Non-enzymatic triggering of the ceramide signalling cascade by solar UVA radiation.
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.
Grether-Beck
S
S
Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University, Moorenstrabetae 5, D-40225 Düsseldorf, Germany.
Bonizzi
G
G
Schmitt-Brenden
H
H
Felsner
I
I
Timmer
A
A
Sies
H
H
Johnson
J P
JP
Piette
J
J
Krutmann
J
J
D001483:Base Sequence; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism* / Q000528:radiation effects*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000528:radiation effects; D026082:Singlet Oxygen; D013109:Sphingomyelins / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism; D014466:Ultraviolet Rays
D002518:Ceramides; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D013109:Sphingomyelins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D018799:Intercellular Adhesion Molecule-1; D026082:Singlet Oxygen; D010100:Oxygen