2009
Biochemical and histological assessment of Alkali therapy during high animal protein intake in the rat
Zerwekh JE, Zou L, Pak CY, Moe OW, Preisig PA. Biochemical and histological assessment of Alkali therapy during high animal protein intake in the rat. Bone 2009, 45: 1004-1009. PMID: 19651255, PMCID: PMC2753741, DOI: 10.1016/j.bone.2009.07.077.Peer-Reviewed Original ResearchConceptsHigh animal protein intakeAnimal protein intakeAlkali therapyBone histomorphometryBone turnoverProtein intakeAcid loadChronic acid loadMajor skeletal effectCancellous bone volumeHigh casein dietNegative calcium balanceDynamic bone histomorphometryLow urinary pHBone formation rateDietary animal protein intakeStatic bone histomorphometryNet acid excretionLow caseinSubstantial acid loadOsteoclastic surfaceWesternized dietUrinary pHUrine biochemistryBone resorption
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
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 FactorsTransfectionAn 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
2003
Effect of high protein diet on stone-forming propensity and bone loss in rats
Amanzadeh J, Gitomer WL, Zerwekh JE, Preisig PA, Moe OW, Pak CY, Levi M. Effect of high protein diet on stone-forming propensity and bone loss in rats. Kidney International 2003, 64: 2142-2149. PMID: 14633136, DOI: 10.1046/j.1523-1755.2003.00309.x.Peer-Reviewed Original ResearchConceptsHigh casein dietHigh casein groupBone lossCasein groupCasein dietHigh-protein dietProtein dietPathogenesis of hypercalciuriaSerum calcitriol concentrationsStone-forming propensityUrinary calcium excretionBrush border membraneRisk of nephrolithiasisUrinary citrate excretionHigh protein intakeLow casein dietHigher urinary volumeResponse of kidneyNet acid excretionSubstantial acid loadKidney stone formationDays of studyCalcium excretionCalcitriol concentrationsCortical brush border membrane
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 inhibitorsMiceRole 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 cells
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 BicarbonateSymportersG1 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 growthRenal 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
TGF-β1-mediated hypertrophy involves inhibiting pRB phosphorylation by blocking activation of cyclin E kinase
Liu B, Preisig P. TGF-β1-mediated hypertrophy involves inhibiting pRB phosphorylation by blocking activation of cyclin E kinase. American Journal Of Physiology 1999, 277: f186-f194. PMID: 10444572, DOI: 10.1152/ajprenal.1999.277.2.f186.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCdc25 PhosphatasesCDC2-CDC28 KinasesCell Cycle ProteinsCell LineCyclin ECyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Cyclin-Dependent Kinase Inhibitor p27Cyclin-Dependent Kinase Inhibitor p57Cyclin-Dependent KinasesEnzyme ActivationEpidermal Growth FactorHypertrophyKidneyMicrotubule-Associated ProteinsNuclear ProteinsPhosphorylationProtein Serine-Threonine KinasesProtein Tyrosine PhosphatasesProto-Oncogene ProteinsRatsRetinoblastoma ProteinTransforming Growth Factor betaTumor Suppressor ProteinsConceptsCdk2/cyclin E complexesCyclin E complexCyclin E kinaseGrowth responseE complexCell cycle progressionRenal epithelial cellsProtein abundanceRetinoblastoma proteinKinase activityCycle progressionHypophosphorylated statePRB phosphorylationHypertrophic growth responseKinaseCyclin EAbundanceEpithelial cellsActive stateDevelopment of hypertrophyActivationCell entranceComplexesArrestTGF-β1
1998
Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia
Melnick J, Preisig P, Haynes S, Pak C, Sakhaee K, Alpern R. Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia. Kidney International 1998, 54: 1670-1674. PMID: 9844143, DOI: 10.1046/j.1523-1755.1998.00150.x.Peer-Reviewed Original ResearchConceptsUrinary citrate excretionCitrate excretionUrinary citrateMetabolic acidosisATP-citrate lyaseEffects of enalaprilRenal citrate metabolismUrine citrate concentrationRenal cortical tissueChronic metabolic acidosisProximal tubular cellsPlasma pHNa/H antiporterAngiotensin IIIntracellular acidosisEnalaprilTubular cellsCitrate lyaseHypokalemiaEnzyme inhibitorsATP citrate lyase activityAcidosisCortical tissueRatsCitrate metabolismRenal 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
1996
Adenosine triphosphate citrate lyase mediates hypocitraturia in rats.
Melnick JZ, Srere PA, Elshourbagy NA, Moe OW, Preisig PA, Alpern RJ. Adenosine triphosphate citrate lyase mediates hypocitraturia in rats. Journal Of Clinical Investigation 1996, 98: 2381-2387. PMID: 8941657, PMCID: PMC507690, DOI: 10.1172/jci119051.Peer-Reviewed Original ResearchConceptsChronic metabolic acidosisMetabolic acidosisATP citrate lyase activityATP-citrate lyaseCitrate lyase activityCitrate lyaseHypocitraturiaAcid dietAcidosisCitrate metabolismProtein abundanceRatsMRNA abundanceLyase activityMetabolismPresent studySignificant changesCitrate uptakeInhibitionHypercitraturiaHypokalemiaCytosolic enzymeCompetitive inhibitorActivityImportant roleChronic 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 studyLimbTubulesNH4Cl-induced hypertrophy is mediated by weak base effects and is independent of cell cycle processes
Franch H, Preisig P. NH4Cl-induced hypertrophy is mediated by weak base effects and is independent of cell cycle processes. American Journal Of Physiology 1996, 270: c932-c938. PMID: 8638677, DOI: 10.1152/ajpcell.1996.270.3.c932.Peer-Reviewed Original ResearchConceptsC-fos mRNA abundanceHuman papilloma virus 16NRK-52E cellsWeak base propertiesCell cycle processRenal hypertrophyClinical conditionsVirus 16Renal epithelial cellsCultured renal epithelial cellsCell cycleHypertrophyE7 genesAdditional studiesEpithelial cellsVesicular alkalinizationMRNA abundancePresent studyInactivation of pRbCellsProtein synthesisVacuolar proton pumpProtein abundanceVesicular compartments
1995
Involvement 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
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 K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter
Levi M, McDonald LA, Preisig PA, Alpern RJ. Chronic K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter. American Journal Of Physiology 1991, 261: f767-f773. PMID: 1683169, DOI: 10.1152/ajprenal.1991.261.5.f767.Peer-Reviewed Original Research