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 keratin ocytes following ultraviolet A (UVA) irradiation at doses up to 18.9 J /cm(2), which are not lethal to cells under our experimental condition s. A dose-dependent reduction in EGF binding was observed, with an app roximately 75% decrease at the maximal studied UVA dose. At lower dose s (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 fibrob lasts, and that UVA exposure resulted in a slower decay of EGF intrace llular 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 substance s formation, but only partially prevented the UVA-induced alterations of EGF processing by cells. Finally, UVA exposure almost completely ab olished the EGF-induced increase in diacylglycerol production from C-1 4-arachidonic acid-labeled lipids in both cell types. These results de monstrate that UVA radiation induces important changes in EGF processi ng and could participate in the light-induced degenerative processes o f the skin.