Adaptive antioxidant response protects dermal fibroblasts from UVA-inducedphototoxicity

In response to the attack, of reactive oxygen species (ROS) produced upon U V irradiation, the skin has developed a complex antioxidant defense system. Hen we report that, in addition to the previously published induction of m anganese superoxide dismutase (MnSOD) activity, single and, to a higher ext ent, repetitive low-dose UVA irradiation also leads to a substantial upregu lation of glutathione peroxidase (GPx) activity. This concomitant adaptive response of two antioxidant enzymes acting in the same detoxification pathw ay coincided with the protection from high-UVA-dose-induced cytotoxicity co nferred by low-dose UVA preirradiation. Whereas an interval of 24 h did not , an interval of 12 h did lead to the induction of MnSOD activity and, unde r selenium-supplemented conditions. of GPx activity as well, conferring def inite cellular protection from UVA-induced phototoxicity. Moreover, under s elenium-deficient conditions, which abrogate the UVA-mediated induction of GPx activity, adaptive protection against the cytotoxic effects of high WA doses was significantly lower compared with selenium supplementation. Isola ted 4.6-fold overexpression of MnSOD activity in stably transfected fibrobl asts led to specific resistance from UVA-mediated phototoxicity under selen ium-deficient conditions. Collectively, these data indicate that the concom itant induction of MnSOD and GPx activity is related to the optimal adaptiv e protection from photooxidative damage. This adaptive antioxidant protecti on clearly depends on the irradiation interval and a sufficient selenium co ncentration, findings that may have important implications for the improvem ent of photoprotective and phototherapeutic strategics in medicine. (C) 200 1 Elsevier Science Inc.