Ultraviolet A-induced signaling involves a ceramide-mediated autocrine loop leading to ceramide de novo synthesis.
J Invest Dermatol
; 125(3): 545-53, 2005 Sep.
Article
em En
| MEDLINE
| ID: mdl-16117797
ABSTRACT
Exposure of human keratinocytes to ultraviolet A (UVA) radiation at physiological doses leads to a biphasic activation of transcription factor activator protein-2 (AP-2) and subsequently to a biphasic increase in gene expression of, e.g. intercellular adhesion molecule-1 (ICAM-1). Both kinetics follow a pattern with a first peak between 0.5 and 2 h and a second, more sustained activation between 16 and 48 h. We have previously reported on a non-enzymatic triggering of the ceramide signaling cascade as the initiating step in UVA radiation-induced signaling. In this study, we report that this early (0.5-1 h) peak in ceramide content is followed by a second peak that (i) was associated with an increased expression and activity of serine palmitoyltransferase, the key enzyme of ceramide synthesis, (ii) could be prevented by inhibitors of this enzyme, and (iii) was of functional relevance because its inhibition abrogated the second, but not the first peak in UVA radiation-induced ICAM-1 gene expression. We hypothesize that this second peak most likely resulted from a ceramide-mediated autocrine loop, for (i) inhibition of the first ceramide peak resulted in inhibition of the second peak and (ii) cell-permeable ceramides-induced serine palmitoyltransferase expression, activity, and subsequently ceramide content.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Raios Ultravioleta
/
Aciltransferases
/
Queratinócitos
/
Ceramidas
/
Molécula 1 de Adesão Intercelular
/
Comunicação Autócrina
Limite:
Humans
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Alemanha