P. Pietarinenruntti et al., ANTIOXIDANT ENZYME REGULATION AND RESISTANCE TO OXIDANTS OF HUMAN BRONCHIAL EPITHELIAL-CELLS CULTURED UNDER HYPEROXIC CONDITIONS, American journal of respiratory cell and molecular biology, 19(2), 1998, pp. 286-292
Bronchial epithelial cells are the first cells to encounter high conce
ntrations of inspired oxygen, and their damage is a typical feature in
many airway diseases. The direct effect of oxygen on the expression o
f the main antioxidant enzymes (AOEs) in human bronchial epithelial ce
lls is unknown. We investigated the messenger RNA (mRNA) levels of man
ganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase
(CuZnSOD), catalase (CAT), and glutathione peroxidase (GPx), as well a
s the specific activities of MnSOD, CuZnSOD, CAT, GPx, and glutathione
reductase, in BEAS-2B bronchial epithelial cells exposed to hyperoxia
(95% O2, 5% CO2) for 16 to 48 h. We also assessed the resistance of c
ells preexposed to hyperoxia to subsequent oxidant stress. Significant
cell injury was observed after 72 h exposure to hyperoxia; release of
lactate dehydrogenase (LDH) from control cells and cells exposed to h
yperoxia for 72 h was 7.0 +/- 1.0% and 22.0 +/- 1.0%, respectively. Hy
peroxia for 16 h, 24 h, or 48 h had no effect on the mRNA levels or sp
ecific activities of any of these enzymes. Despite their unchanged AOE
levels, cells exposed to hyperoxia for 48 h showed increased resistan
ce to H2O2 and menadione. Total glutathione content of the cells incre
ased by 55% and 58% after 24 h and 38 h, respectively, compared with n
ormoxic controls. However, glutathione depletion with buthionine sulfo
ximine (BSO) did not diminish the oxidant resistance of hyperoxia-expo
sed cells. We conclude that AOEs in human bronchial epithelial cells a
re not directly upregulated by high oxygen tension, and that increases
in AOE-specific activities or glutathione are not necessary for the d
evelopment of increased oxidant resistance in these cells.