S-Nitrosoglutathione induces functional DeltaF508-CFTR in airway epithelial cells |
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Authors: | Andersson Charlotte Gaston Benjamin Roomans Godfried M |
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Institution: | Department of Medical Cell Biology, Uppsala University, Box 571, SE-75123 Uppsala, Sweden. charlotte.andersson@medcellbiol.uu.se |
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Abstract: | S-Nitrosoglutathione (GSNO) is an endogenous bronchodilator levels of which are reduced in the airways of cystic fibrosis (CF) patients. GSNO has recently been shown to increase maturation of CFTR in CF cell lines at physiological concentrations. The ability of S-nitrosoglutathione to direct the DeltaF508-CFTR to the plasma membrane and restore the function of the cAMP-dependent chloride transport in cultured human airway epithelial cells has been studied. Immunocytochemistry showed a time- and dose-dependent increase of apically located CFTR after GSNO treatment. Chloride transport studies with the fluorescent dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) showed that GSNO was able to induce a fourfold increase of cAMP-dependent chloride transport. Our data and the fact that endogenous GSNO levels are lower in the airways of CF patients make GSNO an interesting candidate for pharmacological treatment of cystic fibrosis. |
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Keywords: | Cystic fibrosis Chloride transport CFTR S-Nitrosoglutathione Immunocytochemistry MQAE |
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