Aldosterone regulates Na+, K+ ATPase activity in human renal proximal tubule cells through mineralocorticoid receptor

Sarah A. Salyer, Jason Parks, Michelle T. Barati, Eleanor D. Lederer, Barbara J. Clark, Janet D. Klein, Syed J. Khundmiri

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The mechanisms by which aldosterone increases Na+, K+ ATPase and sodium channel activity in cortical collecting duct and distal nephron have been extensively studied. Recent investigations demonstrate that aldosterone increases Na-H exchanger-3 (NHE-3) activity, bicarbonate transport, and H+ ATPase in proximal tubules. However, the role of aldosterone in regulation of Na+, K+ ATPase in proximal tubules is unknown. We hypothesize that aldosterone increases Na+, K+ ATPase activity in proximal tubules through activation of the mineralocorticoid receptor (MR). Immunohistochemistry of kidney sections from human, rat, and mouse kidneys revealed that the MR is expressed in the cytosol of tubules staining positively for Lotus tetragonolobus agglutinin and type IIa sodium-phosphate cotransporter (NpT2a), confirming proximal tubule localization. Adrenalectomy in Sprague-Dawley rats decreased expression of MR, ENaC α, Na+, K+ ATPase α1, and NHE-1 in all tubules, while supplementation with aldosterone restored expression of above proteins. In human kidney proximal tubule (HKC11) cells, treatment with aldosterone resulted in translocation of MR to the nucleus and phosphorylation of SGK-1. Treatment with aldosterone also increased Na+, K+ ATPase-mediated 86Rb uptake and expression of Na+, K+ ATPase α1 subunits in HKC11 cells. The effects of aldosterone on Na+, K+ ATPase-mediated 86Rb uptake were prevented by spironolactone, a competitive inhibitor of aldosterone for the MR, and partially by Mifepristone, a glucocorticoid receptor (GR) inhibitor. These results suggest that aldosterone regulates Na+, K+ ATPase in renal proximal tubule cells through an MR-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)2143-2152
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number10
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

Keywords

  • Aldosterone
  • K ATPase
  • Mineralocorticoid receptor
  • Na
  • Proximal tubule
  • Sodium and glucocorticoid-dependent kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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