Document Detail

Regulation of endogenous ENaC functional expression by CFTR and ΔF508-CFTR in airway epithelial cells.
MedLine Citation:
PMID:  20935229     Owner:  NLM     Status:  MEDLINE    
The functional expression of the epithelial sodium channel (ENaC) appears elevated in cystic fibrosis (CF) airway epithelia, but the mechanism by which this occurs is not clear. We tested the hypothesis that the cystic fibrosis transmembrane conductance regulator (CFTR) alters the trafficking of endogenously expressed human ENaC in the CFBE41o⁻ model of CF bronchial epithelia. Functional expression of ENaC, as defined by amiloride-inhibited short-circuit current (I(sc)) in Ussing chambers, was absent under control conditions but present in CFBE41o⁻ parental and ΔF508-CFTR-overexpressing cells after treatment with 1 μM dexamethasone (Dex) for 24 h. The effect of Dex was mimicked by incubation with the glucocorticoid hydrocortisone but not with the mineralocorticoid aldosterone. Application of trypsin to the apical surface to activate uncleaved, "near-silent" ENaC caused an additional increase in amiloride-sensitive I(sc) in the Dex-treated cells and was without effect in the control cells, suggesting that Dex increased ENaC cell surface expression. In contrast, Dex treatment did not stimulate amiloride-sensitive I(sc) in CFBE41o⁻ cells that stably express wild-type (wt) CFTR. CFBE41o⁻ wt cells also had reduced expression of α- and γ-ENaC compared with parental and ΔF508-CFTR-overexpressing cells. Furthermore, application of trypsin to the apical surface of Dex-treated CFBE41o⁻ wt cells did not stimulate amiloride-sensitive I(sc), suggesting that ENaC remained absent from the surface of these cells even after Dex treatment. We also tested the effect of trafficking-corrected ΔF508-CFTR on ENaC functional expression. Incubation with 1 mM 4-phenylbutyrate synergistically increased Dex-induced ENaC functional expression in ΔF508-CFTR-overexpressing cells. These data support the hypothesis that wt CFTR can regulate the whole cell, functional, and surface expression of endogenous ENaC in airway epithelial cells and that absence of this regulation may foster ENaC hyperactivity in CF airway epithelia.
Ronald C Rubenstein; Shannon R Lockwood; Ellen Lide; Rebecca Bauer; Laurence Suaud; Yael Grumbach
Related Documents :
6831539 - Wound healing in the cornea of the chick embryo. v. an observation and quantitative ass...
1696389 - Plate and collagen-gel cultures of normal canine mammary epithelial cells.
7529009 - Identification of acid cysteine proteinase inhibitor (cystatin a) in the human thymus.
9358369 - Differential attachment of oral treponemes to monolayers of epithelial cells.
7814649 - Novel production of interleukin-1 receptor antagonist peptides in normal human cornea.
2477349 - Epithelial cell heterogeneity in mammalian thymus: monoclonal antibody to high molecula...
20460749 - Targeting the na(+)/k(+)-atpase alpha1 subunit of hepatoma hepg2 cell line to induce ap...
19051489 - Metabolism of daunomycin (nsc-82151) in vitro and the chemotherapeutic activity of isol...
12181429 - Arsenic trioxide produces polymerization of microtubules and mitotic arrest before apop...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-08
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  300     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-20     Completed Date:  2011-01-28     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L88-L101     Citation Subset:  IM    
The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Aldosterone / pharmacology,  therapeutic use
Amiloride / pharmacology
Cystic Fibrosis / drug therapy,  genetics*
Cystic Fibrosis Transmembrane Conductance Regulator / drug effects,  genetics,  pharmacology*
Dexamethasone / pharmacology,  therapeutic use
Epithelial Sodium Channels / drug effects,  genetics*
Gene Expression Regulation / drug effects*
Hydrocortisone / pharmacology,  therapeutic use
Sequence Deletion
Trypsin / pharmacology
Grant Support
Reg. No./Substance:
0/CFTR protein, human; 0/Epithelial Sodium Channels; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 2609-46-3/Amiloride; 50-02-2/Dexamethasone; 50-23-7/Hydrocortisone; 52-39-1/Aldosterone; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Inflammation in fetal sheep from intra-amniotic injection of Ureaplasma parvum.
Next Document:  Respiratory syncytial virus is associated with an inflammatory response in lungs and architectural r...