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Am J Physiol Cell Physiol. 2006 Jan;290(1):C262-70. Epub 2005 Sep 14.

Oxidant stress suppresses CFTR expression.

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  • 1Pulmonary Research Unit, Faculty of Medicine, Univ. of Sherbrooke, 3001, 12ième Ave. Nord, Sherbrooke, QC, Canada J1H 5N4. Andre.Cantin@USherbrooke.ca

Abstract

Epithelial mucous membranes are repeatedly exposed to oxidants and xenobiotics. CFTR plays a role in glutathione transepithelial flux and in defining the hydration and viscoelasticity of protective mucus. We therefore hypothesized that CFTR expression and function may be modulated by oxidant stress. A sublethal oxidant stress (tert-butylhydroquinone, BHQ) in CFTR-expressing epithelial cells (T84) induced a significant increase in cellular glutathione that was associated with an increase in expression of the gene encoding the heavy subunit of the rate-limiting enzyme for glutathione synthesis, gamma-glutamylcysteine synthetase (gamma-GCShs). CFTR gene expression was markedly decreased according to a time course that mirrored the changes in gamma-GCShs. Western blot analysis confirmed that the decrease in CFTR gene expression was associated with a decrease in CFTR protein. cAMP-dependent iodide efflux was also decreased by the oxidant stress. Nuclear run-on assays indicated that the oxidant stress had no effect on CFTR gene transcription, but the mRNA stability in the oxidant-stressed cells was markedly reduced. Furthermore, BHQ increased gamma-GCShs mRNA while decreasing CFTR mRNA in Calu-3 cells, and taurine chloramine induced similar effects in T84 cells. We conclude that suppression of CFTR expression may represent an adaptive response of mucosal epithelium to an exogenous oxidant stress.

PMID:
16162662
DOI:
10.1152/ajpcell.00070.2005
[PubMed - indexed for MEDLINE]
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