PMID- 16571785
OWN - NLM
STAT- MEDLINE
DCOM- 20061102
LR  - 20171116
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 17
IP  - 5
DP  - 2006 May
TI  - Dietary sodium intake regulates the ubiquitin-protein ligase nedd4-2 in the renal 
      collecting system.
PG  - 1264-74
AB  - 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.
FAU - Loffing-Cueni, Dominique
AU  - Loffing-Cueni D
AD  - University of Fribourg, Department of Medicine-Anatomy, Route Albert Gockel 1, 
      CH-1700 Fribourg, Switzerland.
FAU - Flores, Sandra Y
AU  - Flores SY
FAU - Sauter, Daniel
AU  - Sauter D
FAU - Daidie, Dorothee
AU  - Daidie D
FAU - Siegrist, Nicole
AU  - Siegrist N
FAU - Meneton, Pierre
AU  - Meneton P
FAU - Staub, Olivier
AU  - Staub O
FAU - Loffing, Johannes
AU  - Loffing J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060329
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (Sodium, Dietary)
RN  - EC 2.3.2.26 (NEDD4L protein, rat)
RN  - EC 2.3.2.26 (Nedd4 Ubiquitin Protein Ligases)
RN  - EC 2.3.2.26 (Nedd4 protein, rat)
RN  - EC 2.3.2.26 (Nedd4l protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Endosomal Sorting Complexes Required for Transport
MH  - Gene Expression Regulation/physiology
MH  - Kidney Tubules, Collecting/*metabolism
MH  - Male
MH  - Mice
MH  - Nedd4 Ubiquitin Protein Ligases
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium, Dietary/*metabolism
MH  - Species Specificity
MH  - Tissue Distribution
MH  - Ubiquitin-Protein Ligases/*metabolism
EDAT- 2006/03/31 09:00
MHDA- 2006/11/03 09:00
CRDT- 2006/03/31 09:00
PHST- 2006/03/31 09:00 [pubmed]
PHST- 2006/11/03 09:00 [medline]
PHST- 2006/03/31 09:00 [entrez]
AID - ASN.2005060659 [pii]
AID - 10.1681/ASN.2005060659 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2006 May;17(5):1264-74. doi: 10.1681/ASN.2005060659. Epub 2006 
      Mar 29.