2018
Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways
Zacchia M, Tian X, Zona E, Alpern RJ, Preisig PA. Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways. Journal Of The American Society Of Nephrology 2018, 29: 1720-1730. PMID: 29678998, PMCID: PMC6054333, DOI: 10.1681/asn.2017121268.Peer-Reviewed Original ResearchMeSH KeywordsAcidsAmmonium ChlorideAnimalsCells, CulturedCitric AcidCSK Tyrosine-Protein KinaseDicarboxylic Acid TransportersEndothelin-1Epithelial CellsFocal Adhesion Kinase 2Kidney Tubules, ProximalMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3OpossumsOrganic Anion Transporters, Sodium-DependentPhosphorylationProto-Oncogene Proteins c-rafReceptor, Endothelin BRibosomal Protein S6 Kinases, 90-kDaSrc-Family KinasesTransfectionConceptsET-1/ETEndothelin-1Proximal tubulesCultured opossum kidney cellsAcid stimulationInhibition of Pyk2ET-1 stimulationRenal proximal tubulesNaDC-1Opossum kidney cellsCl loadingC-SrcPhosphorylation of Raf1Urine citratePyk2 knockdownEnd pointAcid loadApical NaERK1/2 pathwayStimulationMiceKidney cellsKidneyPyk2ERK1/2
2010
Acid regulation of NaDC-1 requires a functional endothelin B receptor
Liu L, Zacchia M, Tian X, Wan L, Sakamoto A, Yanagisawa M, Alpern RJ, Preisig PA. Acid regulation of NaDC-1 requires a functional endothelin B receptor. Kidney International 2010, 78: 895-904. PMID: 20703215, DOI: 10.1038/ki.2010.264.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAnimalsBiological TransportCell LineDicarboxylic Acid TransportersDisease Models, AnimalEndothelin B Receptor AntagonistsEndothelin-1Hydrogen-Ion ConcentrationKidneyMiceMice, KnockoutMicrovilliOligopeptidesOpossumsOrganic Anion Transporters, Sodium-DependentPiperidinesProtein Structure, TertiaryReceptor, Endothelin AReceptor, Endothelin BRecombinant Fusion ProteinsSignal TransductionSymportersTime FactorsTransfectionConceptsEndothelin-1Endothelin-B receptor antagonistFunctional endothelin B receptorsStimulatory effectAcid-stimulatory effectET-1 effectsB receptor antagonistNHE3 activityEndothelin B receptorWild-type miceET-1 stimulationMajor physiological stimulusNaDC-1Acid ingestionReceptor antagonistCitrate reabsorptionReceptor expressionCitrate excretionOpossum kidneyAcid loadB receptorAcid feedingPhysiological stimuliStimulationMice
2007
RhoA required for acid-induced stress fiber formation and trafficking and activation of NHE3
Yang X, Huang HC, Yin H, Alpern RJ, Preisig PA. RhoA required for acid-induced stress fiber formation and trafficking and activation of NHE3. American Journal Of Physiology. Renal Physiology 2007, 293: f1054-f1064. PMID: 17686951, DOI: 10.1152/ajprenal.00295.2007.Peer-Reviewed Original ResearchMeSH KeywordsAmidesAnimalsBenzoquinonesCell LineEnzyme InhibitorsExocytosisFocal Adhesion Kinase 1Hydrochloric AcidHydrogen-Ion ConcentrationLactams, MacrocyclicOpossumsPaxillinPhosphorylationProtein-Tyrosine KinasesPyridinesRhoA GTP-Binding ProteinRifabutinSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersStress FibersTyrosineConceptsStress fiber formationTyrosine phosphorylationFiber formationFocal adhesion proteinsApical membraneRho-kinaseNHE3 activityExocytic traffickingActivation of NHE3Exocytic processFocal adhesionsNHE3 exocytosisAdhesion proteinsStress fibersProtein abundancePaxillinPhosphorylationMicrofilament structureAntiporter activityKinaseRho-kinase inhibitorKinase inhibitorsTraffickingAbundanceNHE3 activation
2004
Pyk2 activation is integral to acid stimulation of sodium/hydrogen exchanger 3
Li S, Sato S, Yang X, Preisig PA, Alpern RJ. Pyk2 activation is integral to acid stimulation of sodium/hydrogen exchanger 3. Journal Of Clinical Investigation 2004, 114: 1782-1789. PMID: 15599403, PMCID: PMC535061, DOI: 10.1172/jci18046.Peer-Reviewed Original ResearchAcidsAdenosine TriphosphateADP-Ribosylation FactorsAnimalsCell LineCell-Free SystemFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesGenes, DominantGTPase-Activating ProteinsHydrogen-Ion ConcentrationImmunoblottingImmunoprecipitationKidney TubulesMutationOpossumsPhosphorylationProtein BindingProtein-Tyrosine KinasesRatsRats, Sprague-DawleyRNARNA, Small InterferingSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersTime FactorsTransfectionA consensus sequence in the endothelin-B receptor second intracellular loop is required for NHE3 activation by endothelin-1
Laghmani K, Sakamoto A, Yanagisawa M, Preisig PA, Alpern RJ. A consensus sequence in the endothelin-B receptor second intracellular loop is required for NHE3 activation by endothelin-1. American Journal Of Physiology. Renal Physiology 2004, 288: f732-f739. PMID: 15598844, DOI: 10.1152/ajprenal.00300.2004.Peer-Reviewed Original ResearchConceptsEndothelin-1Second intracellular loopET-1 stimulationNHE3 activityIntracellular loopEndothelin-A receptorAdenylyl cyclase inhibitionET-1 regulationProximal tubule apical membraneET receptorsCyclase inhibitionOKP cellsNHE3 activationOpossum kidneyExchanger 3ReceptorsStimulationProtein tyrosine phosphorylationReceptor chimerasPresent studyCellsAdditional mechanismTyrosine phosphorylationApical membraneSimilar patternAn autocrine role for endothelin-1 in the regulation of proximal tubule NHE3
Licht C, Laghmani K, Yanagisawa M, Preisig PA, Alpern RJ. An autocrine role for endothelin-1 in the regulation of proximal tubule NHE3. Kidney International 2004, 65: 1320-1326. PMID: 15086471, DOI: 10.1111/j.1523-1755.2004.00506.x.Peer-Reviewed Original ResearchConceptsChronic metabolic acidosisMetabolic acidosisReverse transcription-polymerase chain reactionProximal tubulesKidney cortexCompetitive reverse transcription-polymerase chain reactionProximal tubule NHE3NHE3 activityPreproET-1 expressionEndothelin B receptorEndothelin-1 expressionET-1 expressionPreproET-1 mRNA abundancePreproET-1 mRNA expressionTranscription-polymerase chain reactionProximal tubule cellsRenal proximal tubulesMRNA abundanceEndothelin-1Control ratsAbdominal aortaAutocrine roleAcidosisTubule cellsAutocrine regulationOKP cells express the Na-dicarboxylate cotransporter NaDC-1
Aruga S, Pajor AM, Nakamura K, Liu L, Moe OW, Preisig PA, Alpern RJ. OKP cells express the Na-dicarboxylate cotransporter NaDC-1. American Journal Of Physiology - Cell Physiology 2004, 287: c64-c72. PMID: 14973148, DOI: 10.1152/ajpcell.00061.2003.Peer-Reviewed Original ResearchConceptsCitrate reabsorptionOKP cellsProximal tubulesDependent citrate uptakeOpossum kidney cell lineUrinary citrate concentrationChronic metabolic acidosisRate of reabsorptionRenal proximal tubulesMetabolic acidosisStone formationKidney stonesKidney cell lineCotransporter 1ReabsorptionCell linesCitrate transportMRNA abundanceXenopus oocytesAcid regulationTubulesNaDC-1Citrate uptakeSuccinate transportHypocitraturiaDietary acid, endothelins, and sleep.
Alpern RJ, Preisig PA. Dietary acid, endothelins, and sleep. Transactions Of The American Clinical And Climatological Association 2004, 115: 385-93; discussion 393-4. PMID: 17060981, PMCID: PMC2263788.Peer-Reviewed Original ResearchConceptsTrafficking of NHE3Proximal tubule cell lineNHE3 activityTubule cell lineSecond intracellular loopEndothelin expressionDietary acidNHE3 abundanceActivation of NHE3OKP cellsProximal tubulesNHE3 mRNAApical membraneHomeostatic responseProtein expressionC-fosReceptor specificityIntracellular loopReceptorsEndothelinCell linesC-JunNHE3C-SrcAcid signaling
2002
Bicarbonate reabsorption and NHE-3 expression: Abundance and activity are increased in Henle's loop of remnant rats
Capasso G, Rizzo M, Pica A, Di Maio FS, Moe OW, Alpern RJ, De Santo NG. Bicarbonate reabsorption and NHE-3 expression: Abundance and activity are increased in Henle's loop of remnant rats. Kidney International 2002, 62: 2126-2135. PMID: 12427137, DOI: 10.1046/j.1523-1755.2002.00681.x.Peer-Reviewed Original ResearchRole of c-SRC and ERK in acid-induced activation of NHE3
Tsuganezawa H, Sato S, Yamaji Y, Preisig PA, Moe OW, Alpern RJ. Role of c-SRC and ERK in acid-induced activation of NHE3. Kidney International 2002, 62: 41-50. PMID: 12081562, DOI: 10.1046/j.1523-1755.2002.00418.x.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAmmonium ChlorideAnimalsCells, CulturedCSK Tyrosine-Protein KinaseEnzyme ActivationJNK Mitogen-Activated Protein KinasesMaleMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesPhosphorylationProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleySodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSrc-Family KinasesConceptsOKP cellsAcid-induced activationNHE3 activityERK/c-fosC-fos expressionC-Fos activationCytoplasmic pH (pHi) recoveryC-SrcRenal proximal tubulesAcid incubationActivation of NHE3Renal epithelial cellsCultured renal epithelial cellsProximal tubulesChronic acidosisInhibition of MEKNHE3 activationInhibited activationNormal levelsAcid loadImmune complex kinase assayERK kinaseAcidosisPH recoveryEpithelial cellsGlucagon Acutely Inhibits but Chronically Activates Na+/H+ Antiporter 3 Activity in OKP Cells
Amemiya M, Kusano E, Muto S, Tabei K, Ando Y, Alpern RJ, Asano Y. Glucagon Acutely Inhibits but Chronically Activates Na+/H+ Antiporter 3 Activity in OKP Cells. Experimental Nephrology 2002, 10: 26-33. PMID: 11803202, DOI: 10.1159/000049895.Peer-Reviewed Original ResearchConceptsNHE3 protein abundanceOKP cellsNHE3 activityCell pH recoveryRat renal proximal tubulesDibutyryl cAMPThick ascending limbRenal proximal tubulesWestern blot analysisM dibutyryl-cAMPChronic activationPKA-dependent pathwayProximal tubulesAscending limbGlucagonSurface membraneAcid loadNHE3 mRNAProtein abundancePH recoveryExchanger 3Independent mechanismsSignificant increaseBlot analysisP cellsThe role of endothelin in proximal tubule proton secretion and the adaptation to a chronic metabolic acidosis.
Laghmani K, Preisig PA, Alpern RJ. The role of endothelin in proximal tubule proton secretion and the adaptation to a chronic metabolic acidosis. Journal Of Nephrology 2002, 15 Suppl 5: s75-87. PMID: 12027224.Peer-Reviewed Original ResearchConceptsProximal tubulesMetabolic acidosisEndothelin-1NHE3 activityRole of endothelinImmediate early gene c-fosEndothelin B receptorEarly gene c-fosChronic metabolic acidosisGene c-fosKidney functionActivation of Pyk2Endothelin effectsApical membrane NHE3NHE3 abundanceB receptorEndothelinApical membraneAcidosisSecretionEffector agentsC-fosTubulesProton secretionC-Jun
2001
Endothelin-1/endothelin-B receptor–mediated increases in NHE3 activity in chronic metabolic acidosis
Laghmani K, Preisig P, Moe O, Yanagisawa M, Alpern R. Endothelin-1/endothelin-B receptor–mediated increases in NHE3 activity in chronic metabolic acidosis. Journal Of Clinical Investigation 2001, 107: 1563-1569. PMID: 11413164, PMCID: PMC200190, DOI: 10.1172/jci11234.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAmmoniaAnimalsBicarbonatesChronic DiseaseCitric AcidCulture TechniquesEndothelin-1EndothelinsKidney Tubules, ProximalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicProtein PrecursorsReceptor, Endothelin BReceptors, EndothelinRNA, MessengerSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsTg/tgAcid ingestionTitratable acid excretionMetabolic acidosisNHE3 activityAcid excretionReceptor-deficient miceEndothelin B receptorET-1 expressionChronic metabolic acidosisProximal tubule suspensionsAmmonium excretionM endothelinNa/H antiporterC57BL/6 miceApical membrane NHE3Renal epithelial cellsCultured renal epithelial cellsEndothelin-1/Tubule suspensionsMRNA expressionControl dietMiceExcretionEpithelial cellsETB receptor activation causes exocytic insertion of NHE3 in OKP cells
Peng Y, Amemiya M, Yang X, Fan L, Moe O, Yin H, Preisig P, Yanagisawa M, Alpern R. ETB receptor activation causes exocytic insertion of NHE3 in OKP cells. American Journal Of Physiology. Renal Physiology 2001, 280: f34-f42. PMID: 11133512, DOI: 10.1152/ajprenal.2001.280.1.f34.Peer-Reviewed Original ResearchConceptsEndothelin-1Sodium/hydrogen exchanger 3ET-1-induced increaseTotal cellular NHE3NHE3 activityNET traffickingTwo- to threefold increaseApical membrane NHE3OKP cellsMaximal effectReceptor activationClone PApical NHE3Exchanger 3NHE3Exocytic insertionThreefold increaseApical membraneCytochalasin D
2000
Acid incubation causes exocytic insertion of NHE3 in OKP cells
Yang X, Amemiya M, Peng Y, Moe O, Preisig P, Alpern R. Acid incubation causes exocytic insertion of NHE3 in OKP cells. American Journal Of Physiology - Cell Physiology 2000, 279: c410-c419. PMID: 10913008, DOI: 10.1152/ajpcell.2000.279.2.c410.Peer-Reviewed Original ResearchChronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat kidney
Aruga S, Wehrli S, Kaissling B, Moe O, Preisig P, Pajor A, Alpern R. Chronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat kidney. Kidney International 2000, 58: 206-215. PMID: 10886565, DOI: 10.1046/j.1523-1755.2000.00155.x.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAcidsAcute DiseaseAlkaliesAmmonium ChlorideAnimalsCarrier ProteinsChronic DiseaseCitratesDicarboxylic Acid TransportersGene ExpressionKidney CortexKidney Tubules, ProximalMaleMembrane ProteinsOrganic Anion Transporters, Sodium-DependentRatsRats, Sprague-DawleyRNA, MessengerSodium BicarbonateSymportersRenal citrate metabolism and urinary citrate excretion in the infant rat
Melnick J, Preisig P, Alpern R, Baum M. Renal citrate metabolism and urinary citrate excretion in the infant rat. Kidney International 2000, 57: 891-897. PMID: 10720942, PMCID: PMC4089854, DOI: 10.1046/j.1523-1755.2000.057003891.x.Peer-Reviewed Original ResearchConceptsUrinary citrate excretionHigher urinary citrateCitrate excretionInfant ratsAdult ratsUrinary citrateRenal citrate metabolismMitochondrial aconitase activityCreatinine ratioCitrate metabolismRenal excretionSame prevalenceRenal stonesTwofold higher concentrationLower plasmaATP citrate lyase activityProximal tubulesHigher plasmaMetabolic cagesRat kidneyRatsAdult levelsInfantsMaturational differencesExcretion
1999
Role of glucocorticoids in acidosis
Hamm L, Ambühl P, Alpern R. Role of glucocorticoids in acidosis. American Journal Of Kidney Diseases 1999, 34: 960-965. PMID: 10561158, DOI: 10.1016/s0272-6386(99)70059-4.Peer-Reviewed Original ResearchETB receptor activation leads to activation and phosphorylation of NHE3
Peng Y, Moe OW, Chu T, Preisig PA, Yanagisawa M, Alpern RJ. ETB receptor activation leads to activation and phosphorylation of NHE3. American Journal Of Physiology 1999, 276: c938-c945. PMID: 10199826, DOI: 10.1152/ajpcell.1999.276.4.c938.Peer-Reviewed Original ResearchIncubation of OKP cells in low-K+ media increases NHE3 activity after early decrease in intracellular pH
Amemiya M, Tabei K, Kusano E, Asano Y, Alpern R. Incubation of OKP cells in low-K+ media increases NHE3 activity after early decrease in intracellular pH. American Journal Of Physiology 1999, 276: c711-c716. PMID: 10069999, DOI: 10.1152/ajpcell.1999.276.3.c711.Peer-Reviewed Original ResearchConceptsOKP cellsEarly decreaseNHE3 activityNHE3 protein abundanceTyrosine kinase inhibitorsProximal tubule apical membraneChronic hypokalemiaTyrosine kinase pathwayIntracellular acidosisNHE3 mRNAKinase inhibitorsControl levelsNHE3Herbimycin AKinase pathwayControl mediumPresent studySodium propionateIntracellularCellsAntiporter activityApical membraneHypokalemiaIncubationProtein abundance