Modulation of activator protein 1 (AP-1) constituent protein levels by dietary energy restriction (DER) before and after exposure to ultraviolet B (UVB) radiation in SKH-1 mice

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2005-01-01
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The study reported here examined the timing of modulation of the production of activator protein 1 (AP-1) constituent proteins by ultraviolet B (UVB) radiation and the effect of dietary energy restriction (DER, 40% reduction in calories from fat and carbohydrate compared to control diet) on these proteins in SKH-1 mouse epidermis using western blot analysis and electromobility shift assay (EMSA). The timing of modulation of the production of these proteins was examined at 0 hr (mock treatment), 3 hr, 9 hr, 18 hr, and 24 hr after treatment with a tumor promoting suberythemal dose (750mJ/cm2) of UVB light (311-313nm). We found that c-jun (9 hrs), jun-B (9 and 18 hrs), fra-1 (18 hrs), and phosphorylated c-jun (3 hrs) levels were increased after UVB treatment compared to mock controls. AP-1:DNA binding was also increased in a biphasic manner after UVB treatment with peaks at 3 and 18 hours post irradiation. In a second experiment, animals were placed on DER or control diet and treated with UVB as before. DER was found to completely block the UVB induced increase in phosphorylated c jun levels and decrease in fra-2 levels at 18 hrs. In addition, DER enhanced the UVB induced increase in jun B and lowered basal levels of c fos seen 18 hours after UVB. DER reduced basal levels of AP-1:DNA binding in both control fed and DER mice 3 hours after UVB treatment. These data suggest that DER may be able to assist in the prevention of UVB induced skin carcinogenesis by modulating AP-1 constituent protein levels and AP-1:DNA binding.

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Sat Jan 01 00:00:00 UTC 2005