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S-Nitrosoglutathione induces functional ?F508-CFTR in airway epithelial cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
2002 In: Biochem Biophys Res Commun., Vol. 297, 552-557 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 297, 552-557 p.
URN: urn:nbn:se:uu:diva-89968OAI: oai:DiVA.org:uu-89968DiVA: diva2:161956
Available from: 2002-10-11 Created: 2002-10-11Bibliographically approved
In thesis
1. Towards Pharmacological Treatment of Cystic Fibrosis
Open this publication in new window or tab >>Towards Pharmacological Treatment of Cystic Fibrosis
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

S-nitrosogluthatione is an endogenous substance, present at decreased levels in the lungs of CF patients and was recently found to induce mature CFTR in airway epithelial CF cell lines. We show that S-nitrosoglutathione in physiological concentrations increases the presence of ΔF508 CFTR in the cell membrane and induces cAMP dependent chloride transport in cystic fibrosis airway epithelial cells. The properties of S-nitrosoglutathione include other potential benefits for the CF patient and make this agent an interesting candidate for pharmacological treatment of CF that needs to be further evaluated.

Genistein was found to increase the chloride efflux in both normal and ΔF508 cells without stimulation of cAMP elevating agents and without prior treatment with phenylbutyrate. Genistein, in concentrations close to those that can be detected in plasma after a high soy diet, could induce chloride efflux in cells with the ΔF508 CFTR mutation and its possible use in the treatment of CF should therefore be further investigated.

Studies on nasal epithelial cells from CF patients showed cAMP dependent chloride efflux in some of the patients with severe genotypes. This may complicate in vitro evaluation of clinical treatment of these patients. The presence of cAMP dependent chloride transport did not necessarily lead to a milder phenotype. Other factors than CFTR may influence the clinical development of the disease.

Cystic fibrosis (CF) is the most common monogenetic disease among Caucasians. A defective cAMP regulated chloride channel (cystic fibrosis transmembrane conductance regulator, CFTR) in epithelial cells leads to viscous mucus, bacterial infections, inflammation and tissue damage in the lungs that cause death in 95% of the cystic fibrosis patients. There is no cure for the disease although existing treatment has dramatically prolonged the life expectancy. The aim of this thesis was to study pharmacological agents for their ability to restore the cellular deficiency in CF airway epithelial cells. X-ray microanalysis, MQAE fluorescence and immunocytochemistry were used to evaluate the effects.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 53 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1185
Cell biology, cystic fibrosis, airway epithelium, genotype, CFTR, chloride transport, genistein, phenotype, phenylbutyrate, S-nitrosoglutathione, Cellbiologi
National Category
Cell and Molecular Biology
Research subject
urn:nbn:se:uu:diva-2634 (URN)91-554-5409-7 (ISBN)
Public defence
2002-11-01, B21, BMC, Uppsala, 09:15
Available from: 2002-10-11 Created: 2002-10-11Bibliographically approved

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