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1 Division of Nephrology, Department of Pediatrics, and 2 Division of Nephrology, Departments of Medicine and of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143-0532; and 3 Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97201
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.
serum and glucocorticoid-regulated kinase; osmoregulation; sodium transport; phosphatidylinositol-3-kinase; epithelial sodium channel
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