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 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 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 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.
Djavaheri-Mergny
M
M
Laboratoire de Physico-Chimie de l'Adaptation Biologique, INSERM U312, Muséum National d'Histoire Naturelle de Paris, France.
Mazière
C
C
Santus
R
R
Dubertret
L
L
Mazière
J C
JC
D000975:Antioxidants / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002460:Cell Line; D004075:Diglycerides / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D004075:Diglycerides; D014810:Vitamin E; D004815:Epidermal Growth Factor; D010738:Type C Phospholipases