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 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
The 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 ResearchMeSH KeywordsAcidosisAdaptation, PhysiologicalAnimalsChronic DiseaseEndothelinsKidney Tubules, ProximalProtonsConceptsProximal 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 cells
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 ExchangersChronic 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 BicarbonateSymporters
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 Research
1998
Renal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia
Melnick J, Preisig P, Moe O, Srere P, Alpern R. Renal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia. Kidney International 1998, 54: 160-165. PMID: 9648074, DOI: 10.1046/j.1523-1755.1998.00974.x.Peer-Reviewed Original ResearchEffects 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
1997
Media acidification inhibits TGF beta-mediated growth suppression in cultured rabbit proximal tubule cells.
Tovbin D, Franch HA, Alpern RJ, Preisig PA. Media acidification inhibits TGF beta-mediated growth suppression in cultured rabbit proximal tubule cells. Proceedings Of The Association Of American Physicians 1997, 109: 572-9. PMID: 9394419.Peer-Reviewed Original ResearchConceptsDirect antiproliferative effectRabbit proximal tubule cellsProximal tubule cellsAntiproliferative effectsGrowth-suppressive effectsMetabolic acidosisCultured rabbit proximal tubule cellsTubule cellsChronic metabolic acidosisInhibits cell cycle progressionRenal functionRenal growthMitogen-stimulated cellsRenal epithelial cellsProgressive lossHyperplasiaHypertrophyCell cycle progressionEpithelial cellsPrimary culturesPRB phosphorylationAcidosisEGF-induced phosphorylationGrowth suppressionCycle progressionIntracellular acidosis activates c-Src
Yamaji Y, Tsuganezawa H, Moe OW, Alpern RJ. Intracellular acidosis activates c-Src. American Journal Of Physiology 1997, 272: c886-c893. PMID: 9124524, DOI: 10.1152/ajpcell.1997.272.3.c886.Peer-Reviewed Original ResearchMeSH KeywordsAcidosisAnimalsCell LineCytosolEnzyme ActivationKidney Tubules, ProximalMicePhosphotyrosinePropionatesProto-Oncogene Proteins pp60(c-src)VanadatesConceptsC-SrcC-Src activationProtein tyrosine phosphatase inhibitorProtein tyrosine kinase pathwaysMedium acidificationTyrosine phosphatase inhibitorProtein tyrosine phosphorylationC-Src activityTyrosine kinase pathwayPhosphatase inhibitorPhosphotyrosine contentCell pH changesTyrosine phosphorylationCytosolic proteinsKinase pathwayRenal proximal tubule cell lineCellular responsesSodium orthovanadateNovel mechanismProximal tubule cell lineCell linesTubule cell lineCell acidificationSignificant activationActivation
1996
Glucocorticoids 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 ResearchMeSH KeywordsAnimalsCell LineDexamethasoneDrug StabilityKidney Tubules, ProximalOpossumsRNA, MessengerSodium-Hydrogen ExchangersTime FactorsTranscription, GeneticConceptsNHE-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 ResearchMeSH KeywordsAnimalsBicarbonatesGene ExpressionGenes, srcHumansKidney Tubules, ProximalSignal TransductionSodium-Hydrogen ExchangersTime FactorsConceptsNa/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 absorption
1994
Acid activation of immediate early genes in renal epithelial cells.
Yamaji Y, Moe OW, Miller RT, Alpern RJ. Acid activation of immediate early genes in renal epithelial cells. Journal Of Clinical Investigation 1994, 94: 1297-1303. PMID: 8083371, PMCID: PMC295215, DOI: 10.1172/jci117448.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAcidosisAnimalsCell LineCell NucleusDNA-Binding ProteinsEarly Growth Response Protein 1EpitheliumGene Expression RegulationGenes, Immediate-EarlyHydrogen-Ion ConcentrationImmediate-Early ProteinsIonomycinKidney Tubules, ProximalMiceProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junRNA, MessengerTetradecanoylphorbol AcetateTranscription FactorsTranscriptional ActivationConceptsTyrosine kinase pathwayGene activationKinase pathwayMouse proximal tubule cell lineC-JunRate of transcriptionProtein kinase CImmediate early genesRenal epithelial cellsMRNA speciesPretreatment of cellsGene expressionKinase CEarly genesGenesMRNA abundanceProximal tubule cell lineCell linesTubule cell lineRenal tubule cellsEpithelial cellsC-fosGrowth factorCellsMRNAEffect 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 vesiclesAdministration
1993
The renal proximal tubule renin-angiotensin system.
Moe O, Alpern R, Henrich W. The renal proximal tubule renin-angiotensin system. Seminars In Nephrology 1993, 13: 552-7. PMID: 8278688.Peer-Reviewed Original ResearchConceptsProximal tubule renin-angiotensin systemProximal tubulesRenin-angiotensin systemAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseasePolycystic kidney diseaseEssential hypertensionKidney diseasePathogenetic roleRenal vasculatureJG cellsCyst growthMammalian proximal tubuleHypertensionReninTubulesComplete RASPatientsDiseaseAutocrineParacrineRAVasculatureRenin expression in renal proximal tubule.
Moe OW, Ujiie K, Star RA, Miller RT, Widell J, Alpern RJ, Henrich WL. Renin expression in renal proximal tubule. Journal Of Clinical Investigation 1993, 91: 774-779. PMID: 7680667, PMCID: PMC288027, DOI: 10.1172/jci116296.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBlotting, SouthernCells, CulturedCloning, MolecularColforsinEnalaprilIn Vitro TechniquesIsoproterenolKidney Tubules, ProximalKineticsMaleMolecular Sequence DataMuscle, Smooth, VascularOligodeoxyribonucleotidesPoly APolymerase Chain ReactionRabbitsRatsRats, Sprague-DawleyReninRNARNA, MessengerTranscription, GeneticConceptsProximal tubule cellsCultured proximal tubule cellsRenin-angiotensin systemProximal tubulesRenal proximal tubulesTubule cellsRenin activityLocal renin-angiotensin systemPrimary culturesPresence of reninRabbit proximal tubule cellsAngiotensin-converting enzymeMammalian renal proximal tubulePrevious immunohistochemical studiesSynthesized reninAngiotensin receptorsAngiotensin IIRenin contentPolymerase chain reactionRenin expressionImmunohistochemical studyM isoproterenolM forskolinNormal ratsRenin mRNACell pH and transepithelial H/HCO3 transport in the renal proximal tubule
Krapf R, Alpern R. Cell pH and transepithelial H/HCO3 transport in the renal proximal tubule. The Journal Of Membrane Biology 1993, 131: 1-10. PMID: 8381871, DOI: 10.1007/bf02258529.Peer-Reviewed Original Research