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
2004
An 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
Role 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
2000
Chronic 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
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 membrane
1996
Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney
Ambuhl P, Amemiya M, Danczkay M, Lotscher M, Kaissling B, Moe OW, Preisig PA, Alpern RJ. Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney. American Journal Of Physiology 1996, 271: f917-f925. PMID: 8898023, DOI: 10.1152/ajprenal.1996.271.4.f917.Peer-Reviewed Original ResearchConceptsNHE3 protein abundanceChronic metabolic acidosisNHE3 mRNA abundanceMetabolic acidosisThick ascending limbProximal tubulesAscending limbNa/H antiporter activityAcidosis-induced increaseMRNA abundanceNa/H antiporterNHE3 abundanceProtein abundanceAcidosisRat kidneyWestern blotS2 segmentsH antiporterRatsNHE3 isoformPresent studyLimbTubulesGlucocorticoids regulate NHE-3 transcription in OKP cells
Baum M, Amemiya M, Dwarakanath V, Alpern RJ, Moe OW. Glucocorticoids regulate NHE-3 transcription in OKP cells. American Journal Of Physiology 1996, 270: f164-f169. PMID: 8769835, DOI: 10.1152/ajprenal.1996.270.1.f164.Peer-Reviewed Original ResearchConceptsNHE-3 mRNA abundanceGlucocorticoid-mediated increaseOKP cellsDexamethasone-treated cellsNHE-3 mRNAMRNA abundanceTwo- to threefold increaseAntiporter activitySynthetic glucocorticoidProximal tubulesApical proton secretionM dexamethasoneDexamethasoneNHE-3GlucocorticoidsTime courseProton secretionThreefold increasePresent studyCellsGene transcriptionMRNASecretionActivity
1995
Chronic regulation of the proximal tubular Na/H antiporter: From HCO3 to SRC
Alpern R, Moe O, Preisig P. Chronic regulation of the proximal tubular Na/H antiporter: From HCO3 to SRC. Kidney International 1995, 48: 1386-1396. PMID: 8544394, DOI: 10.1038/ki.1995.427.Peer-Reviewed Original ResearchConceptsNa/H antiporterChronic regulationH secretionProximal tubulesH antiporterNaCl absorptionProximal tubular acidificationMajor siteNa/K pumpCitrate reabsorptionBasolateral membraneTubular acidificationAcute regulationLuminal membraneK pumpExcretionReabsorptionSecretionPivotal roleVacuolar H-ATPaseH-ATPaseTubulesExpression of NHE-3 in the apical membrane of rat renal proximal tubule and thick ascending limb
Amemiya M, Loffing J, Lötscher M, Kaissling B, Alpern R, Moe O. Expression of NHE-3 in the apical membrane of rat renal proximal tubule and thick ascending limb. Kidney International 1995, 48: 1206-1215. PMID: 8569082, DOI: 10.1038/ki.1995.404.Peer-Reviewed Original ResearchConceptsThick ascending limbAscending limbNHE-3H secretionNa/H exchanger isoformsProximal tubulesCortical thick ascending limbNa/H exchange activityS3 proximal tubuleDistal convoluted tubuleRat renal proximal tubulesNa/H exchangeH exchange activityRenal proximal tubulesRat NHE-3Apical membraneAbsent stainingMock-transfected cellsCortical membranesConvoluted tubulesInner stripeStrong stainingWeak stainingOuter medullaNa absorptionRenal Proximal Tubule Response to Acid
Alpern R, Yamaji Y, Amemiya M, Cano A, Preisig P, Miller, Moe O. Renal Proximal Tubule Response to Acid. Physiology 1995, 10: 77-81. DOI: 10.1152/physiologyonline.1995.10.2.77.Peer-Reviewed Original ResearchInvolvement of pRB family in TGF beta-dependent epithelial cell hypertrophy.
Franch HA, Shay JW, Alpern RJ, Preisig PA. Involvement of pRB family in TGF beta-dependent epithelial cell hypertrophy. Journal Of Cell Biology 1995, 129: 245-254. PMID: 7698989, PMCID: PMC2120382, DOI: 10.1083/jcb.129.1.245.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Polyomavirus TransformingBlotting, NorthernCell CycleCell DivisionCell LineCells, CulturedEpidermal Growth FactorEpithelial CellsEpitheliumGene ExpressionHumansHypertrophyKidneyKidney TubulesKineticsOncogene Proteins, ViralPapillomavirus E7 ProteinsPhosphorylationProto-Oncogene Proteins c-fosRabbitsRatsRecombinant ProteinsRepressor ProteinsRetinoblastoma ProteinRNA, MessengerTransfectionTransforming Growth Factor betaTumor Suppressor Protein p53ConceptsEpithelial cell hypertrophyNRK-52E cellsCell hypertrophyHPV16 E6TGF betaSV40 large T antigenC-fos mRNA abundanceGrowth factor beta 1SV40 large T antigen expressionLarge T antigenLarge T antigen expressionMechanisms of hypertrophyRenal cell hypertrophyRabbit proximal tubuleActive pRbT-antigen expressionRenal functionT antigenRenal hypertrophyAntigen expressionEpidermal growth factorEGF-induced increaseProximal tubulesHypertrophyHPV16 E7
1994
Effect of glucocorticoids on renal cortical NHE-3 and NHE-1 mRNA
Baum M, Moe OW, Gentry DL, Alpern RJ. Effect of glucocorticoids on renal cortical NHE-3 and NHE-1 mRNA. American Journal Of Physiology 1994, 267: f437-f442. PMID: 8092257, DOI: 10.1152/ajprenal.1994.267.3.f437.Peer-Reviewed Original ResearchConceptsNHE-3 mRNA abundanceProximal tubulesNHE-3NHE-1MRNA abundanceChronic systemic administrationAdministration of dexamethasoneEffects of glucocorticoidsProximal tubule acidificationNHE-1 mRNAUnits/minChronic dexamethasoneTubule acidificationAcute increaseAntiporter activitySystemic administrationGlucocorticoid deficiencyIntravenous administrationBicarbonate absorptionMicrograms/DexamethasoneAntiporter isoformsDexamethasone occursRenal brush-border membrane vesiclesAdministrationAngiotensin II stimulation of Na-H antiporter activity is cAMP independent in OKP cells
Cano A, Miller RT, Alpern RJ, Preisig PA. Angiotensin II stimulation of Na-H antiporter activity is cAMP independent in OKP cells. American Journal Of Physiology 1994, 266: c1603-c1608. PMID: 8023891, DOI: 10.1152/ajpcell.1994.266.6.c1603.Peer-Reviewed Original ResearchConceptsPertussis toxin-sensitive G proteinToxin-sensitive G proteinNa-H antiporter activityAngiotensin IINa-H antiporterOKP cellsAngiotensin II concentrationAngiotensin II receptorsAbsence of IBMXAngiotensin II stimulationG proteinsCyclic monophosphateProximal tubule apical membraneOpossum kidney cellsConcentration-dependent mannerCAMP-independent mechanismM losartanAcute treatmentAT1 receptorII stimulationPertussis toxinII receptorsProximal tubulesCAMP productionStimulatory effect