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 channelMYH9
2020
Inositol 1,4,5 trisphosphate receptors in secretory epithelial cells of the gastrointestinal tract
Lemos F, Guerra M, de Fátima Leite M. Inositol 1,4,5 trisphosphate receptors in secretory epithelial cells of the gastrointestinal tract. Current Opinion In Physiology 2020, 17: 169-174. DOI: 10.1016/j.cophys.2020.08.003.Peer-Reviewed Original ResearchEpithelial cellsFatty liver diseaseIntracellular calcium signalingLiver diseaseAcute pancreatitisSecretory epithelial cellsPathophysiological roleGastrointestinal tractElectrolyte secretionSolid tumorsIntracellular Ca2Main intracellular Ca2Number of diseasesDiseaseCell proliferationCalcium signalingEnergy metabolismReceptorsMolecular mechanismsSubcellular localizationTrisphosphate receptorPhysiological functionsCellsInositol 1Ca2Type 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
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
2014
Post-translational Regulation of the Type III Inositol 1,4,5-Trisphosphate Receptor by miRNA-506*
Ananthanarayanan M, Banales JM, Guerra MT, Spirli C, Munoz-Garrido P, Mitchell-Richards K, Tafur D, Saez E, Nathanson MH. Post-translational Regulation of the Type III Inositol 1,4,5-Trisphosphate Receptor by miRNA-506*. Journal Of Biological Chemistry 2014, 290: 184-196. PMID: 25378392, PMCID: PMC4281721, DOI: 10.1074/jbc.m114.587030.Peer-Reviewed Original ResearchConceptsReporter activityMiR-506Trisphosphate receptorPost-translational regulationMiR-506 mimicsCell linesMiR-506 inhibitorEpigenetic regulationMiRNA regulationType III inositolFibrotic signatureMiR-506 expressionType III isoformCholangiocyte cell lineHEK293 cellsSitu hybridizationProtein levelsControl cellsInsP3R3H69 cellsRegulationSignalingExpressionCellsInositol
2011
Type 2 inositol 1,4,5‐trisphosphate receptor modulates bile salt export pump activity in rat hepatocytes
Kruglov EA, Gautam S, Guerra MT, Nathanson MH. Type 2 inositol 1,4,5‐trisphosphate receptor modulates bile salt export pump activity in rat hepatocytes. Hepatology 2011, 54: 1790-1799. PMID: 21748767, PMCID: PMC3205211, DOI: 10.1002/hep.24548.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter, Subfamily B, Member 11ATP-Binding Cassette TransportersBile Acids and SaltsBile CanaliculiCalciumCalcium SignalingCell Culture TechniquesCells, CulturedCholestasisCollagenDisease Models, AnimalHepatocytesInositol 1,4,5-Trisphosphate ReceptorsLipopolysaccharidesMaleProtein Processing, Post-TranslationalRatsRats, Sprague-DawleyConceptsBile salt secretionBSEP activityTrisphosphate receptorBile salt export pumpType II inositolSalt secretionPosttranslational regulationCell systemType 2 inositolCanalicular membraneCholesterol depletionIntrahepatic cholestasisConfocal immunofluorescenceFunctional polarityIntracellular calciumIsolated cell systemRat hepatocytesAnimal modelsSandwich cultureCollagen sandwich culturesPharmacologic inhibitionShort-term regulationCell membraneExport pumpSecretion
2010
The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma
Shibao K, Fiedler MJ, Nagata J, Minagawa N, Hirata K, Nakayama Y, Iwakiri Y, Nathanson MH, Yamaguchi K. The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma. Cell Calcium 2010, 48: 315-323. PMID: 21075448, PMCID: PMC3572849, DOI: 10.1016/j.ceca.2010.09.005.Peer-Reviewed Original ResearchConceptsTrisphosphate receptorCaco-2 colon cancer cellsGain of expressionColorectal cancerColorectal carcinomaColon cancer cellsColon cancerType IIICellular functionsInhibition of apoptosisType III inositolLymph node metastasisDepth of invasionNormal colorectal mucosaShRNA knockdownMargin of tumorDevelopment of diseaseExpression levelsLiver metastasesCell proliferationNode metastasisTNM stageApoptosisColorectal mucosaIsoformsPolycystin-2 Activation by Inositol 1,4,5-Trisphosphate-induced Ca2+ Release Requires Its Direct Association with the Inositol 1,4,5-Trisphosphate Receptor in a Signaling Microdomain*
Sammels E, Devogelaere B, Mekahli D, Bultynck G, Missiaen L, Parys JB, Cai Y, Somlo S, De Smedt H. Polycystin-2 Activation by Inositol 1,4,5-Trisphosphate-induced Ca2+ Release Requires Its Direct Association with the Inositol 1,4,5-Trisphosphate Receptor in a Signaling Microdomain*. Journal Of Biological Chemistry 2010, 285: 18794-18805. PMID: 20375013, PMCID: PMC2881802, DOI: 10.1074/jbc.m109.090662.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseasePolycystic kidney diseaseKidney diseaseGlutathione S-transferase pulldown experimentsEndoplasmic reticulumTrisphosphate receptorAgonist-induced intracellularTerminal ligand-binding domainMouse renal epithelial cellsTerminal cytoplasmic tailLigand-binding domainAdenoviral expression systemRenal epithelial cellsSignaling microdomainPathological mutantsPulldown experimentsTrisphosphate-induced Ca2Cytoplasmic tailAcidic clusterPolycystin-1Polycystin-2TRPP2Epithelial cellsExpression system
2007
Molecular basis for calcium signaling in hepatic stellate cells
Kruglov EA, Correa PR, Arora G, Yu J, Nathanson MH, Dranoff JA. Molecular basis for calcium signaling in hepatic stellate cells. AJP Gastrointestinal And Liver Physiology 2007, 292: g975-g982. PMID: 17204544, DOI: 10.1152/ajpgi.00401.2006.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAdenosine TriphosphateAnimalsCalcium SignalingCalreticulinCell NucleusCell ShapeCell Surface ExtensionsCells, CulturedEndoplasmic ReticulumInositol 1,4,5-Trisphosphate ReceptorsLiverLiver CirrhosisMaleMicroscopy, ConfocalMicroscopy, VideoRatsRats, Sprague-DawleyReceptors, Purinergic P2RNA, MessengerTime FactorsConceptsHepatic stellate cellsCell extensionsLipid-storing cellsSubcellular organizationLiver fibrosisMolecular basisStellate cellsSubcellular signalingTrisphosphate receptorChronic liver failureProgressive liver fibrosisSufficient machineryExtracellular ATPMyofibroblastic transdifferentiationOrgan fibrosisLiver failureP2Y receptorsHealthy liverATPLocal controlCellsCritical stepLocal applicationImportant mediatorFibrosis
2005
Calcium release from ryanodine receptors in the nucleoplasmic reticulum
Marius P, Guerra MT, Nathanson MH, Ehrlich BE, Leite MF. Calcium release from ryanodine receptors in the nucleoplasmic reticulum. Cell Calcium 2005, 39: 65-73. PMID: 16289270, DOI: 10.1016/j.ceca.2005.09.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCalcium ChannelsCalcium SignalingCell LineCell NucleusCytoplasmDantroleneEndoplasmic ReticulumInositol 1,4,5-TrisphosphateInositol 1,4,5-Trisphosphate ReceptorsMiceMicroscopy, FluorescenceMuscle, SkeletalNuclear EnvelopeReceptors, Cytoplasmic and NuclearRyanodine Receptor Calcium Release ChannelConceptsNucleoplasmic reticulumNuclear envelopeRyanodine receptorType 1 RyRGene transcriptionC2C12 cellsTrisphosphate receptorIntranuclear eventsCell typesReticulumDNA synthesisCell linesCell functionReticular networkSkeletal muscleRyR inhibitor dantroleneDiscrete regionsTwo-photon photoreleaseRyRsReceptorsNucleusCellsTranscriptionThe Anti-apoptotic Protein Mcl-1 Inhibits Mitochondrial Ca2+ Signals*
Minagawa N, Kruglov EA, Dranoff JA, Robert ME, Gores GJ, Nathanson MH. The Anti-apoptotic Protein Mcl-1 Inhibits Mitochondrial Ca2+ Signals*. Journal Of Biological Chemistry 2005, 280: 33637-33644. PMID: 16027162, DOI: 10.1074/jbc.m503210200.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAniline CompoundsAntibodies, MonoclonalApoptosisBile Duct NeoplasmsCalcium SignalingCarbocyaninesCell LineCell Line, TumorCell NucleusFluorescent Antibody Technique, IndirectFluorescent DyesHeterocyclic Compounds, 3-RingHumansHydrazinesImmunohistochemistryMicroscopy, ConfocalMitochondriaModels, BiologicalMyeloid Cell Leukemia Sequence 1 ProteinNeoplasm ProteinsProto-Oncogene Proteins c-bcl-2Signal TransductionTissue DistributionXanthenesConceptsAnti-apoptotic proteinsMcl-1Mitochondrial Ca2Mcl-1 expressionApoptotic stimuliEndoplasmic reticulum Ca2Trisphosphate receptorCell growthNovel mechanismApoptosisMechanism of actionProteinExpressionDevelopment of neoplasiaCa2Reticulum Ca2CellsMitochondriaInositolRegulationPathwayMechanismSignalsReceptorsRegeneration
2004
Sphingosine-1-phosphate mediates calcium signaling in guinea pig enteroglial cells
Segura BJ, Zhang W, Xiao L, Turner D, Cowles RA, Logsdon C, Mulholland MW. Sphingosine-1-phosphate mediates calcium signaling in guinea pig enteroglial cells. Journal Of Surgical Research 2004, 116: 42-54. PMID: 14732348, DOI: 10.1016/s0022-4804(03)00281-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportCalciumCalcium ChannelsCalcium SignalingCulture TechniquesDose-Response Relationship, DrugDrug Administration ScheduleEnzyme ActivationGuinea PigsImmunohistochemistryInositol 1,4,5-Trisphosphate ReceptorsLysophospholipidsMyenteric PlexusNeurogliaPertussis ToxinReceptors, Cytoplasmic and NuclearReceptors, G-Protein-CoupledRNA, MessengerSphingolipidsSphingosineType C PhospholipasesConceptsSignal transduction cascadeEnteric nervous systemEnteric gliaLipid lysophosphatidic acidMajor cell typesRT-PCR analysisTransduction cascadeGlial cellsNervous systemEDG-1Trisphosphate receptorCalcium signalingLysophosphatidic acidCell typesExtracellular receptorsPhospholipase CEdg-3Enteric glial cellsBioactive lipidsEdg-5S1P effectsSphingomyelin metabolitesDigestive activityImmunocytochemical analysisEnteric neurons
2003
Regulation of calcium signals in the nucleus by a nucleoplasmic reticulum
Echevarría W, Leite MF, Guerra MT, Zipfel WR, Nathanson MH. Regulation of calcium signals in the nucleus by a nucleoplasmic reticulum. Nature Cell Biology 2003, 5: 440-446. PMID: 12717445, PMCID: PMC3572851, DOI: 10.1038/ncb980.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusCalciumCalcium ChannelsCalcium SignalingCell MembraneCell Nucleus StructuresCytosolEndoplasmic ReticulumEukaryotic CellsHumansInositol 1,4,5-TrisphosphateInositol 1,4,5-Trisphosphate ReceptorsMicroscopy, ConfocalNuclear EnvelopePhotochemistryProtein Kinase CProtein TransportReceptors, Cytoplasmic and NuclearTumor Cells, CulturedConceptsProtein kinase CNucleoplasmic reticulumCalcium signalsNuclear envelopeNuclear protein kinase CNuclear calcium signalsCytosolic protein kinase CGene transcriptionInduces translocationNuclear calcium storesPlasma membraneCytosolic calcium signalsSubnuclear regionsEndoplasmic reticulumSecond messengerKinase CTrisphosphate receptorCell growthReticulumNuclear componentsReticular networkPotential mechanismsCalcium storesRelease of calciumNucleusNuclear and cytosolic calcium are regulated independently
Leite MF, Thrower EC, Echevarria W, Koulen P, Hirata K, Bennett AM, Ehrlich BE, Nathanson MH. Nuclear and cytosolic calcium are regulated independently. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 2975-2980. PMID: 12606721, PMCID: PMC151451, DOI: 10.1073/pnas.0536590100.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateCalciumCalcium ChannelsCell LineCell MembraneCell NucleusCytosolDose-Response Relationship, DrugEndoplasmic ReticulumHumansImmunoblottingImmunohistochemistryInositol 1,4,5-Trisphosphate ReceptorsLipid BilayersMicroscopy, ConfocalProtein IsoformsReceptors, Cytoplasmic and NuclearSignal TransductionTime FactorsConceptsEndoplasmic reticulumImportant cellular processesType II isoformCellular processesCellular compartmentsGene transcriptionEnriched expressionNuclear calciumTrisphosphate receptorIndependent regulationCytosolLiver cell lineCell linesHepG2 liver cell lineSubcellular mechanismsReticulumNucleus resultsDependent processesCytosolic calciumNucleusTranscriptionType ISignalingIsoformsSimilar extent
2001
Regulation of Ins(1,4,5)P3 receptor isoforms by endogenous modulators
Thrower E, Hagar R, Ehrlich B. Regulation of Ins(1,4,5)P3 receptor isoforms by endogenous modulators. Trends In Pharmacological Sciences 2001, 22: 580-586. PMID: 11698102, DOI: 10.1016/s0165-6147(00)01809-5.Peer-Reviewed Original ResearchFunctional overlap of IP3- and cADP-ribose-sensitive calcium stores in guinea pig myenteric neurons
Turner D, Segura B, Cowles R, Zhang W, Mulholland M. Functional overlap of IP3- and cADP-ribose-sensitive calcium stores in guinea pig myenteric neurons. AJP Gastrointestinal And Liver Physiology 2001, 281: g208-g215. PMID: 11408274, DOI: 10.1152/ajpgi.2001.281.1.g208.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine Diphosphate RiboseAdenosine TriphosphateAnesthetics, LocalAnimalsBiological TransportCaffeineCalciumCalcium Channel BlockersCinnarizineCyclic ADP-RiboseDantroleneGuinea PigsInositol 1,4,5-TrisphosphateMicroinjectionsMuscle Relaxants, CentralMyenteric PlexusNeuronsPhosphodiesterase InhibitorsProcaineRyanodineConceptsMyenteric neuronsReceptor subtypesGuinea pig myenteric neuronsDifferent receptor subtypesMobilization of intracellularSuperfusion techniqueCalcium storesRyR antagonistSubsequent perfusionATP exposureNeuronsRyanodine receptorCADP-riboseAntagonistIntracellular microinjectionPerfusionMicroM ATPSubtypesRyRsIntracellularReceptorsTrisphosphate receptorCinnarizineSpecific ligandsMicroinjection
1999
Expression and subcellular localization of the ryanodine receptor in rat pancreatic acinar cells.
Leite MF, Dranoff JA, Gao L, Nathanson MH. Expression and subcellular localization of the ryanodine receptor in rat pancreatic acinar cells. Biochemical Journal 1999, 337 ( Pt 2): 305-9. PMID: 9882629, PMCID: PMC1219966, DOI: 10.1042/0264-6021:3370305.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsNon-excitable cell typesCell typesCell types resultsAcinar cellsNon-excitable cellsRyanodine receptorSubcellular localizationPolarized epitheliumReverse transcription-PCRRat pancreatic acinar cellsTrisphosphate receptorCo-ordinated releaseType 2 RyRExcitable cellsRelease pathwayTranscription-PCRPrincipal Ca2Release channelApical regionCytosolic Ca2CellsFundamental roleRyRsPropagation of Ca2
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