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1 Pulmonary Division, University of Sherbrooke, Sherbrooke, Quebec, Canada
2 Department of Physiology, McGill University, Montreal, Quebec, Canada
* To whom correspondence should be addressed. E-mail: Andre.Cantin{at}USherbrooke.ca.
Epithelial mucous membranes are repeatedly exposed to oxidants and xenobiotics. Cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in glutathione trans-epithelial flux, and in defining the hydration and viscoelasticity of protective mucus. We thus hypothesized that CFTR expression and function may be modulated by oxidant stress. A sub-lethal oxidant stress (tert-butylhydroquinone, tBHQ) in CFTR expressing epithelial cells (T84) induced a significant increase in cellular glutathione that was associated with an increase in the expression of the gene encoding the heavy subunit of the rate-limiting enzyme for glutathione synthesis, 
-glutamylcysteine synthetase (GCShs). CFTR gene expression was markedly decreased according to a time-course that mirrored the changes in 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, tBHQ increased 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.
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