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

Abstract

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 (750mJ/cm 2 ) of UVB light (311-313nm) with peaks at 3 and 18 hours post irradiation. DER overall reduced AP-1:DNA binding in mock-treated and UVB treated skin at 3 and 18 hours after UVB treatment. The timing of modulation of production of AP-1 constituent proteins by western blot analysis was examined at 0hr (mock treatment), 3hr, 9hr, 18hr, and 24hr. We found that c-jun (9 hr), jun-B (9 and 18hrs), phosphorylated c-jun (3hr), and fra-1 (18hr) 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 weeks 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 18hr. In addition, DER enhanced UVB-induced increase in jun-B levels and lowered basal levels of c-fos seen 18 hours 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.

Inhibitory effects of UV-based therapy on dry skin-inducible nerve growth in acetone-treated mice

“…A recent study demonstrated that 311-313 nm UVB radiation (dose: 750 mJ/cm 2 ) induced AP-1 binding to DNA [42]. These findings suggest that NB-UVB has the potential to modulate the expression of NGF in keratinocytes.…”

Energy Balance Modulates Mouse Skin Tumor Promotion through Altered IGF-1R and EGFR Crosstalk

“…Thus, a number of changes similar to those seen in our current study have been observed in skin/epidermis of obese mice (either diet-induced or genetically-induced obesity) following exposure to UVB. In a study by Hopper et al (51), CR was reported to inhibit UVB-induced upregulation of AP-1:DNA binding and UVB-induced alteration in AP-1 constituent protein levels suggesting that CR inhibited events associated with UVB-mediated skin tumor promotion. Only limited information is available on the potential link between dietary energy balance and non-melanoma skin cancer (NMSC) in humans (reviewed in 52), however, stronger evidence points to a relationship between obesity and melanoma skin cancer (reviewed in 52).…”

Cancer as a Metabolic Disease

“…It is well documented that dietary energy restriction can reduce the incidence of both inherited and acquired cancers in experimental animals [256,258,[306][307][308][309]. Evidence also indicates that dietary energy restriction can reduce the incidence of several human cancers [310,311].…”