UVA radiation stimulates ceramide production: Relationship to oxidative stress and potential role in ERK, JNK, and p38 activation

Exposure of human keratinocytes to WA radiation induced an increase in cera mide (CER) intracellular content, with a dose-dependent effect within the r ange of 4-9 J/cm(2), The production of CER reached a maximum 2 h after WA i rradiation, The increase of CER was proportional to the intracellular conte nt of reactive oxygen species, was prevented by the antioxidant vitamin E, and enhanced by the prooxidant buthionine-sulfoximine, suggesting the invol vement of an oxidative stress. WA decreased both neutral and acid sghingomy elinase activities measured in vitro, A direct cleavage of sphingomyelin to CER by WA, recently described, was not observed under our experimental con ditions. We also show that, downstream of CER, WA activated the Ser/Thr kin ases ERK, JNK, and p38, Since ceramide has been shown to play a role in str ess kinase activation, our results provide a possible mechanism for WA-indu ced activation of stress kinases via ceramide formation. However, the actua l mechanisms whereby CER is produced in cultured cells under WA exposure re main to be specified, (C) 2001 Academic Prees.