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

Autor(es)

Crajoinas, R. O. ^[1] ; Pessoa, T. D. ^[2] ; Rodrigues, M. V. ^[1] ; Malnic, G. ^[2] ; Girardi, A. C. C. ^[1]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: ACTA PHYSIOLOGICA; v. 211, n. 2, p. 395-408, JUN 2014.
• Citações Web of Science: 6

Resumo

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)

• Processo FAPESP: 07/52945-8 - Importância do peptídeo semelhante ao glucagon 1 (GLP-1) na manutenção do volume extracelular: abordagem funcional, farmacológica e molecular
• Beneficiário: Adriana Castello Costa Girardi
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
• Processo FAPESP: 12/10146-0 - Mecanismos moleculares da regulação da função tubular proximal na hipertensão arterial
• Beneficiário: Adriana Castello Costa Girardi
• Linha de fomento: Auxílio à Pesquisa - Regular