Fructose Acutely Stimulates NHE3 Activity in Kidney Proximal Tubule

dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorQUEIROZ-LEITE, Gabriella D.
dc.contributor.authorCRAJOINAS, Renato O.
dc.contributor.authorNERI, Elida A.
dc.contributor.authorBEZERRA, Camila N. A.
dc.contributor.authorGIRARDI, Adriana C. C.
dc.contributor.authorREBOUCAS, Nancy Amaral
dc.contributor.authorMALNIC, Gerhard
dc.date.accessioned2013-10-02T19:43:00Z
dc.date.available2013-10-02T19:43:00Z
dc.date.issued2012
dc.description.abstractBackground/Aims: Fructose causes a sodium-sensitive hypertension and acutely reduces the urinary Na+ excretion, suggesting that it may regulate the activity of renal tubular sodium transporters. NHE3 is highly expressed in proximal tubule (PT), along with proteins that mediate fructose transport and metabolism. The present work was outlined to investigate whether fructose modulates proximal NHE3 activity and to elucidate the molecular mechanisms underlying this modulation. Methods/Results: Using in vivo stationary microperfusion, we observed that fructose stimulates NHE3 mediated JHCO(3)(-) reabsorption. The MAPK pathway is not involved in this activation, as demonstrated by using of MEK/MAPK inhibitors, whereas experiments using a PKA inhibitor suggest that PKA inhibition plays a role in this response. These results were confirmed in vitro by measuring the cell pH recovery rate after NH4Cl pulse in LLC-PK1, a pig PT cell line, which showed reduced cAMP levels and NHE3 phosphorylation at serine-552 (PKA consensus site) after fructose treatment. Conclusions: NHE3 activity is stimulated by fructose, which increases proximal tubule Na+ reabsorption. The molecular mechanisms involved in this process are mediated, at least in part, by downregulation of the PKA signaling pathway. Future studies are needed to address whether fructose-stimulated NHE3 activity may contribute to renal injury and hypertension.
dc.description.indexMEDLINE
dc.description.sponsorshipFAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [2012/04150-4, 07/52945-8, 08/58287-5]
dc.description.sponsorshipCNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
dc.identifier.citationKIDNEY & BLOOD PRESSURE RESEARCH, v.36, n.1, p.320-334, 2012
dc.identifier.doi10.1159/000343390
dc.identifier.issn1420-4096
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/2630
dc.language.isoeng
dc.publisherKARGER
dc.relation.ispartofKidney & Blood Pressure Research
dc.rightsopenAccess
dc.rights.holderCopyright KARGER
dc.subjectFructose
dc.subjectIn situ microperfusion
dc.subjectcAMP
dc.subjectSodium hydrogen exchangers
dc.subjectLLC-PK1 cells
dc.subject.otherna+/h+ exchanger nhe3
dc.subject.otherprotein-kinase-a
dc.subject.othermetabolic syndrome
dc.subject.otherblood-pressure
dc.subject.otherinsulin-resistance
dc.subject.otherdietary fructose
dc.subject.otherph regulation
dc.subject.otherrat-kidney
dc.subject.othercells
dc.subject.otherhypertension
dc.subject.wosPhysiology
dc.subject.wosUrology & Nephrology
dc.subject.wosPeripheral Vascular Disease
dc.titleFructose Acutely Stimulates NHE3 Activity in Kidney Proximal Tubule
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalQUEIROZ-LEITE, Gabriella D.:Univ Sao Paulo, Sch Med, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508900 Sao Paulo, Brazil
hcfmusp.author.externalBEZERRA, Camila N. A.:Univ Sao Paulo, Sch Med, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508900 Sao Paulo, Brazil
hcfmusp.author.externalREBOUCAS, Nancy Amaral:Univ Sao Paulo, Sch Med, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508900 Sao Paulo, Brazil
hcfmusp.author.externalMALNIC, Gerhard:Univ Sao Paulo, Sch Med, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508900 Sao Paulo, Brazil
hcfmusp.citation.scopus27
hcfmusp.contributor.author-fmusphcCRAJOINAS, Renato O.
hcfmusp.contributor.author-fmusphcNERI, Elida A.
hcfmusp.contributor.author-fmusphcGIRARDI, Adriana C. C.
hcfmusp.description.beginpage320
hcfmusp.description.endpage334
hcfmusp.description.issue1
hcfmusp.description.volume36
hcfmusp.jcrKIDNEY BLOOD PRESS R
hcfmusp.origemWOS
hcfmusp.origem.pubmed23235337
hcfmusp.origem.scopus2-s2.0-84870727540
hcfmusp.origem.wosWOS:000318486400032
hcfmusp.publisher.cityBASEL
hcfmusp.publisher.countrySWITZERLAND
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hcfmusp.remissive.sponsorshipCNPq
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