Dietary sodium intake regulates the ubiquitin-protein ligase nedd4-2 in the renal collecting system

Details

Serval ID
serval:BIB_BAB8E6192349
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dietary sodium intake regulates the ubiquitin-protein ligase nedd4-2 in the renal collecting system
Journal
Journal of the American Society of Nephrology
Author(s)
Loffing-Cueni  D., Flores  S. Y., Sauter  D., Daidie  D., Siegrist  N., Meneton  P., Staub  O., Loffing  J.
ISSN
1046-6673 (Print)
Publication state
Published
Issued date
05/2006
Volume
17
Number
5
Pages
1264-74
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Abstract
The activity of the epithelial sodium (Na(+)) channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) needs to be tightly regulated to match urinary Na(+) excretion with dietary Na(+) intake. The ubiquitin-protein ligase Nedd4-2, which in vitro interacts with ENaC subunits and reduces ENaC cell surface abundance and activity by ubiquitylation of the channel, may participate in the control of ENaC. This study confirms in vivo by reverse-transcriptase-PCR that Nedd4-2 is expressed throughout the nephron and is detectable by immunoblotting in kidney extracts. By immunohistochemistry, Nedd4-2 was found to be strongly expressed in the ASDN, with low staining intensity in the late distal convoluted tubule and early connecting tubule (where apical ENaC is high) and gradually increasing detection levels toward the collecting duct (CD; where apical ENaC is low). Compared with high-Na(+) diet (5% Na(+)), 2 wk of low-Na(+) diet (0.01% Na(+)) drastically reduces Nedd4-2 immunostaining and increases apical ENaC abundance in ASDN. Reduced Nedd4-2 immunostaining is not dependent on increased apical Na(+) entry in the CD, because it is similarly observed in mice with intact and with suppressed apical ENaC activity in the CD. Consistent with a role of mineralocorticoid hormones in the long-term regulation of Nedd4-2, 5-d treatment of cultured CD (mpkCCD(cl4)) cells with 1 microM aldosterone leads to reduction of Nedd4-2 protein expression. It is concluded that Nedd4-2 abundance is regulated by Na(+) diet, by a mechanism that likely involves aldosterone. This regulation may contribute to adaptation of apical ENaC activity to altered Na(+) intake.
Keywords
Animals Cells, Cultured Gene Expression Regulation/physiology Kidney Tubules, Collecting/*metabolism Male Mice Random Allocation Rats Rats, Sprague-Dawley Sodium, Dietary/*metabolism Species Specificity Tissue Distribution Ubiquitin-Protein Ligases/*metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 13:03
Last modification date
20/08/2019 15:28
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