HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/F505    most recent 00242.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Boyd, C. Articles by Náray-Fejes-Tóth, A. Search for Related Content PubMed PubMed Citation Articles by Boyd, C. Articles by Náray-Fejes-Tóth, A.

Gene regulation of ENaC subunits by serum- and glucocorticoid-inducible kinase-1

Dartmouth Medical School, Lebanon, New Hampshire

Submitted 29 June 2004 ; accepted in final form 7 November 2004

Aldosterone is a key regulator of epithelial Na⁺ channels (ENaC) in renal cortical collecting ducts (CCD). The goal of this study was to examine whether serum- and glucocorticoid-inducible kinase-1 (SGK1), an aldosterone-induced gene, is vital to the delayed effect of aldosterone by increasing the gene expression of ENaC subunits. To test this hypothesis, we compared the levels of ENaC mRNA in mouse CCD cells that stably express either full-length (FL)-SGK1 or a kinase-dead dominant negative (K127M)-SGK1. Our results revealed that SGK1 regulates gene expression of ENaC, whether cells are maintained in steroid-free media or in the presence of corticosteroids (CS) and/or other growth factors. Under all conditions, the loss of function of SGK1 caused a significant decrease in the expression of - and -ENaC, but not -ENaC. Compared with cells expressing FL-SGK1, K127M-SGK1 decreased the expression of - and -subunit mRNA by 45 and 90%, respectively. Next, to determine whether SGK1 is one of the proteins mediating the induction of -ENaC mRNA by CS, we compared steroid induction of -ENaC in cells expressing K127M-SGK1 vs. FL-SGK1. The maximum level of -ENaC mRNA levels following CS was significantly (45%) higher in FL-SGK1- vs. K127M-SGK1-expressing cells, although the fold-induction by CS was similar in both FL-SGK1- and K127M-SGK1-expressing cells. In summary, we report for the first time that SGK1 regulates transcription of ENaC subunits. We propose that the effect of SGK1 on ENaC transcription is mediated by the activation of unidentified transcription factors.

aldosterone; transcriptional regulation; cortical collecting ducts; sodium transport; epithelial sodium channel

This article has been cited by other articles:

				A. Naray-Fejes-Toth, C. Boyd, and G. Fejes-Toth Regulation of epithelial sodium transport by promyelocytic leukemia zinc finger protein Am J Physiol Renal Physiol, July 1, 2008; 295(1): F18 - F26. [Abstract] [Full Text] [PDF]

				G. Fejes-Toth, G. Frindt, A. Naray-Fejes-Toth, and L. G. Palmer Epithelial Na+ channel activation and processing in mice lacking SGK1 Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1298 - F1305. [Abstract] [Full Text] [PDF]

				A. Taruno, N. Niisato, and Y. Marunaka Intracellular calcium plays a role as the second messenger of hypotonic stress in gene regulation of SGK1 and ENaC in renal epithelial A6 cells Am J Physiol Renal Physiol, January 1, 2008; 294(1): F177 - F186. [Abstract] [Full Text] [PDF]

				R. F. Husted, K. A. Volk, R. D. Sigmund, and J. B. Stokes Discordant effects of corticosteroids and expression of subunits on ENaC activity Am J Physiol Renal Physiol, September 1, 2007; 293(3): F813 - F820. [Abstract] [Full Text] [PDF]

				J. A. Martel, D. Michael, G. Fejes-Toth, and A. Naray-Fejes-Toth Melanophilin, a novel aldosterone-induced gene in mouse cortical collecting duct cells Am J Physiol Renal Physiol, September 1, 2007; 293(3): F904 - F913. [Abstract] [Full Text] [PDF]

				A. Dagenais, R. Frechette, M.-E. Clermont, C. Masse, A. Prive, E. Brochiero, and Y. Berthiaume Dexamethasone inhibits the action of TNF on ENaC expression and activity Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1220 - L1231. [Abstract] [Full Text] [PDF]

				F. Lang, C. Bohmer, M. Palmada, G. Seebohm, N. Strutz-Seebohm, and V. Vallon (Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms. Physiol Rev, October 1, 2006; 86(4): 1151 - 1178. [Abstract] [Full Text] [PDF]

				W. Zhang, X. Xia, D. I. Jalal, T. Kuncewicz, W. Xu, G. D. Lesage, and B. C. Kone Aldosterone-sensitive repression of ENaC{alpha} transcription by a histone H3 lysine-79 methyltransferase Am J Physiol Cell Physiol, March 1, 2006; 290(3): C936 - C946. [Abstract] [Full Text] [PDF]

				M. N. Helms, L. Yu, B. Malik, D. J. Kleinhenz, C. M. Hart, and D. C. Eaton Role of SGK1 in nitric oxide inhibition of ENaC in Na+-transporting epithelia Am J Physiol Cell Physiol, September 1, 2005; 289(3): C717 - C726. [Abstract] [Full Text] [PDF]