2018
Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis
Pan Q, Zhang X, Zhang L, Cheng Y, Zhao N, Li F, Zhou X, Chen S, Li J, Xu S, Huang D, Chen Y, Li L, Wang H, Chen W, Cai SY, Boyer JL, Chai J. Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis. Gastroenterology 2018, 155: 1578-1592.e16. PMID: 30063921, PMCID: PMC6221191, DOI: 10.1053/j.gastro.2018.07.031.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver tissueBile acidsHepatic levelsHepatoma cell lineFibroblast growth factor 19Cholestatic liver tissuesEfflux transportersCholic acid dietDevelopment of cholestasisGrowth factor 19Sprague-Dawley ratsShorter survival timeBile acid homeostasisHealthy liver tissueReal-time quantitative polymerase chain reactionNuclear factor κBCell linesQuantitative polymerase chain reactionHuman primary hepatocytesMessenger RNALiver injuryCa dietControl miceC57BL/6J miceCenicriviroc, a cytokine receptor antagonist, potentiates all‐trans retinoic acid in reducing liver injury in cholestatic rodents
Yu D, Cai S, Mennone A, Vig P, Boyer JL. Cenicriviroc, a cytokine receptor antagonist, potentiates all‐trans retinoic acid in reducing liver injury in cholestatic rodents. Liver International 2018, 38: 1128-1138. PMID: 29356312, PMCID: PMC6032984, DOI: 10.1111/liv.13698.Peer-Reviewed Original ResearchConceptsBile acid pool sizeTrans retinoic acidAcid pool sizePlasma liver enzymesLiver injurySuperior therapeutic effectLiver necrosisLiver enzymesT cellsTherapeutic effectRetinoic acidAntagonist of CCR2Hepatic inflammatory cellsCholestatic liver injuryBile duct proliferationBody weight ratioCholestatic liver diseasePro-inflammatory cytokinesCytokine receptor antagonistsHepatic hydroxyproline contentExpression of cytokinesDuct-ligated ratsBile acid synthesisHepatic infiltrationLiver disease
2016
CFTR-associated ligand is a negative regulator of Mrp2 expression
Li M, Soroka CJ, Harry K, Boyer JL. CFTR-associated ligand is a negative regulator of Mrp2 expression. American Journal Of Physiology - Cell Physiology 2016, 312: c40-c46. PMID: 27834195, PMCID: PMC5283898, DOI: 10.1152/ajpcell.00100.2016.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCells, CulturedChlorocebus aethiopsCOS CellsDown-RegulationGene Expression RegulationGolgi Matrix ProteinsHepatocytesHumansMaleMembrane ProteinsMembrane Transport ProteinsMiceMultidrug Resistance-Associated Protein 2Multidrug Resistance-Associated ProteinsRatsRats, Sprague-DawleySignal TransductionConceptsPull-down assaysGST pull-down assaysCOOH-terminal PDZNegative regulatorCotransfected COS-7 cellsGlutathione S-transferase fusion proteinS-transferase fusion proteinATP-binding cassette (ABC) transportersTrans-Golgi networkCystic fibrosis transmembrane conductance regulatorProtein-protein interactionsExchanger regulatory factor 1Fibrosis transmembrane conductance regulatorStreptavidin pull-down assaysTransmembrane conductance regulatorCOS-7 cellsRegulatory factor 1PDZ domainCell surface expressionPosttranscriptional regulationTransmembrane proteinPlasma membraneLLC-PK1 cellsCassette transportersCOS-7
2010
Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells
He H, Mennone A, Boyer JL, Cai S. Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells. Hepatology 2010, 53: 548-557. PMID: 21274875, PMCID: PMC3069505, DOI: 10.1002/hep.24047.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsBile DuctsCell ProliferationCells, CulturedCholestasis, IntrahepaticCholesterol 7-alpha-HydroxylaseCollagen Type ICollagen Type I, alpha 1 ChainDisease Models, AnimalHepatocytesHumansLigationLiverMaleMatrix Metalloproteinase 2RatsRats, Sprague-DawleySmad2 ProteinTretinoinUrsodeoxycholic AcidConceptsBile duct ligationBile salt pool sizeLX-2 cellsUrsodeoxycholic acidHepatic stellate cellsRetinoic acidLiver fibrosisStellate cellsPhosphate-buffered salineCommon bile duct ligationMale Sprague-Dawley ratsPrimary human hepatic stellate cellsTumor necrosis factor αBile duct-ligated ratsHuman hepatic stellate cellsBile duct proliferationHuman hepatocytesLiver hydroxyproline contentNecrosis factor αSprague-Dawley ratsAcute promyelocytic leukemiaΑ-SMA expressionDuct-ligated ratsSmooth muscle actinMatrix metalloproteinase-2
2008
ATP8B1 Deficiency Disrupts the Bile Canalicular Membrane Bilayer Structure in Hepatocytes, But FXR Expression and Activity Are Maintained
Cai S, Gautam S, Nguyen T, Soroka CJ, Rahner C, Boyer JL. ATP8B1 Deficiency Disrupts the Bile Canalicular Membrane Bilayer Structure in Hepatocytes, But FXR Expression and Activity Are Maintained. Gastroenterology 2008, 136: 1060-1069.e4. PMID: 19027009, PMCID: PMC3439851, DOI: 10.1053/j.gastro.2008.10.025.Peer-Reviewed Original ResearchMeSH Keywords4-Chloro-7-nitrobenzofurazanAdenosine TriphosphatasesAnimalsATP Binding Cassette Transporter, Subfamily B, Member 11ATP-Binding Cassette TransportersBile CanaliculiCaco-2 CellsChenodeoxycholic AcidDNA-Binding ProteinsGastrointestinal AgentsGene ExpressionHepatocytesHumansMultidrug Resistance-Associated Protein 2PhosphatidylserinesPhospholipid Transfer ProteinsRatsReceptors, Cytoplasmic and NuclearRNA, Small InterferingTranscription FactorsTransfectionConceptsAminophospholipid flippaseMessenger RNAMembrane bilayer structureCanalicular membraneFarnesoid X receptorRat hepatocytesSmall heterodimer partnerMembrane transportersNBD-phosphatidylserineHeterodimer partnerDeficiency disruptsLuminal accumulationMembrane disruptionRNAConflicting hypothesesRat cellsFlippaseProtein levelsProtein expressionX receptorExpressionBSEP functionATP8B1CellsMembrane
2001
Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat
Lee J, Azzaroli F, Wang L, Soroka C, Gigliozzi A, Setchell K, Kramer W, Boyer J. Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat. Gastroenterology 2001, 121: 1473-1484. PMID: 11729126, DOI: 10.1053/gast.2001.29608.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsBile Acids and SaltsCarrier ProteinsCholestasisCommon Bile DuctFluorescent Antibody TechniqueKidneyLigationLiverMaleMicrovilliMitochondrial ProteinsOrganic Anion Transporters, Sodium-DependentRatsRats, Sprague-DawleyRibosomal ProteinsRNA, MessengerSaccharomyces cerevisiae ProteinsSymportersConceptsBile salt excretionCommon bile duct ligationBile salt transportersBile duct ligationSalt excretionObstructive cholestasisSalt transportersDuct ligationCommon bile duct obstructionKidney 14 daysBile duct obstructionBile salt transport proteinsSerum bile saltsBrush border membrane vesiclesProtein 2 expressionBile salt transportSodium-dependent uptakeExtrahepatic pathwaysLiver injuryDuct obstructionTissue immunofluorescenceBorder membrane vesiclesTransporter messenger RNAExtrahepatic tissuesTotal liverCl−-dependent secretory mechanisms in isolated rat bile duct epithelial units
Singh S, Mennone A, Gigliozzi A, Fraioli F, Boyer J. Cl−-dependent secretory mechanisms in isolated rat bile duct epithelial units. AJP Gastrointestinal And Liver Physiology 2001, 281: g438-g446. PMID: 11447024, DOI: 10.1152/ajpgi.2001.281.2.g438.Peer-Reviewed Original ResearchMeSH KeywordsAmmonium ChlorideAnimalsBariumBicarbonatesBile Ducts, IntrahepaticBumetanideCarbon DioxideCarrier ProteinsCell PolarityCells, CulturedChloridesColforsinEpithelial CellsHydrogen-Ion ConcentrationIon TransportMaleModels, BiologicalRatsRats, Sprague-DawleySodiumSodium-Potassium-Chloride SymportersConceptsCO2/HCOFluid secretionCotransport activityIntrahepatic bile duct epitheliumBile duct epitheliumDependent fluid secretionHigh intracellular Cl(-) concentrationIntracellular Cl- concentrationBile duct unitsApical Cl(-) secretionNH entryInitial acidification rateIntracellular cAMP concentrationNH4Cl exposureDuct epitheliumInhibitor bumetanideChannel inhibitorsCl(-) secretionCanalicular bileDuct unitsSecretionDependent secretionSecretory mechanismBumetanideForskolinCellular localization and up‐regulation of multidrug resistance–associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver
Soroka C, Lee J, Azzaroli F, Boyer J. Cellular localization and up‐regulation of multidrug resistance–associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatology 2001, 33: 783-791. PMID: 11283840, DOI: 10.1053/jhep.2001.23501.Peer-Reviewed Original ResearchConceptsObstructive cholestasisMultidrug resistance-associated protein 3Bile duct-ligated animalsMultidrug resistanceToxic bile acidsModel of cholestasisDuct-ligated animalsExpression of MRP3Intensity of stainingHepatocytes of liverWestern blot analysisBile ductHepatic expressionCentral veinCholestasisMRP3 expressionNormal liverBile acidsPericentral regionsIndirect immunofluorescenceProtein 3Days postligationMRP3Mrp2 proteinLiverRole of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes
Mennone A, Biemesderfer D, Negoianu D, Yang C, Abbiati T, Schultheis P, Shull G, Aronson P, Boyer J. Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes. AJP Gastrointestinal And Liver Physiology 2001, 280: g247-g254. PMID: 11208547, DOI: 10.1152/ajpgi.2001.280.2.g247.Peer-Reviewed Original Research
2000
Molecular identification and functional characterization of Mdr1a in rat cholangiocytes
Gigliozzi A, Fraioli F, Sundaram P, Lee J, Mennone A, Alvaro D, Boyer J. Molecular identification and functional characterization of Mdr1a in rat cholangiocytes. Gastroenterology 2000, 119: 1113-1122. PMID: 11040198, DOI: 10.1053/gast.2000.18156.Peer-Reviewed Original ResearchMeSH KeywordsAcridinesAnimalsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1ATP-Binding Cassette TransportersBile DuctsCell DivisionCell MembraneCytosolDrug Resistance, MultipleIn Vitro TechniquesIsoquinolinesKineticsMaleMicroscopy, ConfocalRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionRhodamine 123RNA, MessengerTetrahydroisoquinolinesTranscription, GeneticVanadatesVerapamilConceptsCholangiocyte cell linePlasma membrane proteinsRat cholangiocyte cell lineCell linesCytosolic domainMembrane proteinsRhodamine 123Functional characterizationGene productsRNA transcriptsMolecular identificationMembrane subfractionsPair fragmentWestern blot analysisWestern analysisApical membraneFunctional assaysFunctional evidenceBlot analysisConfocal microscopyP-glycoprotein inhibitor verapamilRat cholangiocytesLipophilic xenobioticsReverse transcription-polymerase chain reactionDose-dependent mannerATP-dependent GSH and glutathioneS-conjugate transport in skate liver: role of an Mrp functional homologue
Rebbeor J, Connolly G, Henson J, Boyer J, Ballatori N. ATP-dependent GSH and glutathioneS-conjugate transport in skate liver: role of an Mrp functional homologue. AJP Gastrointestinal And Liver Physiology 2000, 279: g417-g425. PMID: 10915652, DOI: 10.1152/ajpgi.2000.279.2.g417.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAnion Transport ProteinsAnionsATP-Binding Cassette TransportersBileBiological TransportCarrier ProteinsCell MembraneEnzyme InhibitorsGlutathioneLiverMaleOxidation-ReductionProtein BindingRatsRats, Sprague-DawleySkates, FishSubstrate SpecificityTaurocholic AcidTritiumConceptsATP-dependent transportLiver membrane vesiclesATP-dependent GSH transportMembrane vesiclesTransport activityATP-independent mechanismGlutathione-conjugate transportFunctional homologueMammalian cellsDNP-SG uptakePlasma membraneHomologous proteinsSkate liverGSH transportLow-affinity pathwayLittle skateMRP familyMultidrug resistance-associated protein 1GSH effluxFunctional assaysProtein 1First direct evidenceProtein bandsDirect evidenceHomologuesExpression of the bile salt export pump is maintained after chronic cholestasis in the rat
Lee J, Trauner M, Soroka C, Stieger B, Meier P, Boyer J. Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology 2000, 118: 163-172. PMID: 10611165, DOI: 10.1016/s0016-5085(00)70425-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily B, Member 11ATP-Binding Cassette TransportersBile Acids and SaltsBile DuctsCarrier ProteinsCholestasisChronic DiseaseDrug Resistance, MultipleEthinyl EstradiolLigationLipopolysaccharidesMembrane ProteinsMultidrug Resistance-Associated ProteinsOrganic Anion Transporters, Sodium-DependentRatsRats, Sprague-DawleyRNA, MessengerSymporters
1999
Carrier-mediated uptake of lucifer yellow in skate and rat hepatocytes: a fluid-phase marker revisited
Ballatori N, Hager D, Nundy S, Miller D, Boyer J. Carrier-mediated uptake of lucifer yellow in skate and rat hepatocytes: a fluid-phase marker revisited. American Journal Of Physiology 1999, 277: g896-g904. PMID: 10516157, DOI: 10.1152/ajpgi.1999.277.4.g896.Peer-Reviewed Original ResearchCanalicular Export Pumps Traffic with Polymeric Immunoglobulin A Receptor on the Same Microtubule-associated Vesicle in Rat Liver*
Soroka C, Pate M, Boyer J. Canalicular Export Pumps Traffic with Polymeric Immunoglobulin A Receptor on the Same Microtubule-associated Vesicle in Rat Liver*. Journal Of Biological Chemistry 1999, 274: 26416-26424. PMID: 10473600, DOI: 10.1074/jbc.274.37.26416.Peer-Reviewed Original ResearchConceptsApical membrane proteinsMembrane proteinsMicrotubule-associated vesiclesSite of functionMembrane transport proteinsMembrane-bound vesiclesNon-hydrolyzable nucleotidesReceptor trafficMicrotubule motorsTransport proteinsIntermediate chainEssential pathwayPolymeric immunoglobulinsSame vesiclesTranscytotic vesiclesMultidrug resistance protein 2Protein 2Immunoelectron microscopyVesiclesMicrotubulesProteinVesicular transcytosisPathwayRat hepatocytesCanalicular exportVasoactive intestinal polypeptide is a potent regulator of bile secretion from rat cholangiocytes
Cho W, Boyer J. Vasoactive intestinal polypeptide is a potent regulator of bile secretion from rat cholangiocytes. Gastroenterology 1999, 117: 420-428. PMID: 10419925, DOI: 10.1053/gast.1999.0029900420.Peer-Reviewed Original ResearchConceptsBile duct unitsEffect of VIPBile flowBile secretionDuct unitsIntestinal polypeptideFluid secretionBile duct-ligated ratsBile salt outputVasoactive intestinal polypeptideHepatocyte coupletsDose-dependent increaseDuct-ligated ratsBile pHVIP antagonistSite of actionSubstance PSecretory responseVIP responsesReceptor inhibitorsCAMP-independent pathwayBicarbonate secretionPotent stimulantSalt outputAbstractTextCharacterization of ion transport mechanisms involved in bombesin-stimulated biliary secretion in rat cholangiocytes
Cho W, Boyer J. Characterization of ion transport mechanisms involved in bombesin-stimulated biliary secretion in rat cholangiocytes. Journal Of Hepatology 1999, 30: 1045-1051. PMID: 10406182, DOI: 10.1016/s0168-8278(99)80258-x.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAcetazolamideAnimalsBarium CompoundsBileBile DuctsBombesinCarbonic Anhydrase InhibitorsChloride ChannelsChloridesIn Vitro TechniquesIon TransportMaleMicroscopy, VideoNitrobenzoatesPotassium ChannelsRatsRats, Sprague-DawleyTetraethylammoniumHepatic sequestration and modulation of the canalicular transport of the organic cation, daunorubicin, in the rat
Hayes J, Soroka C, Rios‐Velez L, Boyer J. Hepatic sequestration and modulation of the canalicular transport of the organic cation, daunorubicin, in the rat. Hepatology 1999, 29: 483-493. PMID: 9918926, DOI: 10.1002/hep.510290216.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Bacterial AgentsAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1BileBile CanaliculiBiological TransportBucladesineCationsChloroquineDaunorubicinKineticsLiverMacrolidesMaleMitochondrial ProteinsNocodazoleRatsRats, WistarRibosomal ProteinsSaccharomyces cerevisiae ProteinsTaurocholic AcidVerapamilConceptsBiliary excretionCoadministration of verapamilInhibitors of MDR1Rat hepatocyte coupletsBiliary recoveryDose administeredHepatic sequestrationTR- mutant ratsTherapeutic agentsExcretionDaunorubicinPericanalicular regionHepatocyte coupletsCanalicular transportRat liverBafilomycin ATaurocholateRatsIPRLIntracellular acidic compartmentsCellular localizationMicrotubule destabilizerConfocal microscopyIRHCPattern of distributionModulation of protein kinase C by taurolithocholic acid in isolated rat hepatocytes
Beuers U, Probst I, Soroka C, Boyer J, Kullak‐Ublick G, Paumgartner G. Modulation of protein kinase C by taurolithocholic acid in isolated rat hepatocytes. Hepatology 1999, 29: 477-482. PMID: 9918925, DOI: 10.1002/hep.510290227.Peer-Reviewed Original Research
1998
Nitric oxide and guanosine 3′,5′‐cyclic monophosphate stimulate bile secretion in isolated rat hepatocyte couplets, but not in isolated bile duct units
Trauner M, Mennone A, Gigliozzi A, Fraioli F, Boyer J. Nitric oxide and guanosine 3′,5′‐cyclic monophosphate stimulate bile secretion in isolated rat hepatocyte couplets, but not in isolated bile duct units. Hepatology 1998, 28: 1621-1628. PMID: 9828227, DOI: 10.1002/hep.510280623.Peer-Reviewed Original ResearchConceptsDuctular bile secretionBile secretionBile duct unitsNitric oxideRat hepatocyte coupletsExchanger activityNO synthesisCl-/HCO3Bile acid-independent bile flowCell-permeant cGMP analogDuct unitsEndogenous NO synthesisHepatocyte coupletsEffect of NOCell-permeant cAMP analogsLevel of hepatocytesCyclic monophosphateHepatic NO synthesisRemoval of HCO3Canalicular bile secretionNG-monomethylBile flowCholeretic effectDuctular luminaL-arginineIntracellular pH regulation in bombesin-stimulated secretion in isolated bile duct units from rat liver
Cho W, Mennone A, Boyer J. Intracellular pH regulation in bombesin-stimulated secretion in isolated bile duct units from rat liver. American Journal Of Physiology 1998, 275: g1028-g1036. PMID: 9815033, DOI: 10.1152/ajpgi.1998.275.5.g1028.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntiportersBicarbonatesBile Ducts, IntrahepaticBombesinCarrier ProteinsChloride-Bicarbonate AntiportersChloridesFluoresceinsFluorescent DyesHEPESHydrogen-Ion ConcentrationIn Vitro TechniquesMaleModels, BiologicalRatsRats, Sprague-DawleySodiumSodium-Bicarbonate SymportersSodium-Hydrogen ExchangersConceptsHCO-3 secretionBile duct unitsDuct unitsAcid-extruding mechanismsEffect of bombesinRat liverCl-/HCOBombesin-stimulated secretionRegulation of intracellularBiliary secretionNormal rat liverBombesinCholangiocytesSecretionUnderlying mechanismLiverBasalPH regulationCounterregulatoryNeuropeptidesExchange activityActivity