Ultraviolet A Decreases Epidermal Growth Factor (EGF) Processing in Cultured Human Fibroblasts and Keratinocytes: Inhibition of EGF-Induced Diacylglycerol Formation

• Published in: Journal of investigative dermatology Vol. 102; no. 2; pp. 192 - 196
• Main Authors: Djavaheri-Mergny, M., Mazière, C., Santus, R., Dubertret, L., Mazière, J.C.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Danvers, MA Elsevier Inc 01-02-1994; Nature Publishing
• Subjects: Antioxidants - pharmacology; Arachidonic Acids - pharmacology; Biological and medical sciences; Carbon Radioisotopes; Cell Line; diacylglycerol; Diglycerides - metabolism; Dose-Response Relationship, Radiation; Enzyme Activation; epidermal growth factor (EGF); Epidermal Growth Factor - metabolism; Epidermal Growth Factor - physiology; Fibroblasts - cytology; Fibroblasts - metabolism; Fibroblasts - radiation effects; Fundamental and applied biological sciences. Psychology; human fibroblasts; human keratinocytes; Humans; Keratinocytes - cytology; Keratinocytes - metabolism; Keratinocytes - radiation effects; Time Factors; Type C Phospholipases - metabolism; ultraviolet A (UVA); Ultraviolet Rays; Vertebrates: skin, associated glands, phaneres, light organs, various exocrine glands (salt gland, uropygial gland...), adipose tissue, connective tissue; Vitamin E - pharmacology; epidermal growth factor (EGF); human keratinocytes; human fibroblasts; diacylglycerol; ultraviolet A (UVA); Human; Cell culture; UVA radiation; Diglyceride; Cytokine; Experimental study; Metabolism; Epidermal growth factor; Ultraviolet irradiation; Polypeptide; Keratinocyte; Skin; Fibroblast; Comparative study; Growth factor; Biological receptor
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/1523-1747.ep12371761

The binding, uptake, and degradation of epidermal growth factor (EGF) has been studied in MRC5 human fibroblasts and NCTC 2544 human keratinocytes following ultraviolet A (UVA) irradiation at doses up to 18.9 J/cm2, 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/cm2), 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 × 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 14C-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.