1. ¹Zellbiologie, Institut fuer Umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University Duesseldorf gGmbH, Duesseldorf, Germany
2. ²Internal Medicine IV, University of Heidelberg, Heidelberg, Germany

Correspondence: Dr S Grether-Beck, Zellbiologie, Institut fuer Umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University Duesseldorf gGmbH, Auf'm Hennekamp 50, Duesseldorf D-40225, Germany. E-mail: grether-beck@uni-duesseldorf.de

Received 6 September 2007; Revised 11 February 2008; Accepted 14 March 2008; Published online 28 April 2008.

Abstract

Solar ultraviolet A (UVA) (320–400 nm) radiation-induced gene expression in keratinocytes is initiated at the level of the cell membrane via generation of singlet oxygen and subsequent formation of ceramide from sphingomyelin. We now report that the UVA response also involves raft signaling and that ceramide and raft signaling are linked with each other. Upon UVA irradiation, the lipid composition of rafts decreased 40% in sphingomyelin and 60% in cholesterol (Chol). Also, decrease of Chol increased the susceptibility towards UVA-induced gene expression, whereas increase of Chol completely abolished their capacity to generate signaling ceramides and to mount the subsequent UVA response. This inhibition was not associated with UVA-induced Chol oxidation and was also seen after treatment of cells with plant sterols. The UVA responsiveness depended on the ratio of Chol versus ceramide in rafts. A ratio smaller than 1 permitted initiation and transduction of the signaling response, whereas a ratio greater than 1, for example, upon sterol pretreatment, abolished this response, indicating that UVA radiation-induced ceramide signaling is controlled by the lipid composition of rafts.