OXIDATIVE STRESS MEDIATES SYNTHESIS OF CYTOSOLIC PHOSPHOLIPASE A(2) AFTER UVB INJURY

UVB irradiation has previously been shown to significantly increase ph ospholipase activity and prostaglandin synthesis. Because WB irradiati on is a potent oxidative stress, the role of active oxygen species in regulating UV-induced cPLA(2) synthesis and phosphorylation was examin ed. In the present study, irradiation produced a 3-fold increase in sy nthesis within 6 h following irradiation. Phosphorylation of cPLA(2) w as also increased to a similar extent. WE-induced synthesis and phosph orylation of cPLA(2) could be inhibited by pretreatment with the antio xidants 2,2,5,7,8-pentamethyl-6-hydroxychromane (50 mu M) or N-acetylc ysteine (10 mM). Treatment of unirradiated cultures with the potent ox idant tert-butyl hydroperoxide (500 mu M) also increased cPLA(2) synth esis and phosphorylation, suggesting that oxidative injury is an impor tant regulator of cPLA(2) synthesis. Increased synthesis of cPLA(2) co rrelated well with increased [H-3]arachidonic acid release, PGE(2) syn thesis and lipid peroxidation in epidermis after oxidant or UVB treatm ent. The results indicate that UVB-induced upregulation of cPLA(2) syn thesis is mediated by UVB-induced formation of free radicals.