Akt2/PKBβ-sensitive regulation of renal phosphate transport.

Autor: Kempe, D. S., Ackermann, T. F., Boini, K. M., Klaus, F., Umbach, A. T., Dërmaku-Sopjani, M., Judenhofer, M. S., Pichler, B. J., Capuano, P., Stange, G., Wagner, C. A., Birnbaum, M. J., Pearce, D., Föller, M., Lang, F.
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Zdroj: Acta Physiologica; Sep2010, Vol. 200 Issue 1, p75-85, 11p, 1 Black and White Photograph, 1 Chart, 5 Graphs
Abstrakt: Aim: The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport. Methods: The renal phosphate transporter NaPi-IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na+ phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBβ knockout mice ( akt2 −/−) and corresponding wild-type mice ( akt2 +/+). Transporter protein abundance was determined using Western blotting and phosphate transport by 32P uptake into brush border membrane vesicles. Results: The phosphate-induced current in NaPi-IIa-expressing Xenopus oocytes was significantly increased by the coexpression of Akt/PKB. Phosphate excretion [μmol per 24 h per g BW] was higher by 91% in akt2 −/− than in akt2 +/+ mice. The phosphaturia of akt2 −/− mice occurred despite normal transport activity and expression of the renal phosphate transporters NaPi-IIa, NaPi-IIc and Pit2 in the brush border membrane, a significantly decreased plasma PTH concentration (by 46%) and a significantly enhanced plasma 1,25-dihydroxyvitamin D3 concentration (by 46%). Moreover, fractional renal Ca2+ excretion was significantly enhanced (by 53%) and bone density significantly reduced (by 11%) in akt2 −/− mice. Conclusions: Akt2/PKBβ plays a role in the acute regulation of renal phosphate transport and thus contributes to the maintenance of phosphate balance and adequate mineralization of bone. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index