Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation

Details

Serval ID
serval:BIB_F6C4EC8F677D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation
Journal
Journal of the American Society of Nephrology
Author(s)
Fakitsas  P., Adam  G., Daidie  D., van Bemmelen  M. X., Fouladkou  F., Patrignani  A., Wagner  U., Warth  R., Camargo  S. M., Staub  O., Verrey  F.
ISSN
1046-6673 (Print)
Publication state
Published
Issued date
04/2007
Volume
18
Number
4
Pages
1084-92
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Abstract
The mineralocorticoid hormone aldosterone controls sodium reabsorption and BP largely by regulating the cell-surface expression and function of the epithelial sodium channel (ENaC) in target kidney tubules. Part of the stimulatory effect of aldosterone on ENaC is mediated by the induction of serum- and glucocorticoid-regulated kinase 1 (Sgk1), a kinase that interferes with the ubiquitylation of ENaC by ubiquitin-protein ligase Nedd4-2. In vivo early aldosterone-regulated mRNA now has been identified in microselected mouse distal nephron by microarray. From 22 mRNA that displayed a two-fold or more change, 13 were downregulated and nine were upregulated. Besides Sgk1, the induced mRNA include Grem2 (protein related to DAN and cerebrus [PRDC]), activating transcription factor 3, cAMP responsive element modulator, and the ubiquitin-specific protease Usp2-45. The induction of this last enzyme isoform was verified in mouse distal nephron tubule at the protein level. With the use of Hek293 cells, Xenopus oocytes, and mpkCCD(c14) cells as expression systems, it was shown that Usp2-45 deubiquitylates ENaC and stimulates ENaC-mediated sodium transport, an effect that is not additive to that of Sgk1. A deubiquitylating enzyme that targets ENaC in vitro and thus may play a role in sodium transport regulation was identified within a series of new in vivo early aldosterone-regulated gene products.
Keywords
Aldosterone/*pharmacology Animals Endopeptidases/genetics/*physiology Epithelial Sodium Channel/*metabolism Female Gene Expression Regulation/drug effects Mice Mice, Inbred C57BL Oligonucleotide Array Sequence Analysis Ubiquitin/*metabolism
Pubmed
Web of science
Create date
24/01/2008 13:03
Last modification date
20/08/2019 16:23
Usage data