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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Changes in the activity and expression of protein phosphatase-1 accompany the differential regulation of NHE3 before and after the onset of hypertension in spontaneously hypertensive rats

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Crajoinas, R. O. [1] ; Pessoa, T. D. [2] ; Rodrigues, M. V. [1] ; Malnic, G. [2] ; Girardi, A. C. C. [1]
Total Authors: 5
[1] Univ Sao Paulo, Sch Med, Lab Genet & Mol Cardiol, Heart Inst InCor, BR-05403900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05403900 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: ACTA PHYSIOLOGICA; v. 211, n. 2, p. 395-408, JUN 2014.
Web of Science Citations: 6

AimThe Na+/H+ exchanger NHE3 activity decreases in the proximal tubule of spontaneously hypertensive rats (SHRs) as blood pressure increases, and this reduction is correlated with higher NHE3 phosphorylation levels at the PKA consensus site serine 552. This study tested the hypothesis that this lowered NHE3 activity is associated with an increase in PKA activity and expression, and/or a decrease in protein phosphatase-1 (PP1) activity and expression. MethodsProximal tubule NHE3 activity was measured as the rate of bicarbonate reabsorption by stationary microperfusion. NHE3 phosphorylation and protein expression were determined by immunoblotting. PKA and PP1 activities were determined using specific substrates under optimal enzymatic conditions. ResultsThe PKA activator, 6-MB-cAMP, increased the phosphorylation levels of NHE3 at serine 552 in the renal cortex; this increase happens to a much greater extent in young pre-hypertensive SHRs (Y-SHRs) compared to adult SHRs with established hypertension (A-SHRs). Likewise, the inhibitory effect of 6-MB-cAMP on NHE3 transport activity was much more pronounced in the proximal tubules of Y-SHRs than in those of A-SHRs. Renal cortical activity of PKA was not significantly different between Y-SHRs and A-SHRs. On the other hand, Y-SHRs exhibited higher protein phosphatase 1 (PP1) activity, and their expression of the PP1 catalytic subunit PP1 in the renal cortex was also higher than in A-SHRs. ConclusionCollectively, these results support the idea that the lower NHE3 transport activity and higher phosphorylation occurring after the development of hypertension in SHRs are due, at least in part, to reduced PP1-mediated dephosphorylation of NHE3 at serine 552. (AU)

FAPESP's process: 12/10146-0 - Molecular mechanisms of regulation of the proximal tubular function in hypertension
Grantee:Adriana Castello Costa Girardi
Support type: Regular Research Grants