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

✍ Scribed by Xue-Jun Kong; Barry L. Fanburg

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 738 KB
• Volume: 153
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041530308

✦ Synopsis

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 thew cells by an ELISA developed in our laboratory. Control preconfluent and confluent cells in room air contained 196 ? 18 ng Cu,Zn-SOD/lO' cells. A231 87 (0.33 pM), forskolin (10 pMj, isobutylmethylxanthine (0.1 mM), dexamcthasonc (1 pM), triiodothyronine (1 kM) and retinoic acid (1 pM) 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 (1 2.5 pM), xanthine-xanthine oxidase (10 pM, 0.03 unitsirnlj and H,O, (0.0005%) increased the level u p to two-threefold over controls at 2 4 4 8 hr. Lipopolysaccharide, TCF,,, TNF,, and 11-1 also increased levels of cellular Cu,Zn-SOU, but only in proliferating cells. 11-2, 11-4, interferon-y, and CM-CSF had n o effect o n 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-SOU. 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. 6 1992 WiIcy-Liss, Inc.