Pharmacological Treatment of Cystic Fibrosis

S-nitrosogluthatione is surely an endogenous substance, found at decreased levels in the lungs of CF patients and was not too long ago discovered to induce mature CFTR in airway epithelial CF cell lines. We reveal that S-nitrosoglutathione in physiological concentrations raises the existence of ΔF508 CFTR in the cell membrane and induces cAMP dependent chloride transport in cystic fibrosis airway epithelial cells. The properties of S-nitrosoglutathione consist of additional possible advantages for the CF patient making this agent a worthwhile candidate for pharmacological treatment of CF which should be further evaluated…..

Genistein was discovered to improve the chloride efflux in both normal and ΔF508 cells without stimulation of cAMP elevating agents and without prior treatment with phenylbutyrate. Genistein, in concentrations near to those which may be discovered in plasma following a high soy diet, could induce chloride efflux in cells with the ΔF508 CFTR mutation and its possible utilization in the treatment of CF should consequently be deeper investigated. Research on nasal epithelial cells from CF patients showed cAMP dependent chloride efflux in certain patients with serious genotypes. This tends to complicate in vitro examination of clinical treatment of these patients. The existence of cAMP dependent chloride transport do not always result in a milder phenotype……


1.1 Cystic fibrosis
1.2 Cystic fibrosis transmembrane conductance regulator
1.3 The airway epithelium
1.4 Airway ion transport
1.5 Signaling
1.6 Treatment of Cystic Fibrosis
1.6.1 Pharmacological treatment of cystic fibrosis Activation of Ca2+
-regulated Cl– channels Restoring CFTR function 4-phenylbutyrate S-nitrosoglutathione Xanthines Genistein Other agents
1.6.2 Gene therapy
3.1 X-ray microanalysis
3.1.1 Preparation of cells in culture
3.1.2 Preparation of nasal epithelial cells
3.1.3 Analysis
3.2 Measurements of intracellular Cl-with MQAE fluorescence
3.2.1 Preparation of cells in culture
3.2.2 Preparation of nasal epithelial cells
3.2.3 Analysis
3.3 Immunocytochemistry staining of CFTR
4.1 Measurements of chloride efflux (IV)
4.2 Activation of Cl transport in a airway epithelial cell lines (I-III)
4.2.1 Genistein and PBA (I, II)
4.2.2 GSNO (III)………………

Source: Uppsala University Library

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