title: Hormone-regulated transepithelial Na+ transport in mammalian CCD cells requires SGK1 expression.
abstract: To study the role of serum and glucocorticoid-inducible kinase-1 (SGK1) in mammalian cells, we compared Na(+) transport rates in wild-type (WT) M1 cortical collecting duct cells with M1 populations stably expressing human full-length SGK1, NH(2)-terminal truncated (DeltaN-60) SGK1, "kinase-dead" (K127M) SGK1, and cells that have downregulated levels of SGK1 mRNA (antisense SGK1). Basal rates of transepithelial Na(+) transport were highest in full-length SGK1 populations, compared among the above populations. Dexamethasone treatment increased Na(+) transport in WT and full-length SGK1 cells 2.7- and 2-fold, respectively. Modest stimulation of Na(+) absorption was detected after dexamethasone treatment in DeltaN-60 SGK1 populations. However, DeltaN-60 SGK1 transport rates remained substantially lower than WT values. Importantly, a combination of high insulin, dexamethasone, and serum failed to significantly stimulate Na(+) transport in antisense or K127M SGK1 cells. Additionally, expression of antisense SGK1 significantly decreased transepithelial resistance values. Overall, we concluded that SGK1 is a critical component in corticosteroid-regulated Na(+) transport in mammalian cortical collecting duct cells. Furthermore, our data suggest that the NH(2) terminus of SGK1 may contain a Phox homology-like domain that may be necessary for effective Na(+) transport.
authors.affiliation: Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA.
authors.forename: My N
authors.initials: MN
authors.lastname: Helms
authors.forename: Geza
authors.initials: G
authors.lastname: Fejes-Toth
authors.forename: Aniko
authors.initials: A
authors.lastname: Naray-Fejes-Toth
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002460:Cell Line; D002999:Clone Cells; D003907:Dexamethasone / Q000494:pharmacology; D004594:Electrophysiology; D053503:Epithelial Sodium Channels; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D017874:Immediate-Early Proteins; D007328:Insulin / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008353:Mannitol / Q000493:pharmacokinetics; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017384:Sequence Deletion; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D014162:Transfection; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D001798:Blood Proteins; D003907:Dexamethasone; D053503:Epithelial Sodium Channels; D005938:Glucocorticoids; D017874:Immediate-Early Proteins; D007328:Insulin; D008353:Mannitol; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012964:Sodium; D015222:Sodium Channels; D000099184:Serum-Glucocorticoid Regulated Kinases