2022
Molecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes
Rodrigues MA, Gomes DA, Fiorotto R, Guerra MT, Weerachayaphorn J, Bo T, Sessa WC, Strazzabosco M, Nathanson MH. Molecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes. Hepatology Communications 2022, 6: 2748-2764. PMID: 35852334, PMCID: PMC9512452, DOI: 10.1002/hep4.2042.Peer-Reviewed Original ResearchConceptsLipid raftsCaveolin-1Intact lipid raftsType 3 inositol trisphosphate receptorApical regionC-terminal amino acidsTrisphosphate receptor type 3Madin-Darby canine kidney cellsCanine kidney cellsFluorescence microscopy techniquesInositol trisphosphate receptorApical localizationTrisphosphate receptorHeavy chain 9Molecular determinantsChemical disruptionAmino acidsITPR3RaftsKidney cellsIntracellular CaFinal common eventReceptor type 3Release channelMYH9Morphological alteration of the pancreatic islet in ovariectomized rats fed a high-fat high-fructose diet
Chansela P, Potip B, Weerachayaphorn J, Kangwanrangsan N, Chukijrungroat N, Saengsirisuwan V. Morphological alteration of the pancreatic islet in ovariectomized rats fed a high-fat high-fructose diet. Histochemistry And Cell Biology 2022, 157: 427-442. PMID: 35037128, DOI: 10.1007/s00418-021-02062-0.Peer-Reviewed Original ResearchConceptsHigh-fat high-fructose dietHigh-fructose dietEstrogen deficiencyInsulin resistancePancreatic isletsOVX ratsWhole-body insulin resistanceExcessive caloric intakeElevated plasma glucoseInsulin-resistant statesΒ-cell dysfunctionInsulin-producing β-cellsDiabetes coexistsEstrogen replacementInsulin levelsOvariectomized ratsDiabetic statePlasma glucoseDisease progressionHistological changesPancreatic morphologyCaloric intakeFat accumulationGlucagon-producing α-cellsImmunohistochemical staining
2020
Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis
Takeuchi M, Vidigal PT, Guerra MT, Hundt MA, Robert ME, Olave-Martinez M, Aoki S, Khamphaya T, Kersten R, Kruglov E, de la Rosa Rodriguez R, Banales JM, Nathanson MH, Weerachayaphorn J. Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis. Gut 2020, 70: 342-356. PMID: 33214166, PMCID: PMC7906004, DOI: 10.1136/gutjnl-2020-322540.Peer-Reviewed Original ResearchConceptsBile ductCholestatic changesLimited treatment optionsPresence of cholestasisAbility of neutrophilsLife-threatening diseaseNew therapeutic targetsHuman bile ductIntracellular calcium channelsAlcoholic hepatitisLiver biopsyControl neutrophilsPathological findingsHepatocellular damageHistological findingsTreatment optionsCell adhesion moleculeHistological parametersDisease altersITPR3 expressionTherapeutic targetAnimal modelsCalcium channelsNeutrophilsPatientsType 3 Inositol 1,4,5‐Trisphosphate Receptor Is Increased and Enhances Malignant Properties in Cholangiocarcinoma
Ueasilamongkol P, Khamphaya T, Guerra MT, Rodrigues M, Gomes DA, Kong Y, Wei W, Jain D, Trampert DC, Ananthanarayanan M, Banales JM, Roberts LR, Farshidfar F, Nathanson MH, Weerachayaphorn J. Type 3 Inositol 1,4,5‐Trisphosphate Receptor Is Increased and Enhances Malignant Properties in Cholangiocarcinoma. Hepatology 2020, 71: 583-599. PMID: 31251815, PMCID: PMC6934938, DOI: 10.1002/hep.30839.Peer-Reviewed Original ResearchConceptsType 3 inositolCCA cellsIntracellular calcium ionsPathogenesis of malignanciesCCA cell linesCommon malignancyPoor prognosisTrisphosphate receptorMalignant featuresMitochondrial CaITPR3 expressionCholangiocarcinomaRegions of ERMalignant propertiesCCA samplesCell proliferationCholangiocytesEndoplasmic reticulumType of tissueMalignancyCell linesITPR3PathogenesisCell deathCell migration
2019
Effects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes
Franca A, Filho A, Guerra MT, Weerachayaphorn J, dos Santos M, Njei B, Robert M, Lima C, Vidigal P, Banales JM, Ananthanarayanan M, Leite MF, Nathanson MH. Effects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes. Hepatology 2019, 69: 817-830. PMID: 30141207, PMCID: PMC6351171, DOI: 10.1002/hep.30228.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Alcoholic hepatitisEffect of endotoxinBile duct cellsNF-κBInhibition of TLR4Human cholangiocytesStimulation of TLR4Duct cellsSevere alcoholic hepatitisCholestasis of sepsisForms of cholestasisNF-κB subunitsP65/p50Trisphosphate receptorReceptor 4Clinical conditionsBicarbonate secretionHepatocellular changesITPR3 expressionCholestasisType 3 inositolLPS receptorAgonist stimulusSepsis
2018
Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5‐trisphosphate receptor
Khamphaya T, Chukijrungroat N, Saengsirisuwan V, Mitchell‐Richards K, Robert ME, Mennone A, Ananthanarayanan M, Nathanson MH, Weerachayaphorn J. Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5‐trisphosphate receptor. Hepatology 2018, 67: 560-574. PMID: 29023819, PMCID: PMC5893412, DOI: 10.1002/hep.29588.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseImpaired liver regenerationNonalcoholic steatohepatitisLiver regenerationHuh7 cellsLiver diseaseEffect of NAFLDPrevalent liver diseaseFatty liver diseaseC-JunHigh-fructose dietLiver biopsy specimensCell proliferationCalcium signalingHepG2 cellsLiver of ratsCell nuclear antigenCalcium release channelSimple steatosisLiver biopsyFatty liverTrisphosphate receptorBiopsy specimensRat modelType II inositol
2017
Type 2 inositol trisphosphate receptor gene expression in hepatocytes is regulated by cyclic AMP
Kruglov E, Ananthanarayanan M, Sousa P, Weerachayaphorn J, Guerra MT, Nathanson MH. Type 2 inositol trisphosphate receptor gene expression in hepatocytes is regulated by cyclic AMP. Biochemical And Biophysical Research Communications 2017, 486: 659-664. PMID: 28327356, PMCID: PMC5421629, DOI: 10.1016/j.bbrc.2017.03.086.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsBinding SitesColforsinCREB-Binding ProteinCyclic AMPDactinomycinFastingGene Expression RegulationHep G2 CellsHepatocytesHumansInositol 1,4,5-Trisphosphate ReceptorsMaleMutationPrimary Cell CulturePromoter Regions, GeneticProtein BindingRatsRats, Sprague-DawleyResponse ElementsRNA, MessengerSignal TransductionThionucleotidesConceptsPost-translational modificationsRecruitment of CREBAdenylyl cyclase 6Transcriptional regulationType 2 inositolGene expressionPromoter activityTrisphosphate receptorCyclase 6CRE elementTreatment of hepatocytesReceptor gene expressionAC isoformsCREBHormonal regulationProtein levelsIntracellular CaD. AnalysisPromoterRelease channelExpressionCyclic AMPIP3R2RegulationRat hepatocytes
2016
Effects of andrographolide on intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats
Khamphaya T, Chansela P, Piyachaturawat P, Suksamrarn A, Nathanson MH, Weerachayaphorn J. Effects of andrographolide on intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats. European Journal Of Pharmacology 2016, 789: 254-264. PMID: 27475677, PMCID: PMC10804355, DOI: 10.1016/j.ejphar.2016.07.032.Peer-Reviewed Original ResearchConceptsCholestatic liver diseaseLiver diseaseIntrahepatic cholestasisLiver injuryProtective effectHepatic stellate cell activationAcute intrahepatic cholestasisAlpha-smooth muscle actinCholestatic liver injuryBile duct proliferationSerum alanine aminotransferaseNF-κB expressionSingle intraperitoneal injectionEffects of andrographolidePromising therapeutic optionEffective therapeutic approachPotent protective propertiesNuclear factor kappaStellate cell activationANIT injectionDuct proliferationTherapeutic optionsHepatoprotective effectPeriductular fibrosisAlternative therapies
2015
Nuclear Factor, Erythroid 2-Like 2 Regulates Expression of Type 3 Inositol 1,4,5-Trisphosphate Receptor and Calcium Signaling in Cholangiocytes
Weerachayaphorn J, Amaya MJ, Spirli C, Chansela P, Mitchell-Richards KA, Ananthanarayanan M, Nathanson MH. Nuclear Factor, Erythroid 2-Like 2 Regulates Expression of Type 3 Inositol 1,4,5-Trisphosphate Receptor and Calcium Signaling in Cholangiocytes. Gastroenterology 2015, 149: 211-222.e10. PMID: 25796361, PMCID: PMC4478166, DOI: 10.1053/j.gastro.2015.03.014.Peer-Reviewed Original ResearchConceptsBile ductBile duct unitsCholestatic disordersOxidative stressCalcium signalingNuclear factorMouse cholangiocytesDuct unitsReduced calcium signalingIntrahepatic bile ductsLevels of Nrf2Cholangiocyte cellsKnockdown of Nrf2Activation of Nrf2Intracellular calcium release channelsTranscription factor Nrf2Binding of Nrf2Calcium release channelPolymerase chain reaction analysisBiliary diseaseTrisphosphate receptorControl ratsLiver disordersBicarbonate secretionChain reaction analysis
2013
Deleterious effect of oltipraz on extrahepatic cholestasis in bile duct-ligated mice
Weerachayaphorn J, Luo Y, Mennone A, Soroka CJ, Harry K, Boyer JL. Deleterious effect of oltipraz on extrahepatic cholestasis in bile duct-ligated mice. Journal Of Hepatology 2013, 60: 160-166. PMID: 23978715, PMCID: PMC4054607, DOI: 10.1016/j.jhep.2013.08.015.Peer-Reviewed Original ResearchConceptsBile duct ligationBDL miceLiver injuryControl miceBile duct-ligated miceBile flow rateBile duct obstructionHepato-protective effectsSmooth muscle actin expressionLiver function markersSevere liver damageBile acid-independent flowHigher bile flowMatrix metalloproteinases-9Hepatic stellate cellsCancer preventive agentsMuscle actin expressionPromising cancer-preventive agentBiliary pressureSerum aminotransferasesLiver histologyBDL groupPhase II detoxificationPortal fibroblastsProfibrogenic genesAlleviative effect of andrographolide on alpha‐naphthylisothiocyanate‐induced cholestatic liver injury in rats
Khamphaya T, Piyachaturawat P, Weerachayaphorn J. Alleviative effect of andrographolide on alpha‐naphthylisothiocyanate‐induced cholestatic liver injury in rats. The FASEB Journal 2013, 27: 1161.2-1161.2. DOI: 10.1096/fasebj.27.1_supplement.1161.2.Peer-Reviewed Original ResearchLiver injuryMonocyte chemoattractant protein-1Severe liver inflammationCholestatic liver damageCholestatic liver injuryBile duct proliferationChemoattractant protein-1Tumor necrosis factorPotential therapeutic actionNF-kB signalingGamma-glutamyl transpeptidaseLiver inflammationSerum aminotransferasesLiver failureLiver diseaseDuct proliferationLiver damageHepatoprotective effectMajor active compoundNecrosis factorHepatic accumulationNF-kBAndrographolide pretreatmentANITBile acids
2012
Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine
Weerachayaphorn J, Mennone A, Soroka CJ, Harry K, Hagey LR, Kensler TW, Boyer JL. Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine. AJP Gastrointestinal And Liver Physiology 2012, 302: g925-g936. PMID: 22345550, PMCID: PMC3362073, DOI: 10.1152/ajpgi.00263.2011.Peer-Reviewed Original ResearchConceptsBile duct ligationBile acid homeostasisBile acid synthesisBile acidsLiver injuryAcid homeostasisMRNA expressionWild-type control miceBile acid transporter expressionCYP3A11 mRNA expressionBile salt export pumpBiliary bile acidsDeletion of Nrf2Bile acid reabsorptionRole of Nrf2Factor 2Bile acid hydroxylationPregnane X receptorBDL miceExpression of regulatorsControl miceDuct ligationNrf2 resultsBile secretionHepatobiliary transporters
2010
Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression
Xu S, Weerachayaphorn J, Cai SY, Soroka CJ, Boyer JL. Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression. AJP Gastrointestinal And Liver Physiology 2010, 299: g126-g135. PMID: 20395535, PMCID: PMC2904108, DOI: 10.1152/ajpgi.00522.2010.Peer-Reviewed Original ResearchMeSH Keywords5' Flanking RegionAnimalsAryl Hydrocarbon Receptor Nuclear TranslocatorBase SequenceBasic Helix-Loop-Helix Transcription FactorsBinding SitesButylaminesChromatin ImmunoprecipitationDose-Response Relationship, DrugElectrophoretic Mobility Shift AssayGenes, ReporterHep G2 CellsHepatocytesHumansMethylcholanthreneMiceMolecular Sequence DataMultidrug Resistance-Associated ProteinsMutationNF-E2-Related Factor 2Polychlorinated DibenzodioxinsPromoter Regions, GeneticPyrazinesReceptors, Aryl HydrocarbonResponse ElementsRNA InterferenceRNA, MessengerThionesThiophenesTime FactorsTransfectionConceptsMRP4 expressionAryl hydrocarbon receptorNF-E2Renal proximal tubule epitheliumCholestatic liver injuryHydrocarbon receptorXenobiotic response elementProximal tubule epitheliumMultidrug resistance protein 4Factor 2Bile salt conjugatesNuclear receptor agonistsLiver injuryPromoter activityReceptor agonistTherapeutic benefitAnimal modelsNrf2 activatorsTubule epitheliumHuman MRP4Conjugated steroidsNuclear factorAdaptive upregulationOxidative stressLuciferase reporter
2009
Nuclear factor erythroid 2–related factor 2 is a positive regulator of human bile salt export pump expression
Weerachayaphorn J, Cai S, Soroka CJ, Boyer JL. Nuclear factor erythroid 2–related factor 2 is a positive regulator of human bile salt export pump expression. Hepatology 2009, 50: 1588-1596. PMID: 19821532, PMCID: PMC3013376, DOI: 10.1002/hep.23151.Peer-Reviewed Original ResearchMeSH KeywordsATP Binding Cassette Transporter, Subfamily B, Member 11ATP-Binding Cassette TransportersBase SequenceHep G2 CellsHepatocytesHumansMaf Transcription FactorsMolecular Sequence DataNF-E2-Related Factor 2PyrazinesReverse Transcriptase InhibitorsRNA, MessengerSignal TransductionThionesThiophenesConceptsBile salt export pumpCholestatic liver injuryPositive transcriptional regulatorElectrophoretic mobility shift assaysHepG2 cellsBSEP expressionChromatin immunoprecipitation assaysBSEP promoterMobility shift assaysAdditional transcriptional factorsProximal promoter regionBSEP promoter activitySmall interfering RNAsFactor 2Liver injuryNuclear factorAntioxidant responsive elementTranscriptional regulatorsNrf2 transcriptional activationTranscriptional activationPositive regulatorBile salt export pump expressionNuclear farnesoid X receptorImmunoprecipitation assaysShift assays
2007
Threonine-509 Is a Determinant of Apparent Affinity for Both Substrate and Cations in the Human Na+/Dicarboxylate Cotransporter †
Weerachayaphorn J, Pajor AM. Threonine-509 Is a Determinant of Apparent Affinity for Both Substrate and Cations in the Human Na+/Dicarboxylate Cotransporter †. Biochemistry 2007, 47: 1087-1093. PMID: 18161988, PMCID: PMC2570185, DOI: 10.1021/bi701417h.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsChlorocebus aethiopsCitric AcidCOS CellsDicarboxylic Acid TransportersGene ExpressionHumansKineticsMolecular Sequence DataMutationOrganic Anion Transporters, Sodium-DependentRabbitsRecombinant ProteinsSequence Homology, Amino AcidSodiumSubstrate SpecificitySuccinic AcidSymportersThreonineConceptsTransmembrane helix 7Functional differencesApparent affinityApparent sodium affinitySubstrate Binding SiteAmino acid differencesCitric acid cycleCitrate affinityHelix 7Substrate specificityPosition -509Rabbit sequenceIndividual residuesAcid cycleAcid differencesSimilar apparent affinitiesLoop regionIntermediate KmAmino acidsBinding sitesMutantsNaDC1SerineThreonineExhibit differencesIdentification of transport pathways for citric acid cycle intermediates in the human colon carcinoma cell line, Caco-2
Weerachayaphorn J, Pajor AM. Identification of transport pathways for citric acid cycle intermediates in the human colon carcinoma cell line, Caco-2. Biochimica Et Biophysica Acta 2007, 1778: 1051-1059. PMID: 18194662, PMCID: PMC2323910, DOI: 10.1016/j.bbamem.2007.12.013.Peer-Reviewed Original ResearchBiological TransportCaco-2 CellsCitratesCitric Acid CycleColonic NeoplasmsDicarboxylic Acid TransportersEpithelial CellsExtracellular SpaceGene Expression RegulationHumansIntracellular SpaceKineticsModels, BiologicalOrganic Anion TransportersOrganic Anion Transporters, Sodium-DependentPlasticsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSodiumSubstrate SpecificitySuccinatesSymportersTime FactorsTransfectionSodium-dependent Extracellular Accessibility of Lys-84 in the Sodium/Dicarboxylate Cotransporter*
Weerachayaphorn J, Pajor AM. Sodium-dependent Extracellular Accessibility of Lys-84 in the Sodium/Dicarboxylate Cotransporter*. Journal Of Biological Chemistry 2007, 282: 20213-20220. PMID: 17504760, PMCID: PMC2864014, DOI: 10.1074/jbc.m701113200.Peer-Reviewed Original ResearchConceptsLys-84Transmembrane helicesMTS inhibitionLarge-scale conformational changesTranslocation of substratesCysteine-specific reagentsTransmembrane helix 3SLC13 familyCitric acid cycle intermediatesExtracellular halfEpithelial cell lineExtracellular accessibilityHelix 3Transport cycleTrp-103Human retinal pigment epithelial cell lineAddition of substrateConformational changesLeu-111Conformational statesRetinal pigment epithelial cell lineSubstrate affinityReentrant loopAmino acidsGlu-101