UVB radiation affects the mobility of epidermal growth factor receptors in human keratinocytes and fibroblasts

Abstract

Growth factor receptors transmit biological signals for the stimulation of cell growth in vitro and in vivo and their autocrine stimulation may be involved in tumorigenesis. It is therefore, of great value to understand receptor reactions in response to ultraviolet (UV) light which certain normal human cells are invaribly exposed to during their growth cycle. UV irradiation has recently been shown to deplete antioxidant enzymes in human skin. The aims of the present study were a) to compare the lateral mobility of epidermal growth factor receptors (EGF-R) in cultured human keratinocytes and human foreskin fibroblasts, b) to investigate effects of ultraviolet B radiation on the mobility of EGF-R in these cells, and c) study the response of EGF-R on addition of antioxidant enzymes. The epidermal growth factor receptors were labeled with rhodaminated EGF, the lateral diffusion was determined and the fraction of mobile EGF-R assessed with the fluorescence recovery after photobleaching (FRAP). We found that human keratinocytes display a higher basal level of EGF-R mobility than human skin fibroblasts, viz. with diffusion coefficients (D +/- standard error of the mean, SEM) of 4.2 +/- 0.2 x 10(-10) cm2/s, and 1.8 +/- 0.2 x 10(-10) cm2/s, respectively. UVB-irradiated fibroblasts showed an almost four-fold increase in the diffusion coefficient; D was 6.3 +/- 0.3 x 10(-10) cm2/s. The keratinocytes, however, displayed no significant increase in receptor diffusion after irradiation; D was 5.1 +/- 0.8 x 10(-10) cm2/s. In both cell types the percentage of EGF-R fluorescence recovery after photobleaching, i.e. the fraction of mobile receptors, was significantly increased after irradiation. In keratinocytes it increased from 69% before irradiation to 78% after irradiation. Analogous figures for fibroblasts were 61% and 73%. The effect of UVB on fibroblast receptors was abolished by prior addition of superoxide dismutase (SOD) and catalase (CAT). It is concluded that UVB radiation of fibroblasts and keratinocytes can affect their biophysical properties of EGF-R. The finding that addition of antioxidant enzymes prevented the UVB effect in fibroblasts may indicate the involvement of reactive oxygen metabolites.

Cutaneous epidermal growth factor receptor system following ultraviolet irradiation: exploring the role of molecular mechanisms

“…Discrepancies in selection were evaluated by agreement between both investigators. Full manuscripts were retrieved for 32 citations (9–40). The findings and results of the selected full articles are later outlined successively.…”

“…The effect of UVB on fibroblast receptors is abolished by the prior addition of superoxide dismutase and catalase, concluding that UVB radiation of fibroblasts and keratinocytes can thus affect the biophysical properties of EGFR. The discovery that the addition of antioxidant enzymes prevented the UVB effect in fibroblasts may indicate the involvement of ROS (18).…”

Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging

“…Hyaluronate, a mucopolysaccharide involved in the maintenance of dermal volume and elasticity, is decreased in aged skin 8 . This can be explained by the reduction of epidermal growth factor receptor expression following UV exposure 27,28 and subsequent inhibition of hyaluronate synthesis 29,30 …”