PMID- 18268134
OWN - NLM
STAT- MEDLINE
DCOM- 20080311
LR  - 20171116
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 51
IP  - 3
DP  - 2008 Mar
TI  - Expression, transcription, and possible antagonistic interaction of the human 
      Nedd4L gene variant: implications for essential hypertension.
PG  - 773-7
LID - 10.1161/HYPERTENSIONAHA.107.102061 [doi]
AB  - Net sodium balances in humans are maintained through various ion transporters 
      expressed along the entire nephron. Among these ion transporters, epithelial 
      sodium channels (ENaC) located along the aldosterone-sensitive distal nephron 
      (ASDN) play a pivotal role in the homeostasis of sodium balance. This is 
      supported by analyses of inherited hypertensive disorders, showing that genes 
      encoding ENaC and other modulatory proteins cause hereditary hypertension, such 
      as Liddle syndrome. Among various modulating proteins, E3 ubiquitin ligase, 
      Nedd4L, binds the PY motif of ENaC COOH terminals and catalyzes ubiquitination of 
      the NH(2) terminus of the protein for subsequent degradation. Both evolutionarily 
      conserved and evolutionarily new C2 domains of human Nedd4L, a cryptic splice 
      variant resulting in a disrupted isoform product formed by a frame-shift 
      mutation, were reported previously. We focused on one of the isoforms, isoform I, 
      generated by SNP (rs4149601), and studied its expression and interactions with 
      other isoforms by molecular biological, immunohistochemical, and 
      electrophysiological methods. We found that isoform I may interact with other 
      human isoforms in a dominant-negative fashion. Such interactions might abnormally 
      increase sodium reabsorption. Taken together, our analyses suggest that the human 
      Nedd4L gene, especially the evolutionarily new isoform I, is a candidate gene for 
      hypertension.
FAU - Araki, Naomi
AU  - Araki N
AD  - Department of Medical Science and Cardio-Renal Medicine, Yokohama City University 
      Graduate School of Medicine, Kanagawa-ken, Japan.
FAU - Umemura, Masanari
AU  - Umemura M
FAU - Miyagi, Yohei
AU  - Miyagi Y
FAU - Yabana, Machiko
AU  - Yabana M
FAU - Miki, Yuko
AU  - Miki Y
FAU - Tamura, Koichi
AU  - Tamura K
FAU - Uchino, Kazuaki
AU  - Uchino K
FAU - Aoki, Reina
AU  - Aoki R
FAU - Goshima, Yoshio
AU  - Goshima Y
FAU - Umemura, Satoshi
AU  - Umemura S
FAU - Ishigami, Tomoaki
AU  - Ishigami T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080211
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Xenopus Proteins)
RN  - EC 2.3.2.26 (Nedd4 Ubiquitin Protein Ligases)
RN  - EC 2.3.2.26 (Nedd4L protein, human)
RN  - EC 2.3.2.26 (nedd4l protein, Xenopus)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Brain/metabolism/pathology
MH  - Cells, Cultured
MH  - Colon/metabolism/pathology
MH  - Electrophysiology
MH  - Endosomal Sorting Complexes Required for Transport
MH  - Female
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Hypertension/*genetics/physiopathology
MH  - Kidney/metabolism/pathology
MH  - Liver/metabolism/pathology
MH  - Lung/metabolism/pathology
MH  - Nedd4 Ubiquitin Protein Ligases
MH  - Patch-Clamp Techniques
MH  - Protein Isoforms/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Transcription, Genetic/*physiology
MH  - Ubiquitin-Protein Ligases/*genetics/metabolism
MH  - Xenopus Proteins
MH  - Xenopus laevis
EDAT- 2008/02/13 09:00
MHDA- 2008/03/12 09:00
CRDT- 2008/02/13 09:00
PHST- 2008/02/13 09:00 [pubmed]
PHST- 2008/03/12 09:00 [medline]
PHST- 2008/02/13 09:00 [entrez]
AID - HYPERTENSIONAHA.107.102061 [pii]
AID - 10.1161/HYPERTENSIONAHA.107.102061 [doi]
PST - ppublish
SO  - Hypertension. 2008 Mar;51(3):773-7. doi: 10.1161/HYPERTENSIONAHA.107.102061. Epub 
      2008 Feb 11.