Effect of ultraviolet B radiation on activator protein 1 constituent proteins and modulation by dietary energy restriction in SKH-1 mouse skin.
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/cm(2)) 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.
Hopper
Brian D
BD
Interdepartmental Toxicology Program, Iowa State University, Ames, Iowa 50011-1123, USA.
Przybyszewski
Joseph
J
Chen
Haw-Wen
HW
Hammer
Kimberly D P
KD
Birt
Diane F
DF
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D031204:Caloric Restriction; D004307:Dose-Response Relationship, Radiation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D011485:Protein Binding / Q000528:radiation effects; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014466:Ultraviolet Rays
D018808:Transcription Factor AP-1