Oxidative stress mediates synthesis of cytosolic phospholipase A(2) after UVB injury

UVB irradiation has previously been shown to significantly increase phospholipase activity and prostaglandin synthesis. Because WB irradiation is a potent oxidative stress, the role of active oxygen species in regulating UV-induced cPLA(2) synthesis and phosphorylation was examined. In the present study, irradiation produced a 3-fold increase in synthesis within 6 h following irradiation. Phosphorylation of cPLA(2) was also increased to a similar extent. WE-induced synthesis and phosphorylation of cPLA(2) could be inhibited by pretreatment with the antioxidants 2,2,5,7,8-pentamethyl-6-hydroxychromane (50 mu M) or N-acetylcysteine (10 mM). Treatment of unirradiated cultures with the potent oxidant tert-butyl hydroperoxide (500 mu M) also increased cPLA(2) synthesis and phosphorylation, suggesting that oxidative injury is an important regulator of cPLA(2) synthesis. Increased synthesis of cPLA(2) correlated well with increased [H-3]arachidonic acid release, PGE(2) synthesis and lipid peroxidation in epidermis after oxidant or UVB treatment. The results indicate that UVB-induced upregulation of cPLA(2) synthesis is mediated by UVB-induced formation of free radicals.