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
2010
Oral N-acetylcysteine rescues lethality of hepatocyte-specific Gclc-knockout mice, providing a model for hepatic cirrhosis
Chen Y, Johansson E, Yang Y, Miller ML, Shen D, Orlicky DJ, Shertzer HG, Vasiliou V, Nebert DW, Dalton TP. Oral N-acetylcysteine rescues lethality of hepatocyte-specific Gclc-knockout mice, providing a model for hepatic cirrhosis. Journal Of Hepatology 2010, 53: 1085-1094. PMID: 20810184, PMCID: PMC2970663, DOI: 10.1016/j.jhep.2010.05.028.Peer-Reviewed Original ResearchAcetylcysteineAdministration, OralAnimalsAntioxidantsBase SequenceCytokinesDisease Models, AnimalDNA PrimersGene Expression ProfilingGlutamate-Cysteine LigaseGlutathioneHepatocytesLiverLiver CirrhosisMiceMice, KnockoutMicroscopy, Electron, TransmissionMitochondria, LiverOxidative StressRNA, Messenger
2007
Oxidative and electrophilic stress induces multidrug resistance–associated protein transporters via the nuclear factor‐E2–related factor‐2 transcriptional pathway
Maher JM, Dieter MZ, Aleksunes LM, Slitt AL, Guo G, Tanaka Y, Scheffer GL, Chan JY, Manautou JE, Chen Y, Dalton TP, Yamamoto M, Klaassen CD. Oxidative and electrophilic stress induces multidrug resistance–associated protein transporters via the nuclear factor‐E2–related factor‐2 transcriptional pathway. Hepatology 2007, 46: 1597-1610. PMID: 17668877, DOI: 10.1002/hep.21831.Peer-Reviewed Original ResearchMeSH Keywords5' Flanking RegionAnimalsAntioxidantsButylated HydroxyanisoleCell Line, TumorFluorescent Antibody Technique, IndirectGene Expression RegulationGlutamate-Cysteine LigaseGlutathioneHepatocytesLiverMiceMice, Inbred C57BLMice, KnockoutMultidrug Resistance-Associated ProteinsNF-E2-Related Factor 2Oxidative StressPromoter Regions, GeneticPyrazinesReverse Transcriptase InhibitorsThionesThiophenesConceptsTranscriptional pathwaysBinding of Nrf2Nrf2 transcriptional pathwayNrf2 target genesMarked geneAdenosine triphosphate-dependent transportersChromatin immunoprecipitationElectrophilic stressNuclear Nrf2 levelsTarget genesRegulatory pathwaysCoordinated inductionPromoter regionProtein transportersMultidrug resistance-associated proteinNrf2-null miceResponse elementResistance-associated proteinHepa1c1c7 cellsProtein inductionFactor 2 (Nrf2) activatorQuinone oxidoreductase 1MRP transportersTransportersNrf2 levelsHepatocyte‐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