Oxidative stress mediates synthesis of cytosolic phospholipase A2 after UVB injury

Abstract

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.