐Induced Liver Damage. Hepatology Communications 2022, 6: 513-525. PMID: 34811964, PMCID: PMC8870008, DOI: 10.1002/hep4.1825.Peer-Reviewed Original ResearchConceptsAlcoholic fatty liver diseaseEthanol-treated miceFatty liver diseaseAlcohol consumption altersRegulation of triglycerideLiver lipidomeRegulation of phosphatidylcholineHepatic inflammationLiver biopsyLiver diseaseComprehensive time-course studyLiver damageHistological signsEarly biomarkersHistological markersMouse modelTime-course studyLiver tissueTriglyceridesHistological analysisEarly detectionLipid accumulationLiverMajor lipid classesDiet model
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 pathwayHepatic metabolic adaptation in a murine model of glutathione deficiency
Chen Y, Golla S, Garcia-Milian R, Thompson DC, Gonzalez FJ, Vasiliou V. Hepatic metabolic adaptation in a murine model of glutathione deficiency. Chemico-Biological Interactions 2019, 303: 1-6. PMID: 30794799, PMCID: PMC6743730, DOI: 10.1016/j.cbi.2019.02.015.Peer-Reviewed Original ResearchConceptsCellular non-protein thiolsMetabolic adaptationGlutamate-cysteine ligase modifier subunitNon-protein thiolsHepatic metabolic adaptationCellular redoxGlobal profilingGSH homeostasisModifier subunitLiver developmentBiochemical mechanismsMetabolic homeostasisAmino acidsGclm null miceDefense mechanismsEnvironmental insultsOxidative damageFatty liver developmentNull miceSpectrum of changesNucleic acidsMetabolic signaturesPivotal roleHomeostasisGlutathione deficiency
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
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
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