title: Hypotonic induction of SGK1 and Na+ transport in A6 cells.
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.
authors.affiliation: Division of Nephrology, Department of Pediatrics, University of California, San Francisco, California 94143-0532, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Rozansky
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Ninh
authors.initials: N
authors.lastname: Doan
authors.forename: Timothy
authors.initials: T
authors.lastname: Purdy
authors.forename: Tonya
authors.initials: T
authors.lastname: Faulk
authors.forename: Aditi
authors.initials: A
authors.lastname: Bhargava
authors.forename: Kevin
authors.initials: K
authors.lastname: Dawson
authors.forename: David
authors.initials: D
authors.lastname: Pearce
mesh_terms: D000818:Animals; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053503:Epithelial Sodium Channels; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006982:Hypertonic Solutions / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology*; D017874:Immediate-Early Proteins; D009025:Morpholines / Q000494:pharmacology; D009687:Nuclear Proteins; D009997:Osmotic Pressure; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D017874:Immediate-Early Proteins; D009025:Morpholines; D009687:Nuclear Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012964:Sodium; D015222:Sodium Channels; D000099184:Serum-Glucocorticoid Regulated Kinases; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one