Suppression of CFTR-mediated Cl- secretion of airway epithelium in vitamin C-deficient mice

Yeryung Kim, Hyemin Kim, Hae Young Yoo, Jae Seung Kang, Sung Joon Kim, Jin Kyoung Kim, Hyun Sung Cho

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (Isc) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloridesensitive Na+ absorption (ΔIsc,amil), cAMP-dependent Cl- secretion (ΔIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (ΔIsc,ATP). In mice exposed to 98% PO2 for 36 hr, ΔIsc,forsk decreased, ΔIsc,amil and ΔIsc,ATP was not affected. In gulo(-/-) mice, both ΔIsc,forsk and ΔIsc,ATP decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K+ channel was preserved. Taken together, the CFTR-mediated Cl- secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid.

Original languageEnglish
Pages (from-to)317-324
Number of pages8
JournalJournal of Korean Medical Science
Volume26
Issue number3
DOIs
StatePublished - 1 Mar 2011

Keywords

  • Airway epithelium
  • Ascorbic acid
  • Cystic fibrosis transmembrane conductance regulator
  • Electrolyte transport
  • Hyperoxia

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