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
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
2005
Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants
Koukouritaki S, Poch M, Cabacungan E, McCarver D, Hines R. Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants. Molecular Pharmacology 2005, 68: 383-392. PMID: 15858076, DOI: 10.1124/mol.105.012062.Peer-Reviewed Original ResearchConceptsFlavin-containing monooxygenasesFunctional analysisSingle nucleotide polymorphism (SNP) discoveryMembrane interaction domainHaplotype variantsSite-directed mutagenesisConsensus splice sitesFMO3 expressionUpstream SNPsGene functionPolymorphism discoveryNear complete lossRossmann foldFAD bindingInteraction domainSingle nucleotide polymorphismsRegion haplotypesHaplotype 8Exon SNPsFMO enzymesPromoter activityIntron SNPSequence analysisSNP frequenciesLuciferase construct
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 timing