Suppression of CFTR-mediated Cl- Secretion of Airway Epithelium in Vitamin C-deficient Mice.
10.3346/jkms.2011.26.3.317
- Author:
Yeryung KIM
1
;
Hyemin KIM
;
Hae Young YOO
;
Jae Seung KANG
;
Sung Joon KIM
;
Jin Kyoung KIM
;
Hyun Sung CHO
Author Information
1. Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. jkane.kim@samsung.com
- Publication Type:Original Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
- Keywords:
Hyperoxia;
Airway Epithelium;
Cystic Fibrosis Transmembrane Conductance Regulator;
Electrolyte Transport;
Ascorbic Acid
- MeSH:
Animals;
Ascorbic Acid Deficiency/*metabolism;
Biological Transport/drug effects;
Chlorides/*metabolism;
Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & inhibitors/drug;
Forskolin/pharmacology;
Hyperbaric Oxygenation;
Hyperoxia/*physiopathology;
Ion Transport/drug effects;
Mice;
Mice, Inbred C57BL;
Mice, Inbred ICR;
Mice, Knockout/metabolism;
Mice, Transgenic;
Microscopy, Fluorescence;
Oxidative Stress;
Oxygen/adverse effects/pharmacology;
Potassium Channels/metabolism;
Respiratory Mucosa/drug effects/*metabolism/secretion;
Sodium;
Sugar Acids/metabolism
- From:Journal of Korean Medical Science
2011;26(3):317-324
- CountryRepublic of Korea
- Language:English
-
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 amiloride-sensitive Na+ absorption (DeltaIsc,amil), cAMP-dependent Cl- secretion (DeltaIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (DeltaIsc,ATP). In mice exposed to 98% PO2 for 36 hr, DeltaIsc,forsk decreased, DeltaIsc,amil and DeltaIsc,ATP was not affected. In gulo(-/-) mice, both DeltaIsc,forsk and DeltaIsc,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.
