Possible role of ROS as mediators of hypoxia-induced ion transport inhibition of alveolar epithelial cells.
In oxygen-sensitive excitable cells, responses to hypoxia are initiated by membrane depolarization due to closing of the K channels that is thought to be mediated by a decrease in reactive oxygen species (ROS). Because the mechanisms of hypoxic inhibition of ion transport of alveolar epithelial cells (Planes C, Friedlander G, Loiseau A, Amiel C, and Clerici C. Am J Physiol Lung Cell Mol Physiol 271: L70-L78, 1996; Mairbäurl H, Wodopia R, Eckes S, Schulz S, and Bärtsch P. Am J Physiol Lung Cell Mol Physiol 273: L797-L806, 1997) are not yet understood, we tested the possible involvement of a hypoxia-induced change in ROS that might control transport activity. Transport was measured as (86)Rb and (22)Na uptake in A549 cells exposed to normoxia, hyperoxia, or hypoxia together with ROS donors and scavengers. H(2)O(2) < 1 mM did not affect transport, whereas 1 mM H(2)O(2) activated (22)Na uptake (+200%) but inhibited (86)Rb uptake (-30%). Also hyperoxia, aminotriazole plus menadione, and diethyldithiocarbamate inhibited (86)Rb uptake. N-acetyl-L-cysteine, diphenyleneiodonium, and tetramethylpiperidine-N-oxyl, used to reduce ROS, inhibited (86)Rb uptake, thus mimicking the hypoxic effects, whereas deferoxamine, superoxide dismutase, and catalase were ineffective. Also, hypoxic effects on ion transport were not prevented in the presence of H(2)O(2), diethyldithiocarbamate, and N-acetyl-L-cysteine. These results indicate that ion transport of A549 cells is significantly affected by decreasing or increasing cellular ROS levels and that it is possible that certain species of ROS might mediate the hypoxic effects on ion transport of alveolar epithelial cells.
Heberlein
W
W
Department of Sports Medicine, Medical Clinic, University of Heidelberg, 69115 Heidelberg, Germany.
Wodopia
R
R
Bärtsch
P
P
Mairbäurl
H
H
D000111:Acetylcysteine / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018496:Hyperoxia / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D007477:Ions; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000502:physiology*; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D016166:Free Radical Scavengers; D007477:Ions; D016877:Oxidants; D017382:Reactive Oxygen Species; D012964:Sodium; D006861:Hydrogen Peroxide; D012413:Rubidium; D000111:Acetylcysteine