Oxidative stress mediates synthesis of cytosolic phospholipase A2 after UVB injury.
UVB irradiation has previously been shown to significantly increase phospholipase activity and prostaglandin synthesis. Because UVB irradiation is a potent oxidative stress, the role of active oxygen species in regulating UV-induced cPLA2 synthesis and phosphorylation was examined. In the present study, irradiation produced a 3-fold increase in synthesis within 6 h following irradiation. Phosphorylation of cPLA2 was also increased to a similar extent. UVB-induced synthesis and phosphorylation of cPLA2 could be inhibited by pretreatment with the antioxidants 2,2,5,7,8-pentamethyl-6-hydroxychromane (50 microM) or N-acetylcysteine (10 mM). Treatment of unirradiated cultures with the potent oxidant tert-butyl hydroperoxide (500 microM) also increased cPLA2 synthesis and phosphorylation, suggesting that oxidative injury is an important regulator of cPLA2 synthesis. Increased synthesis of cPLA2 correlated well with increased [3H]arachidonic acid release, PGE2 synthesis and lipid peroxidation in epidermis after oxidant or UVB treatment. The results indicate that UVB-induced upregulation of cPLA2 synthesis is mediated by UVB-induced formation of free radicals.
Chen
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Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gresham
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Morrison
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Pentland
A P
AP
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D010545:Peroxides / Q000494:pharmacology; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D010766:Phosphorylation; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays; D020122:tert-Butylhydroperoxide
D000975:Antioxidants; D010545:Peroxides; D016718:Arachidonic Acid; D020122:tert-Butylhydroperoxide; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D000111:Acetylcysteine