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
2007
The acid-activated signaling pathway: Starting with Pyk2 and ending with increased NHE3 activity
Preisig PA. The acid-activated signaling pathway: Starting with Pyk2 and ending with increased NHE3 activity. Kidney International 2007, 72: 1324-1329. PMID: 17882150, DOI: 10.1038/sj.ki.5002543.Peer-Reviewed Original ResearchConceptsTypical Western dietSystemic acid-base balanceMultiple nephron segmentsProximal tubule cellsAcid-base balanceNa/H antiporterWestern dietBicarbonate reclamationProximal tubulesTubule cellsNephron segmentsAcid loadAmmonium secretionLuminal protonsNHE3 activityH antiporterSecretionNHE3Titratable acid
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
Compensatory renal hypertrophy is mediated by a cell cycle-dependent mechanism
Liu B, Preisig PA. Compensatory renal hypertrophy is mediated by a cell cycle-dependent mechanism. Kidney International 2002, 62: 1650-1658. PMID: 12371965, DOI: 10.1046/j.1523-1755.2002.00620.x.Peer-Reviewed Original ResearchConceptsCdk2/cyclin E kinase activityCyclin E kinase activityTubule hypertrophyDay 4BrdU incorporationDevelopment of hypertrophyCyclin D kinaseCompensatory renal hypertrophyCell cycle-dependent mechanismProximal tubule proteinsTubule growthHypertrophic formUninephrectomized animalsNephrectomized ratsRenal hypertrophyC57BL6 miceRenal cortexKinase activityDay 2Proximal tubulesHypertrophyHypertrophy markersRatsKinase inhibitorsMiceThe 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 ExchangersG1 kinases and transforming growth factor-β; signaling are associated with a growth pattern switch in diabetes-induced renal growth
Huang H, Preisig P. G1 kinases and transforming growth factor-β; signaling are associated with a growth pattern switch in diabetes-induced renal growth. Kidney International 2000, 58: 162-172. PMID: 10886561, DOI: 10.1046/j.1523-1755.2000.00151.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCDC2-CDC28 KinasesCyclin ECyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Cyclin-Dependent KinasesDiabetes Mellitus, ExperimentalDiabetic NephropathiesDNA-Binding ProteinsG1 PhaseHyperplasiaHypertrophyKidney Tubules, ProximalMaleProtein Serine-Threonine KinasesProto-Oncogene ProteinsRatsRats, Sprague-DawleyReceptors, Transforming Growth Factor betaSignal TransductionSmad2 ProteinSmad4 ProteinTrans-ActivatorsTransforming Growth Factor betaConceptsReceptor II expressionCyclin E kinase activityReceptor expressionRenal growthGrowth factor beta receptor expressionTGF-beta receptor II expressionBaseline levelsProximal tubule cell growthTGF-beta receptor expressionBody weight ratioCdk2/cyclin E kinase activityCdk2/cyclin E complexesCyclin DRenal proximal tubulesDiabetes mellitusDiabetic ratsTGF-beta signalingDiabetic stateCyclin E complexGrowth patternDay 2Proximal tubulesDay 4Day 10Tubule growthChronic 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
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 Research
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 progression
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-ATPaseTubules
1992
Luminal flow rate regulates proximal tubule H-HCO3 transporters
Preisig P. Luminal flow rate regulates proximal tubule H-HCO3 transporters. American Journal Of Physiology 1992, 262: f47-f54. PMID: 1310229, DOI: 10.1152/ajprenal.1992.262.1.f47.Peer-Reviewed Original ResearchConceptsLuminal flow rateLuminal perfusateNa-H antiporter activityProximal tubule acidificationProgressive increaseRate-dependent changesNa-H antiporterTubule acidificationVivo microperfusionH secretionLuminal amilorideAcid loadSecretory activityAlkali loadPerfusateSensitive indexSymporter activityDisulfonic acidAntiporter activityMinBase transportActivityMicroperfusionInitial rateSecretion
1991
Chronic adaptations in proximal tubular H/HCO3 transporters.
Alpern RJ, Horie S, Moe O, Tejedor A, Miller RT, Preisig PA. Chronic adaptations in proximal tubular H/HCO3 transporters. Kidney International Supplement 1991, 33: s29-32. PMID: 1653870.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsBicarbonatesCarrier ProteinsExtracellular SpaceIntracellular MembranesKidney Tubules, ProximalSignal TransductionSodium-Hydrogen ExchangersConceptsCultured proximal tubule cellsChronic hyperfiltrationNa/H antiporterProximal tubule cellsChronic acidosisTubule cellsNa/H antiporter activityH antiporterK deficiencyEffect of acidosisExtracellular fluid pHChronic adaptationsAcidosisHyperfiltrationCotransporter activityAbundance of mRNAParallel increaseHCO3- transportersAcid preincubationDeficiencyFluid pHCellsAntiporter activityProtein synthesisExtracellular signalsRegulation of proximal reabsorption by effective arterial blood volume.
Seldin DW, Preisig PA, Alpern RJ. Regulation of proximal reabsorption by effective arterial blood volume. Seminars In Nephrology 1991, 11: 212-9. PMID: 2034926.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBicarbonatesBiological TransportBlood VolumeHumansKidney Concentrating AbilityKidney Tubules, ProximalRenal CirculationSodiumSodium ChlorideWater-Electrolyte BalanceConceptsEffective arterial blood volumeEffective arterial volumeRenal nerve activityProximal tubular transportAtrial natriuretic factorArterial blood volumeLevels of hormonesRenal hemodynamicsNerve activityDietary NaClAngiotensin IIProximal reabsorptionNatriuretic factorBlood volumeTubular transportProximal tubulesChronic effectsArterial volumeOncotic pressureNorepinephrineHemodynamicsEpinephrineHormoneReabsorptionIncreased Na/H antiporter and Na/3HCO3 symporter activities in chronic hyperfiltration. A model of cell hypertrophy.
Preisig PA, Alpern RJ. Increased Na/H antiporter and Na/3HCO3 symporter activities in chronic hyperfiltration. A model of cell hypertrophy. The Journal Of General Physiology 1991, 97: 195-217. PMID: 1849958, PMCID: PMC2216475, DOI: 10.1085/jgp.97.2.195.Peer-Reviewed Original ResearchConceptsHyperfiltration groupChronic hyperfiltrationNa/H antiporterKidney weightCell hypertrophyHigher glomerular filtration rateNa/H antiporter activityH antiporterGlomerular filtration rateVivo microperfused rat proximal tubuleCell pHRat proximal tubuleSymporter activityFiltration rateProximal tubulesUltrafiltrate-like solutionHyperfiltrationSteady-state cell pHProtein feedingPeritubular perfusateDietary proteinParallel increaseUninephrectomyHypertrophyCell acidification
1990
Cellular model of proximal tubule NaCl and NaHCO3 absorption
Moe O, Preisig P, Alpern R. Cellular model of proximal tubule NaCl and NaHCO3 absorption. Kidney International 1990, 38: 605-611. PMID: 2172616, DOI: 10.1038/ki.1990.249.Peer-Reviewed Original ResearchPathways for apical and basolateral membrane NH3 and NH4+ movement in rat proximal tubule
Preisig PA, Alpern RJ. Pathways for apical and basolateral membrane NH3 and NH4+ movement in rat proximal tubule. American Journal Of Physiology 1990, 259: f587-f593. PMID: 2221097, DOI: 10.1152/ajprenal.1990.259.4.f587.Peer-Reviewed Original ResearchMeSH KeywordsAmilorideAmmoniaAnimalsBiological TransportBuffersCell Membrane PermeabilityKidney Tubules, ProximalOsmolar ConcentrationQuaternary Ammonium CompoundsRats
1989
Contributions of cellular leak pathways to net NaHCO3 and NaCl absorption.
Preisig PA, Alpern RJ. Contributions of cellular leak pathways to net NaHCO3 and NaCl absorption. Journal Of Clinical Investigation 1989, 83: 1859-1867. PMID: 2542374, PMCID: PMC303906, DOI: 10.1172/jci114092.Peer-Reviewed Original Research