Regulation of Cu,Zn‐superoxide dismutase in bovine pulmonary artery endothelial cells

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Abstract
To evaluate the regulation of endothelial cell Cu,Zn-SOD, we have exposed bovine pulmonary artery endothelial cells in culture to hyperoxia and hypoxia, second messengers or related agonists, hormones, free radical generating systems, endotoxin, and cytokines and have measured Cu,Zn-SOD protein of these cells by an ELISA developed in our laboratory. Control preconfluent and confluent cells in room air contained 196 ± 18 ng Cu,Zn-SOD/106 cells. A23187 (0.33 μM), for skolin (10 μM), isobutylmethylxanthine (0.1 mM), dexamethasone (1 μM), triiodothyronine (1 μM) and retinoic acid (1 μM) failed to alter this level of Cu,Zn-SOD. Exposure to anoxia and hyperoxia both elevated the level −1.5–2.0-fold over 20% oxygen-exposed controls at 48–72 hr. Similarly, exposures to glucose oxidase (0.0075 units/ml), menadione (12.5 μM), xanthine-xanthine oxidase (10 μM, 0.03 units/ml) and H2O2 (0.0005%) increased the level up to two–threefold over controls at 24–48 hr. Lipopolysaccharide, TGFβ1, TNFα, and II-1 also increased levels of cellular Cu,Zn-SOD, but only in proliferating cells. II-2, II-4, interferon-γ, and GM-CSF had no effect on Cu,Zn-SOD. All treatments that elevated SOD resulted in inhibition of cellular growth, but decreased growth of cells at confluence alone was not associated with increased Cu,Zn-SOD. We propose from these studies that Cu,Zn-SOD of endothelial cells is not under conventional second messenger or hormonal regulation, but that up-regulation of the enzyme is associated with (and perhaps stimulated by) free-radical or oxidant production that also may be influenced by availability of certain cytokines under replicating conditions.

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