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 regulationDietary 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. Nephron 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 cells
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 ResearchMeSH KeywordsAcidosis, Renal TubularAnimalsCytoplasmHydrogen-Ion ConcentrationIonophoresKidney Tubules, ProximalNigericinOpossumsSodium-Hydrogen Exchanger 3Sodium-Hydrogen Exchangers
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 abundanceGlucocorticoids enhance acid activation of the Na+/H+ exchanger 3 (NHE3)
Ambühl P, Yang X, Peng Y, Preisig P, Moe O, Alpern R. Glucocorticoids enhance acid activation of the Na+/H+ exchanger 3 (NHE3). Journal Of Clinical Investigation 1999, 103: 429-435. PMID: 9927505, PMCID: PMC407891, DOI: 10.1172/jci2913.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportCell LineGlucocorticoidsHydrogen-Ion ConcentrationSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsNHE3 protein abundanceM hydrocortisoneNHE3 activityAcid incubationNHE3 mRNA abundanceTrafficking of NHE3Absence of hydrocortisoneOpossum kidney cellsExogenous glucocorticoidsExchanger 3 (NHE3) activityHydrocortisoneProtein abundanceGlucocorticoidsProtein synthesisExchanger 3Kidney cellsTwofold increaseMRNA abundanceApical membrane
1998
Renal Na/H exchanger NHE-3 and Na-PO4 cotransporter NaPi-2 protein expression in glucocorticoid excess and deficient states.
Loffing J, Lötscher M, Kaissling B, Biber J, Murer H, Seikaly M, Alpern RJ, Levi M, Baum M, Moe OW. Renal Na/H exchanger NHE-3 and Na-PO4 cotransporter NaPi-2 protein expression in glucocorticoid excess and deficient states. Journal Of The American Society Of Nephrology 1998, 9: 1560-7. PMID: 9727362, PMCID: PMC4131923, DOI: 10.1681/asn.v991560.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 3Adaptor Protein Complex beta SubunitsAdrenalectomyAnalysis of VarianceAnimalsBiological Transport, ActiveCarrier ProteinsDisease Models, AnimalGlucocorticoidsImmunoblottingImmunohistochemistryKidney CortexMaleNerve Tissue ProteinsPhosphoproteinsRatsRats, Sprague-DawleySensitivity and SpecificitySodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSodium-Phosphate Cotransporter ProteinsSymportersConceptsNa/H exchangeNHE-3 protein abundanceNHE-3Glucocorticoid excessPharmacologic dosesNaPi-2 proteinProximal tubulesSham-operated ratsNaPi-2Sham-operated animalsThick ascending limbSignificant reciprocal increaseBilateral adrenalectomyDexamethasone administrationIntrarenal distributionControl ratsProtein abundanceAscending limbReciprocal increaseAdrenalectomyRatsDeficient stateCotransport activityProtein expressionAdministrationDominant negative c-Src inhibits angiotensin II induced activation of NHE3 in OKP cells
Tsuganezawa H, Preisig P, Alpern R. Dominant negative c-Src inhibits angiotensin II induced activation of NHE3 in OKP cells. Kidney International 1998, 54: 394-398. PMID: 9690205, DOI: 10.1046/j.1523-1755.1998.00029.x.Peer-Reviewed Original ResearchConceptsNa/H antiporter activityAngiotensin IIOKP cellsInhibits angiotensin IIVascular smooth muscleTyrosine kinase inhibitorsC-SrcHerbimycin AAntiporter activityNa/H antiporterActivation of NHE3Smooth muscleProximal tubulesPotent stimulatorNHE3 activationRegulation of NHE3Key mediatorKinase inhibitorsClonal cell linesNHE3 activityAntiporter activationCyclic AMPCell linesNHE3AcidosisEffects of thyroid hormone on the neonatal renal cortical Na+/H+ antiporter
Baum M, Dwarakanath V, Alpern R, Moe O. Effects of thyroid hormone on the neonatal renal cortical Na+/H+ antiporter. Kidney International 1998, 53: 1254-1258. PMID: 9573540, PMCID: PMC4131927, DOI: 10.1046/j.1523-1755.1998.00879.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAntithyroid AgentsFemaleHyperthyroidismHypothyroidismKidney CortexKidney Tubules, ProximalMaternal-Fetal ExchangePregnancyPropylthiouracilRatsRats, Sprague-DawleyRNA, MessengerSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSodium-Potassium-Exchanging ATPaseTriiodothyronineConceptsThyroid hormonesHyperthyroid neonatesNHE-3 protein abundanceNHE-3 mRNA abundanceDays of lifeLower ratesNeonatal proximal tubuleAntiporter activityHypothyroid neonatesHyperthyroid groupMaturational increaseProximal tubulesPostnatal increaseHyperthyroid ratsBicarbonate absorptionPmol/NeonatesHormonePotential roleBrush borderEuthyroidOne-thirdRatsMRNA abundanceApical membraneChronic hyperosmolality increases NHE3 activity in OKP cells.
Ambühl P, Amemiya M, Preisig PA, Moe OW, Alpern RJ. Chronic hyperosmolality increases NHE3 activity in OKP cells. Journal Of Clinical Investigation 1998, 101: 170-177. PMID: 9421479, PMCID: PMC508553, DOI: 10.1172/jci62.Peer-Reviewed Original ResearchMeSH KeywordsAmilorideAnimalsCell LineCulture MediaGlucoseHypertonic SolutionsKidneyMannitolOpossumsOsmolar ConcentrationRaffinoseSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersUreaConceptsNa/H exchanger 3Na/H antiporter activityDiabetes mellitusNHE3 mRNA abundanceNHE3 protein abundanceAntiporter activityChronic hypertonicityGlomerular hyperfiltrationDiabetic nephropathyNa/H antiporterChronic hyperosmolalityOKP cellsExchanger 3MOsm/NHE3 activityRelevant increaseMellitusSignificant increaseChronicH antiporterExtracellular glucoseHypertonic incubationMRNA abundanceHypertonicitySmall increase
1997
Chronic metabolic acidosis enhances NHE-3 protein abundance and transport activity in the rat thick ascending limb by increasing NHE-3 mRNA.
Laghmani K, Borensztein P, Ambühl P, Froissart M, Bichara M, Moe OW, Alpern RJ, Paillard M. Chronic metabolic acidosis enhances NHE-3 protein abundance and transport activity in the rat thick ascending limb by increasing NHE-3 mRNA. Journal Of Clinical Investigation 1997, 99: 24-30. PMID: 9011571, PMCID: PMC507763, DOI: 10.1172/jci119128.Peer-Reviewed Original Research