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The effect of S-nitrosoglutathione and L-cysteine on chloride efflux from cystic fibrosis airway epithelial cells
- Source :
- Experimental and molecular pathology. 90(1)
- Publication Year :
- 2010
-
Abstract
- The endogenous bronchodilator, S-nitrosoglutathione (GSNO), has been proposed as a possible pharmacological remedy that reverses the ΔF508-CFTR (cystic fibrosis transmembrane conductance regulator) maturation defect and increases CFTR-mediated chloride efflux in cultured cystic fibrosis airway epithelial cells (CFBE41o(-)). It has also been reported that L-cysteine enhanced S-nitrosothiol uptake and increased the intracellular S-nitrosothiol levels, likely through transnitrosation chemistry. The present study investigated whether L-cysteine augmented the effect of GSNO on chloride efflux from CF airway epithelial cells. Treatment with 10 μM GSNO combined with 20 μM L-cysteine resulted in increased chloride efflux from CFBE41o(-) cells after 5 minutes exposure compared to the control efflux rate and to the efflux rate in the presence of L-cysteine alone as measured using the fluorescent dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE). Chloride efflux rates from these cells after 4h exposure to GSNO and L-cysteine were not different from control. Treatment with 10 μM GSNO alone increased chloride efflux from CFBE41o(-) cells after 4h but not at shorter incubation times. GSNO with or without L-cysteine did not alter epithelial tight junction integrity. In conclusion, a combination of GSNO with L-cysteine led to significant increase in chloride efflux in CFBE41o(-) cells but the effect was transient and not sustained beyond minutes.
- Subjects :
- congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
Time Factors
Cystic Fibrosis
Clinical Biochemistry
Endogeny
Respiratory Mucosa
Pharmacology
Cystic fibrosis
Pathology and Forensic Medicine
Cell Line
S-Nitrosoglutathione
chemistry.chemical_compound
Chlorides
Internal medicine
medicine
Humans
Cysteine
Molecular Biology
Cysteine metabolism
Transepithelial potential difference
business.industry
Drug Synergism
respiratory system
medicine.disease
digestive system diseases
Transmembrane protein
respiratory tract diseases
Bronchodilator Agents
Endocrinology
chemistry
Efflux
business
Subjects
Details
- ISSN :
- 10960945
- Volume :
- 90
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Experimental and molecular pathology
- Accession number :
- edsair.doi.dedup.....74b16b7de9d9ed604e2c9e6824492fea