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Original Paper

Control of Basal CFTR Gene Expression by Bicarbonate-Sensitive Adenylyl Cyclase in Human Pulmonary Cells

Baudouin-Legros M. · Hamdaoui N. · Borot F. · Fritsch J. · Ollero M. · Planelles G.1 · Edelman A.1

Author affiliations

Inserm, U845, Paris, F-75015, Université Paris V-Paris Descartes, Faculté de Médecine René Descartes, Paris, F-75075, France

Corresponding Author

Maryvonne Baudouin-Legros

Faculté de Médecine René Descartes

156 rue de Vaugirard, 75015 Paris (France)

Tel. +33 0140615621, Fax: +33 0140615591

E-Mail legroscommat;necker.fr

Related Articles for ""

Cell Physiol Biochem 2008;21:075–086

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Abstract

The CFTR protein, encoded by the gene whose mutations induce Cystic Fibrosis, is an anion channel devoted mainly to chloride and bicarbonate transmembrane transport, but which also regulates transport of several other ions. Moreover, it is implicated in the cell response to inflammation, and, reciprocally, cftr gene expression is modulated by inflammatory stimuli and transduction pathways. Looking for a control of CFTR expression by ionic conditions, we investigated the effect of altered extracellular bicarbonate ion concentration on CFTR expression in human pulmonary Calu-3 cells. We found that basal cftr gene transcription is enhanced when extracellular HCO3- concentration increases from 0 to 25 mmol/l. The transduction pathway controlled by these extracellular [HCO3-] variations includes cAMP production linked to the stimulation of soluble adenylyl cyclase (sAC), and nuclear accumulation of the transcription factor, CREB. Basal membrane content in CFTR protein exhibits the same variations as cftr mRNA in cells incubated in the presence of extracellular [HCO3-] between 0 and 25 mmol/l, and is also decreased by inhibiting sAC in the presence of HCO3-. These results show that bicarbonate-controlled sAC stimulation must be taken into account in cell physiology and that basal CFTR expression depends on an ionic parameter.

© 2008 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: October 26, 2007
Published online: January 16, 2008
Issue release date: January 2008

Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: https://www.karger.com/CPB


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