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Ceramide and raft signaling are linked with each other in UVA radiation-induced gene expression

Oncogene volume 27, pages 4768–4778 (2008)Cite this article

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.

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Abbreviations

ßMCD:

ß-methylcyclodextrin

7α-OH:

7α-hydroxycholesterol

7ß-OH:

7ß-hydroxycholesterol

7-Ketochol:

7-ketocholesterol

AP-2:

activator protein 2

Camp:

campesterol

Chol:

cholesterol

CholOOH:

cholesterol hydroperoxide

ICAM-1:

intercellular adhesion molecule-1

IFN-g:

Interferon-γ

NHEK:

normal human epidermal keratinocytes

Sito:

β sitosterol

Stigma:

stigmasterol

UVA:

ultraviolet A

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Acknowledgements

We thank H Sies and K-D Kroencke (Duesseldorf), as well as E Proksch (Kiel), for helpful discussion and critical review of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft Grant SFB 503, project B2, and SFB 728.

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Authors and Affiliations

  1. Zellbiologie, Institut fuer Umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University Duesseldorf gGmbH, Duesseldorf, Germany

    S Grether-Beck, M Salahshour-Fard, A Timmer, H Brenden, I Felsner, R Walli & J Krutmann

  2. Internal Medicine IV, University of Heidelberg, Heidelberg, Germany

    J Füllekrug

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  1. S Grether-Beck
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Correspondence to S Grether-Beck.

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Grether-Beck, S., Salahshour-Fard, M., Timmer, A. et al. Ceramide and raft signaling are linked with each other in UVA radiation-induced gene expression. Oncogene 27, 4768–4778 (2008). https://doi.org/10.1038/onc.2008.116

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