2016
Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny
Giebel N, Shadley J, McCarver D, Dorko K, Gramignoli R, Strom S, Yan K, Simpson P, Hines R. Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny. Drug Metabolism And Disposition 2016, 44: 1027-1037. PMID: 26921389, PMCID: PMC4931893, DOI: 10.1124/dmd.116.069344.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overBinding SitesChildChild, PreschoolChromatinChromatin Assembly and DisassemblyCytochrome P-450 CYP3AGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicGestational AgeHepatocytesHistonesHumansInfantLiverMiddle AgedNucleic Acid ConformationPromoter Regions, GeneticProtein ConformationStructure-Activity RelationshipTranscription, Genetic
2014
Tolerance to Acetaminophen Hepatotoxicity in the Mouse Model of Autoprotection Is Associated with Induction of Flavin-Containing Monooxygenase-3 (FMO3) in Hepatocytes
Rudraiah S, Rohrer P, Gurevich I, Goedken M, Rasmussen T, Hines R, Manautou J. Tolerance to Acetaminophen Hepatotoxicity in the Mouse Model of Autoprotection Is Associated with Induction of Flavin-Containing Monooxygenase-3 (FMO3) in Hepatocytes. Toxicological Sciences 2014, 141: 263-277. PMID: 24973094, PMCID: PMC4271123, DOI: 10.1093/toxsci/kfu124.Peer-Reviewed Original ResearchConceptsMale C57BL/6J miceAPAP hepatotoxicityFlavin-Containing Monooxygenase 3Protein expressionC57BL/6J miceFemale miceMouse modelMRNA levelsFirst time inductionNovel protective functionSingle doseAPAP treatmentMale miceAPAP cytotoxicityAcetaminophen pretreatmentHepatotoxic doseHigh doseAcetaminophen hepatotoxicityHepatotoxicityMice resultsCell line clonesMRNA expressionFMO3 expressionMiceAPAP
2012
Hepatobiliary Disposition of 17-OHPC and Taurocholate in Fetal Human Hepatocytes: A Comparison with Adult Human Hepatocytes
Sharma S, Ellis E, Gramignoli R, Dorko K, Tahan V, Hansel M, Mattison D, Caritis S, Hines R, Venkataramanan R, Strom S. Hepatobiliary Disposition of 17-OHPC and Taurocholate in Fetal Human Hepatocytes: A Comparison with Adult Human Hepatocytes. Drug Metabolism And Disposition 2012, 41: 296-304. PMID: 23129211, PMCID: PMC3558857, DOI: 10.1124/dmd.112.044891.Peer-Reviewed Original ResearchMeSH Keywords17 alpha-Hydroxyprogesterone CaproateAdultAge FactorsAgedBiological TransportCells, CulturedCold TemperatureCyclosporineFemaleGestational AgeHepatocytesHumansHydroxyprogesteronesKineticsMaleMembrane Transport ProteinsMiddle AgedMultidrug Resistance-Associated Protein 2RifampinRNA, MessengerTaurocholic AcidVerapamilYoung AdultConceptsHuman hepatocytesFetal human hepatocytesFetal human liverConcentration-dependent inhibitionAdult human hepatocytesBile acid transporterFetal circulationPlacental barrierRecurrent miscarriageSpontaneous abortionProgesterone metabolitesTaurocholate effluxAdult hepatocytesTherapeutic levelsLower mRNA levelsHepatobiliary dispositionHepatic transportersActivity of transportersActive efflux mechanismHuman liverHuman fetalAdverse effectsRole of transportersEfflux mechanismMRNA levels
2011
Hepatic differentiation of amniotic epithelial cells
Marongiu F, Gramignoli R, Dorko K, Miki T, Ranade A, Serra M, Doratiotto S, Sini M, Sharma S, Mitamura K, Sellaro T, Tahan V, Skvorak K, Ellis E, Badylak S, Davila J, Hines R, Laconi E, Strom S. Hepatic differentiation of amniotic epithelial cells. Hepatology 2011, 53: 1719-1729. PMID: 21374689, PMCID: PMC3103747, DOI: 10.1002/hep.24255.Peer-Reviewed Original ResearchMeSH KeywordsAmnionAnimalsCell DifferentiationCells, CulturedEpithelial CellsHepatocytesHumansMiceMice, Inbred C57BLConceptsHuman amniotic epithelial cellsRat amniotic epithelial cellsHepatocyte-like cellsAmniotic epithelial cellsEpithelial cellsEmbryonic stem cellsExtracellular matrix proteinsStem cell-derived hepatocytesProgeny of cellsSCID/beige miceCell-derived hepatocytesGerm layersAdult liver tissueLiver genesMatrix proteinsGene characteristicsHepatic differentiationStem cellsFunctional hepatocytesNoncontroversial sourceProtein expressionEndodermal originLiver diseaseMature hepatocytesBeige mice
2008
Differential regulation of human hepatic flavin containing monooxygenase 3 (FMO3) by CCAAT/enhancer-binding protein β (C/EBPβ) liver inhibitory and liver activating proteins
Klick D, Shadley J, Hines R. Differential regulation of human hepatic flavin containing monooxygenase 3 (FMO3) by CCAAT/enhancer-binding protein β (C/EBPβ) liver inhibitory and liver activating proteins. Biochemical Pharmacology 2008, 76: 268-278. PMID: 18555208, DOI: 10.1016/j.bcp.2008.05.002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBase SequenceCCAAT-Enhancer-Binding Protein-betaCell Line, TumorCells, CulturedDNAEmbryo, MammalianFemaleHepatocyte Nuclear Factor 3-betaHepatocytesHumansInfantLiverMaleMiddle AgedMolecular Sequence DataMutagenesis, Site-DirectedOxygenasesPromoter Regions, GeneticProtein Structure, TertiarySequence AlignmentSequence Analysis, DNAConceptsNuclear proteinsLiver nuclear proteinsSpecific DNA/protein interactionsPromoter activityDNA-protein binding studiesDNA/protein interactionsDNA-protein interactionsTransient expression experimentsCell nuclear proteinsDNA methylase inhibitorCCAAT enhancer-binding proteinGene regulation studiesEnhancer-binding proteinNuclear protein extractsOxidative xenobiotic metabolismHepG2 cellsFMO3 expressionTranscriptional machineryChromatin immunoprecipitationProtein interactionsPromoter functionExpression experimentsMethylase inhibitorTransient expressionDNA hypermethylation
2007
Identification and Functional Analysis of a Novel Human CYP2E1 Far Upstream Enhancer
Shadley J, Divakaran K, Munson K, Hines R, Douglas K, McCarver D. Identification and Functional Analysis of a Novel Human CYP2E1 Far Upstream Enhancer. Molecular Pharmacology 2007, 71: 1630-1639. PMID: 17353354, DOI: 10.1124/mol.106.031302.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesCells, CulturedCytochrome P-450 CYP2E1Enhancer Elements, GeneticGATA4 Transcription FactorGene Expression Regulation, EnzymologicGenetic VariationHepatocytesHumansMolecular Sequence DataPromoter Regions, GeneticRepetitive Sequences, Nucleic AcidSteroidogenic Factor 1Trans-ActivatorsTranscriptional ActivationConceptsElectrophoretic mobility shift assaysEnhancer sequencesCompetitive electrophoretic mobility shift assaysSupershift electrophoretic mobility shift assaysFunctional regulatory elementsGATA family membersMobility shift assaysGreater luciferase activityOrphan nuclear receptorSteroidogenic factor 1Luciferase reporter activityGATA sequencesFetoprotein transcription factorGATA familyChromatin immunoprecipitationTranscription factorsNuclear proteinsRegulatory elementsShift assaysRegulatory mechanismsFunctional analysisPromoter constructsDirect repeatsReporter activityUpstream region