Hypotonic induction of SGK1 and Na+ transport in A6 cells

David J. Rozansky, Jian Wang, Ninh Doan, Timothy Purdy, Tonya Faulk, Aditi Bhargava, Kevin Dawson, David Pearce

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Serum and glucocorticoid-regulated kinase-1 (SGK1) is a serine-threonine kinase that is regulated at the transcriptional level by numerous regulatory inputs, including mineralocorticoids, glucocorticoids, follicle-stimulating hormone, and osmotic stress. In the distal nephron, SGK1 is induced by aldosterone and regulates epithelial Na+ channel-mediated transepithelial Na+ transport. In other tissues, including liver and shark rectal gland, SGK1 is regulated by hypertonic stress and is thought to modulate epithelial Na+ channel- and Na+-K+-2Cl- cotransporter-mediated Na+ transport. In this report, we examined the regulation of SGK1 mRNA and protein expression and Na+ currents in response to osmotic stress in A6 cells, a cultured cell line derived from Xenopus laevis distal nephron. We found that in contrast to hepatocytes and rectal gland cells, hypotonic conditions stimulated SGK1 expression and Na+ transport in A6 cells. Moreover, a correlation was found between SGK1 induction and the later phase of activation of Na+ transport in response to hypotonic treatment. When A6 cells were pretreated with an inhibitor of phosphatidylinositol 3-kinase (PI3K), Na+ transport was blunted and only inactive forms of SGK1 were expressed. Surprisingly, these results demonstrate that both hypertonic and hypotonic stimuli can induce SGK1 gene expression in a cell type-dependent fashion. Moreover, these data lend support to the view that SGK1 contributes to the defense of extracellular fluid volume and tonicity in amphibia by mediating a component of the hypotonic induction of distal nephron Na+ transport.

Original languageEnglish (US)
Pages (from-to)F105-F113
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number1 52-1
DOIs
StatePublished - 2002

Keywords

  • Epithelial sodium channel
  • Osmoregulation
  • Phosphatidylinositol-3-kinase
  • Serum and glucocorticoid-regulated kinase
  • Sodium transport

ASJC Scopus subject areas

  • Physiology
  • Urology

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