Sunburned by Ceramide

Abstract

Ultraviolet (UV) radiation causes a variety of pathogenic processes ranging from sunburn to skin cancer. UV radiation is known to alter gene expression, but the exact ways in which cells sense such radiation are not fully understood. Grether-Beck et al. show that long-wavelength UV radiation (UVA) stimulates the release of ceramide in keratinocytes and that this increase occurs without increased sphingomyelinase activity or stimulation of the de novo ceramide biosynthetic pathway. In liposomes of defined lipid composition completely lacking protein, the release of ceramide was stimulated by either UVA radiation or a singlet oxygen generator, 3,3'-(1,4-naphthylidene)dipropionate (NDPO 2 ), suggesting that oxygen free radicals may be responsible for the UVA-induced ceramide production. Consistent with this mechanism, the increase in ceramide in keratinocytes treated with NDPO 2 or UVA radiation can be inhibited by treatment of the cells with singlet oxygen quenchers. Finally, the physiological importance of ceramide production was demonstrated by treating the cells with exogenous ceramide and showing that this mimicked the increase in gene expression mediated by the AP-2 transcription factor seen in UV-irradiated cells. Grether-Beck, S., Bonizzi, G., Schmitt-Brenden, H., Felsner, I., Timmer, A., Sies, H., Johnson, J.P., Piette, J., and Krutmann, J. (2000) Non-enzymatic triggering of the ceramide signalling cascade by solar UVA radiation. EMBO J. 19 : 5793-5800. [Abstract] [Full Text]