OP-30 - Protective Effects of fat-1 Gene against UVB-induced Oxidative Stress and Inflammation in Mouse Skin

Abstract

Omega-6 (ω-6) and omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are known to have opposite effects on the inflammation-associated carcinogenesis. Generally, ω-6 PUFAs promote inflammation and tumor development, whereas ω-3 PUFAs possess anti-inflammatory as well as antioxidative activity. In the present study, we investigated the protective capability of ω-3 PUFAs endogenously produced in fat-1 transgenic mice. The ω-3/ω-6 PUFA ratio was significantly higher in the dorsal skin of fat-1 mice than that in the wild-type (WT) C57BL/6 mice. In comparison to WT animals, elevated levels of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1, were found in the skin of fat-1 mice, which was attributable to the enhanced activation of nuclear factor erythroid-related factor-2 (Nrf2). Upon single exposure to UVB (5.0 kJ/m2) radiation, fat­-1 mice showed a markedly reduced degree of skin inflammation and expression of pro-inflammatory enzymes, cyclooxygenases-2 and inducible nitric oxide synthase, compared with the WT animals. The protection of fat-1 mice from UVB-induced phototoxicity was associated with decreased phosphorylation of STAT3. In conclusion, our results show that fat-1 gene confers a protective effect against UVB-induced inflammatory and oxidative skin damages through augmented endogenous ω-3 PUFA production.