2016
Age-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny
Hines R, Simpson P, McCarver D. Age-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny. Drug Metabolism And Disposition 2016, 44: 959-966. PMID: 26825642, DOI: 10.1124/dmd.115.068957.Peer-Reviewed Original ResearchConceptsHepatic carboxylesterase 1Weeks of ageCarboxylesterase 1CES2 expressionAge groupsYounger age groupsCES1 expressionLiver diseaseAdverse outcomesMetabolic clearancePmol/Older groupOlder individualsWestern blottingLiver samplesWeeksEnvironmental chemicalsPostnatal ontogenyMicrosomal proteinMedian valueAgeCytosolic fractionGroupExpressionSubjects
2012
Age‐Dependent Expression of Human Drug‐Metabolizing Enzymes
Hines R. Age‐Dependent Expression of Human Drug‐Metabolizing Enzymes. 2012, 1-33. DOI: 10.1002/9780470921920.edm085.Peer-Reviewed Original Research
2008
CYP3A4 regulation by DBP and E4BP4 transcription factors
Maas K, Le M, Hines R. CYP3A4 regulation by DBP and E4BP4 transcription factors. The FASEB Journal 2008, 22: 921.7-921.7. DOI: 10.1096/fasebj.22.1_supplement.921.7.Peer-Reviewed Original ResearchD-element binding proteinDose-dependent mannerCYP3A4 promoter activityPromoter activityLuciferase expressionCYP3A4 regulationPostnatal liverLuciferase reporterProtein 4Luciferase activityHepG2 cellsE4BP4Binding proteinDevelopmental expression patternsResponsive elementExpression patternsHigh affinityProximal promoterTranscription factorsExpressionActivityRegulatory Polymorphisms and their Contribution to Interindividual Differences in the Expression of Enzymes Influencing Drug and Toxicant Disposition
Hines R, Koukouritaki S, Poch M, Stephens M. Regulatory Polymorphisms and their Contribution to Interindividual Differences in the Expression of Enzymes Influencing Drug and Toxicant Disposition. Drug Metabolism Reviews 2008, 40: 263-301. PMID: 18464046, DOI: 10.1080/03602530801952682.Peer-Reviewed Original ResearchConceptsRegulatory polymorphismsRegulatory sequencesHuman proteinsSelection pressureGene expressionCo-dominant traitEvolutionary perspectiveXenobiotic metabolismEnvironmental changesToxicant dispositionUnexpected paucityCurrent understandingHeterozygous stateTraitsPolymorphismSuch variationExpressionKnowledge gapsGenesProteinFitnessSequenceMetabolismVariationDrug disposition
2007
Regulation of CYP3A4 Expression by PAR Transcription Factors
Mantei K, Le M, Klick D, Vyhlidal C, Hines R. Regulation of CYP3A4 Expression by PAR Transcription Factors. The FASEB Journal 2007, 21: a1183-a1183. DOI: 10.1096/fasebj.21.6.a1183-a.Peer-Reviewed Original ResearchD-element binding proteinCYP3A4 expressionHepatic leukemia factorCYP3A4 promoter activityAdult human liverAbundant cytochrome P450CYP3A4 promoterHuman liverPostnatal liverProtein 4DBP expressionPAR familyEmbryonic factorsHepG2 cellsTranscription factorsCytochrome P450LiverFunctional significanceCo-transfection experimentsBinding proteinPromoter activityExpressionReporter constructsFactorsFactor familyMechanisms Regulating Human FMO3 Transcription
Klick D, Hines R. Mechanisms Regulating Human FMO3 Transcription. Drug Metabolism Reviews 2007, 39: 419-442. PMID: 17786630, DOI: 10.1080/03602530701498612.Peer-Reviewed Original ResearchConceptsGC-box binding proteinsHepG2 cellsPromoter characterizationLiver nuclear proteinsNuclear proteinsTransient expressionFMO enzymesDevelopmental expressionBinding proteinTranscriptionAdult regulationProteinSpecific mechanismsEnzymeExpressionCellsNFYMajor roleYY1USF1Oxidative drugsHeterodimersMonooxygenasesReporterIsoforms
2006
Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3
Hines R. Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3. Expert Opinion On Drug Metabolism & Toxicology 2006, 2: 41-49. PMID: 16863467, DOI: 10.1517/17425255.2.1.41.Peer-Reviewed Original ResearchConceptsAnimal modelsMost animal modelsHuman fetal liverAdult human liverAdverse reactionsToxicant dispositionTherapeutic efficacyDrug metabolismHuman liverFetal liverToxicant metabolismDrugsEnzyme expressionCytochrome P450-dependent monooxygenasesLiverP450-dependent monooxygenasesFamily membersFMO enzymesRecent studiesMonooxygenases 1FMO3MetabolismExpression patternsExpression
2003
Workshop Overview: Use of Genomic Data in Risk Assessment
Cunningham M, Bogdanffy M, Zacharewski T, Hines R. Workshop Overview: Use of Genomic Data in Risk Assessment. Toxicological Sciences 2003, 73: 209-215. PMID: 12700425, DOI: 10.1093/toxsci/kfg071.Peer-Reviewed Original ResearchConceptsGenomic technologiesGenomic researchHigh-throughput genomic technologiesHigh-throughput proteomicsHuman Genome ProjectPosttranslational eventsGenetic compositionThroughput proteomicsNew high-throughput genomic technologiesGenetic variabilityGenome ProjectGenomic dataDNA microarraysDifferent genesExpression levelsSpecific cellsGenesToxicological responsesToxicant exposureRecent advancesProteomicsMicroarrayBetter understandingIndividual adaptiveExpression
2002
Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression
Koukouritaki S, Simpson P, Yeung C, Rettie A, Hines R. Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression. Pediatric Research 2002, 51: 236-243. PMID: 11809920, DOI: 10.1203/00006450-200202000-00018.Peer-Reviewed Original ResearchConceptsFlavin-containing monooxygenasesExpression patternsSpecies-specific expression patternsFMO3 expressionTemporal expression patternsMajor adult isoformFMO genesPotential control mechanismsDevelopmental expressionProtein levelsAdult isoformsWestern blottingExpressionEmbryosNumerous therapeuticsIsoformsMonooxygenases 1Most individualsFMO3Microsomal fractionHuman liver samplesIntermediate levelsControl mechanismsGenesPrecise timingGENETIC POLYMORPHISMS OF FLAVIN-CONTAINING MONOOXYGENASE (FMO)
Krueger S, Williams D, Yueh M, Martin S, Hines R, Raucy J, Dolphin C, Shephard E, Phillips I. GENETIC POLYMORPHISMS OF FLAVIN-CONTAINING MONOOXYGENASE (FMO). Drug Metabolism Reviews 2002, 34: 523-532. PMID: 12214664, DOI: 10.1081/dmr-120005653.Peer-Reviewed Original ResearchConceptsFlavin-Containing MonooxygenaseAdult human liverPercent of individualsPlethora of drugsTrimethylamine N-oxygenationDrug metabolismHuman liverGenetic polymorphismsHispanic descentPremature stop codonPolymorphic expressionLungPreliminary evidenceFunctional FMO2African descentXenobiotic toxicityMammalian flavinN-oxygenationFMO2TrimethylaminuriaEthylene thioureaPolymorphismAllelesPatientsExpression
2001
Molecular regulation of genes encoding xenobiotic-metabolizing enzymes: mechanisms involving endogenous factors.
Hines R, Luo Z, Cresteil T, Ding X, Prough R, Fitzpatrick J, Ripp S, Falkner K, Ge N, Levine A, Elferink C. Molecular regulation of genes encoding xenobiotic-metabolizing enzymes: mechanisms involving endogenous factors. Drug Metabolism And Disposition 2001, 29: 623-33. PMID: 11302926.Peer-Reviewed Original ResearchConceptsDevelopmental-specific expressionSignal transduction pathwaysMolecular regulationTransduction pathwaysCommon signal transduction pathwayReceptor-mediated signal transduction pathwaysRegulation of xenobioticGenome levelTranscription factorsMolecular mechanismsMolecular biologyEndogenous factorsGenesRegulatory systemXenobiotic-metabolizing enzymesEnzymeRegulationExpressionCytochrome P450Fundamental rolePathwayRapid proliferationTissueBiologyExperimental therapeutics
2000
Developmental regulation of the L-type calcium channel α1C subunit expression in heart
Leu L, O'Hara D, Cala S, Poornima I, Hines R, Marsh J. Developmental regulation of the L-type calcium channel α1C subunit expression in heart. Molecular And Cellular Biochemistry 2000, 205: 101-109. PMID: 10821427, DOI: 10.1023/a:1007013900827.Peer-Reviewed Original ResearchConceptsRNase protection assaysProtection assaysNorthern analysisΑ1C subunitSize of proteinsAlternative splicingAbundance of mRNADevelopmental regulationSmaller transcriptTranscript sizeNative proteinKD proteinMolecular massDevelopmental stagesProteinSubunitsAdult ventriclesTranscriptsPostnatal developmentAbundanceExpressionSubunit expressionCalcium channel propertiesChannel propertiesReceptor message
1986
The molecular biology of the polycyclic aromatic hydrocarbon inducible cytochrome P‐450; the past is prologue
Iversen P, Hines R, Bresnick E. The molecular biology of the polycyclic aromatic hydrocarbon inducible cytochrome P‐450; the past is prologue. BioEssays 1986, 4: 15-19. PMID: 3790107, DOI: 10.1002/bies.950040105.Peer-Reviewed Original ResearchConceptsRegulation of expressionEnzyme systemUbiquitous familySubstrate specificityGene expressionMultiple isozymesMolecular biologyCytochrome PToxic lesionsExogenous compoundsOxidative metabolismMechanisms of metabolismExpressionInducible cytochrome PIsozymesComplete understandingMetabolismBiochemical pharmacologyOrganismsBiologySpeciesRegulationWide varietyCascadeCurrent notions