文章基本信息

标题：Vitamin C controls the cystic fibrosis transmembrane conductance regulator chloride channel
本地全文：下载
作者：Horst Fischer ; Christian Schwarzer ; Beate Illek 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：10
页码：3691-3696
DOI：10.1073/pnas.0308393100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Vitamin C (L-ascorbate) is present in the respiratory lining fluid of human lungs, and local deficits occur during oxidative stress. Here we report a unique function of vitamin C on the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), a cAMP-dependent Cl channel that regulates epithelial surface fluid secretion. Vitamin C (100 {micro}M) induced the openings of CFTR Cl channels by increasing its average open probability from 0 to 0.21 {+/-} 0.08, without a detectable increase in intracellular cAMP levels. Exposure of the apical airway surface to vitamin C stimulated the transepithelial Cl secretion to 68% of forskolin-stimulated currents. The average half-maximal stimulatory constant was 36.5 {+/-} 2.9 {micro}M, which corresponds to physiological concentrations. When vitamin C was instilled into the nasal epithelium of human subjects, it effectively activated Cl transport in vivo. In CF epithelia, previous treatment of the underlying trafficking defect with trimethylamine oxide or expression of WT CFTR restored the activation of Cl transport by vitamin C. Sodium dependency and phloretin sensitivity, as well as the expression of transcripts for sodium-dependent vitamin C transporter (SVCT)-1 and SVCT2, support a model in which an apical vitamin C transporter is central for relaying the effect of vitamin C to CFTR. We conclude that cellular vitamin C is a biological regulator of CFTR-mediated Cl secretion in epithelia. The pool of vitamin C in the respiratory tract represents a potential nutraceutical and pharmaceutical target for the complementary treatment of sticky airway secretions by enhancing epithelial fluid secretion.
关键词：ascorbate ; Cl channel opener ; epithelia ; ΔF508 CFTR ; airway disease