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  • The EMBO Journal (2000) 19, 5793 - 5800
  • doi:10.1093/emboj/19.21.5793

Non-enzymatic triggering of the ceramide signalling cascade by solar UVA radiation

Susanne Grether-Beck1, Giuseppina Bonizzi2, Heidi Schmitt-Brenden1, Ingo Felsner1, Andreas Timmer1, Helmut Sies3,4, Judith P. Johnson5, Jacques Piette2 and Jean Krutmann1,4

  1. Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University, Moorenstras zlige 5, D-40225 Düsseldorf, Germany
  2. Laboratory of Virology and Immunology, Institute of Pathology, CHU B35, Sart-Tilman, University of Liege, 4000 Liege, Belgium
  3. Institute of Physiological Chemistry I, Heinrich-Heine-University, Universitätsstras zlige 1, D-40225 Düsseldorf, Germany
  4. Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-University, Universitätsstras zlige 1, D-40225 Düsseldorf, Germany
  5. Institute of Immunology, University of Munich, Goethestras zlige 31, D-8000 Munich 2, Germany

Correspondence to:

Jean Krutmann, E-mail: krutmann@rz.uni-duesseldorf.de

Received 8 May 2000; Accepted 19 September 2000; Revised 14 September 2000

Ceramide is a key component of intracellular stress responses. Evidence is provided for a novel mechanism of ceramide formation that mediates solar ultraviolet (UV) A radiation-induced expression of the intercellular adhesion molecule (ICAM)-1. Similarly to UVA radiation, ceramide stimulation of human keratinocytes induced ICAM-1 mRNA expression and activated the ICAM-1 promoter through transcription factor AP-2. Ceramide-activated AP-2 and ceramide-induced ICAM-1 reporter gene activation were abrogated through deletion of the AP-2 binding site. UVA radiation increased the level of ceramide in keratinocytes and inhibition of sphingomyelin synthesis prevented UVA radiation-induced ICAM-1 expression. Hitherto, two pathways have been identified for ceramide accumulation: hydrolysis from sphingomyelin through neutral and acid sphingomyelinases, and de novo synthesis by ceramide synthase. UVA radiation did not activate any of these enzymes. Ceramide generation in UVA-irradiated cells, however, was inhibited by singlet oxygen quenchers and mimicked in unirradiated cells by a singlet oxygen-generating system. In addition, UVA radiation and singlet oxygen both generated ceramide in protein-free, sphingomyelin-containing liposomes. This study indicates that singlet oxygen triggers a third, non-enzymatic mechanism of ceramide formation.

  • Keywords:

    • ceramide,
    • human keratinocytes,
    • signal transduction,
    • singlet oxygen,
    • ultraviolet radiation