ULTRAVIOLET A DECREASES EPIDERMAL GROWTH-FACTOR (EGF) PROCESSING IN CULTURED HUMAN FIBROBLASTS AND KERATINOCYTES - INHIBITION OF EGF-INDUCED DIACYLGLYCEROL FORMATION

The binding, uptake, and degradation of epidermal growth factor (EGF) has been studied in MRCS human fibroblasts and NCTC 2544 human keratinocytes following ultraviolet A (UVA) irradiation at doses up to 18.9 J/cm(2), which are not lethal to cells under our experimental conditions. A dose-dependent reduction in EGF binding was observed, with an approximately 75% decrease at the maximal studied UVA dose. At lower doses (6 to 12 J/cm(2)), EGF binding was more affected by ultraviolet A in fibroblasts than in keratinocytes. In both cell types, this effect of UVA appeared to be related to a reduction of the affinity of the EGF receptor for EGF. Kinetic studies by pulse-chase experiments indicated that EGF is more rapidly internalized by keratinocytes than by fibroblasts, and that UVA exposure resulted in a slower decay of EGF intracellular content. A 24-h pretreatment of cells with 5 X 10(-5) M vitamin E strongly reduced the appearance of light-induced lipid peroxidation products measured via assay of thiobarbituric acid reactive substances formation, but only partially prevented the UVA-induced alterations of EGF processing by cells. Finally, UVA exposure almost completely abolished the EGF-induced increase in diacylglycerol production from C-14-arachidonic acid-labeled lipids in both cell types. These results demonstrate that UVA radiation induces important changes in EGF processing and could participate in the light-induced degenerative processes of the skin.