Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR

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dc.contributor.authorCrajoinas, Renato O.
dc.contributor.authorLessa, Lucilia M. A.
dc.contributor.authorCarraro-Lacroix, Luciene R. [UNIFESP]
dc.contributor.authorDavel, Ana Paula C.
dc.contributor.authorPacheco, Bruna P. M.
dc.contributor.authorRossoni, Luciana V.
dc.contributor.authorMalnic, Gerhard
dc.contributor.authorGirardi, Adriana C. C.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:05:29Z
dc.date.available2016-01-24T14:05:29Z
dc.date.issued2010-10-01
dc.description.abstractCrajoinas RO, Lessa LMA, Carraro-Lacroix LR, Davel APC, Pacheco BPM, Rossoni LV, Malnic G, Girardi ACC. Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR. Am J Physiol Renal Physiol 299:F872-F881, 2010. First published July 14, 2010; doi:10.1152/ajprenal.00654.2009.-Abnormalities in renal proximal tubular (PT) sodium transport play an important role in the pathophysiology of essential hypertension. the Na(+)/H(+) exchanger isoform 3 (NHE3) represents the major route for sodium entry across the apical membrane of renal PT cells. We therefore aimed to assess in vivo NHE3 transport activity and to define the molecular mechanisms underlying NHE3 regulation before and after development of hypertension in the spontaneously hypertensive rat (SHR). NHE3 function was measured as the rate of bicarbonate reabsorption by means of in vivo stationary microperfusion in PT from young prehypertensive SHR (Y-SHR; 5-wk-old), adult SHR (A-SHR; 14-wk-old), and age-matched Wistar Kyoto (WKY) rats. We found that NHE3-mediated PT bicarbonate reabsorption was reduced with age in the SHR (1.08 +/- 0.10 vs. 0.41 +/- 0.04 nmol/cm(2)xs), while it was increased in the transition from youth to adulthood in the WKY rat (0.59 +/- 0.05 vs. 1.26 +/- 0.11 nmol/cm(2)xs). Higher NHE3 activity in the Y-SHR compared with A-SHR was associated with a predominant microvilli confinement and a lower ratio of phosphorylated NHE3 at serine-552 to total NHE3 (P-NHE3/total). After development of hypertension, P-NHE3/total increased and NHE3 was retracted out of the microvillar microdomain along with the regulator dipeptidyl peptidase IV (DPPIV). Collectively, our data suggest that the PT is playing a role in adapting to the hypertension in the SHR. the molecular mechanisms of this adaptation possibly include an increase of P-NHE3/total and a redistribution of the NHE3-DPPIV complex from the body to the base of the PT microvilli, both predicted to decrease sodium reabsorption.en
dc.description.affiliationUniv São Paulo, Sch Med, Heart Inst InCor, BR-05403900 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05403900 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Physiol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Physiol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extentF872-F881
dc.identifierhttp://dx.doi.org/10.1152/ajprenal.00654.2009
dc.identifier.citationAmerican Journal of Physiology-renal Physiology. Bethesda: Amer Physiological Soc, v. 299, n. 4, p. F872-F881, 2010.
dc.identifier.doi10.1152/ajprenal.00654.2009
dc.identifier.issn1931-857X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32925
dc.identifier.wosWOS:000282484000023
dc.language.isoeng
dc.publisherAmer Physiological Soc
dc.relation.ispartofAmerican Journal of Physiology-renal Physiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectsodium transporten
dc.subjectproximal tubuleen
dc.subjectblood pressureen
dc.subjectphosphorylationen
dc.subjectdipeptidyl peptidase IVen
dc.titlePosttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHRen
dc.typeinfo:eu-repo/semantics/article
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