Effect of ultraviolet B radiation on activator protein 1 constituent proteins and modulation by dietary energy restriction in SKH-1 mouse skin

• Published in: Molecular carcinogenesis Vol. 48; no. 9; pp. 843 - 852
• Main Authors: Hopper, Brian D., Przybyszewski, Joseph, Chen, Haw-Wen, Hammer, Kimberly D.P., Birt, Diane F.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-09-2009
• Subjects: activator protein 1; Analysis of Variance; Animals; Blotting, Western; Body Weight; Caloric Restriction; dietary energy restriction; Dose-Response Relationship, Radiation; Electrophoretic Mobility Shift Assay; Female; Mice; Mice, Hairless; mouse; Protein Binding - radiation effects; skin; Skin - metabolism; Skin - pathology; Skin - radiation effects; Transcription Factor AP-1 - metabolism; Ultraviolet Rays; UV light
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.20529

The study examined the timing of modulation of activator protein 1(AP‐1):DNA binding and production of AP‐1 constituent proteins by ultraviolet B (UVB) radiation and effect of dietary energy restriction [DER, 40% calorie reduction from fat and carbohydrate compared to control ad libitum (AL) diet] in SKH‐1 mouse epidermis. AP‐1:DNA binding by electromobility shift assay (EMSA) was increased in a biphasic manner after treatment with a tumor‐promoting suberythemal dose (750 mJ/cm2) of UVB light (311–313 nm) with peaks at 3 and 18 h postirradiation. DER overall reduced AP‐1:DNA binding in mock‐treated and UVB‐treated skin at 3 and 18 h after UVB treatment. The timing of modulation of production of AP‐1 constituent proteins by Western blot analysis was examined at 0 h (mock treatment), 3, 9, 18, and 24 h. We found that c‐jun (9 h), jun‐B (9 and 18 h), phosphorylated c‐jun (3 h), and fra‐1 (18 h) protein levels were increased after UVB treatment compared to mock controls. In a follow‐up diet experiment, animals were placed on DER or AL diet for 10–12 wk and treated with UVB as before. DER was found to completely block the UVB‐induced increase in phosphorylated c‐jun protein levels and decrease in fra‐2 protein levels at 18 h. In addition, DER enhanced UVB‐induced increase in jun B levels and lowered basal levels of c‐fos seen 18 h after UVB. These data suggest that DER may be able to assist in the prevention of UVB‐induced skin carcinogenesis by modulating AP‐1:DNA binding and AP‐1 constituent protein levels. © 2009 Wiley‐Liss, Inc.