Solar simulated irradiation modulates gene expression and activity of antioxidant enzymes in cultured human dermal fibroblasts

Exposure of skin to solar irradiation generates reactive oxygen species tha t damage DNA, membranes. mitochondria and proteins. To protect against such damage, skin cells have evolved antioxidant enzymes including glutathione peroxidase (GSH-Px), copper and zinc-dependent superoxide dismutase (SOD1), the mitochondrial manganese-dependent superoxide dismutase (SOD2), and cat alase. This report examines the effect of a single low or moderate dose exp osure to solar-simulating combined UVB and UVA irradiation on the gene expr ession and activities of these antioxidant enzymes in cultured normal human fibroblasts. We find that both doses initially decrease GSH-Px, SOD2 and c atalase activities, but within 5 days after irradiation the activities of t he enzymes return to pre-irradiation level (catalase) or are induced slight ly (SOD1, GSH-Px) or substantially (SOD2) above the basal level. For SOD1, SOD2 and catalase, the higher dose also detectably modulates the mRNA level of these enzymes. Our results indicate that the effects of a single physio logic solar simulated irradiation dose persist for at least several days an d suggest that skin cells prepare for subsequent exposure to damaging irrad iation by upregulating this antioxidant defense system, in particular the m itochondrial SOD2. Our findings are consistent with the existence of a broa d-based SOS-like response in irradiated human skin.