Abstract
Abstract UV radiation is an important environmental factor in the pathogenesis of skin aging and cancer. Exposure of mammalian skin to UV results in oxidative damage, caused by increased cellular levels of reactive oxygen species (ROS). These include DNA breaks, protein inactivation, altered gene expression, loss of membrane lipid-bound essential polyunsaturated fatty acids and apoptosis. Omega-3 fatty acids, which occur at high levels in some fish oils, are known to have ROS scavenging activity and exert protective effects against photoaging and cancer. Their chemopreventive effects against UV-induced carcinogenesis are thought to be mediated through induction of antioxidant / phase 2 detoxifying enzymes, which are involved in elimination of ROS. In our present study, docosahexaenoic acid (DHA), a representative ω-3 fatty acid, significantly up-regulated the expression of two representative antioxidant enzymes, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase (NQO1) in a time-dependent manner with maximal induction observed at 12 hr and 24 hr, respectively in mouse epidermal JB6 cells. Nuclear factor E2-related factor 2 is a principal transcription factor that plays a pivotal role in the induction of many genes encoding antioxidant and other cytoprotective proteins. DHA (50 μM) treatment enhanced nuclear translocation of Nrf2 and its subsequent binding to antioxidant response element (ARE). DHA treatment increased the activity of mouse HO-1 promoter in JB6 cells as as assessed by the luciferase reporter assay. siRNA knock down of Nrf2 abrogated DHA-induced expression of HO-1 and NQO1. Moreover, DHA pretreatment significantly suppressed intracellular ROS formation in response to UVB. Over expression of HO-1 vector in JB6 cell abolished the ROS generation induced by UVB. These findings, taken together, suggest that DHA exerts protective effects against UVB-induced oxidative stress in mouse epidermal cells through Nrf2-induced expression of HO-1 and NQO1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5663.
Published Version
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