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

Susanne Grether-Beck, Giuseppina Bonizzi, Heidi Schmitt-Brenden, Ingo Felsner, Andreas Timmer, Helmut Sies, Judith P. Johnson, Jacques Piette, Jean Krutmann

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)5793-5800
Number of pages8
JournalEMBO Journal
Volume19
Issue number21
Publication statusPublished - Nov 1 2000

Keywords

  • Ceramide
  • Human keratinocytes
  • Signal transduction
  • Singlet oxygen
  • Ultraviolet radiation

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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