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J. Biol. Chem., Vol. 280, Issue 19, 19196-19204, May 13, 2005

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UV-C Light Induces Raft-associated Acid Sphingomyelinase and JNK Activation and Translocation Independently on a Nuclear Signal^*

Alexandra Charruyer, Solène Grazide¶, Christine Bezombes, Sabina Müller, Guy Laurent||, and Jean-Pierre Jaffrézou**

From the INSERM U563, Centre de Physiopathologie de Toulouse-Purpan, Centre Hospitalier Universitaire Purpan, 31024 Toulouse, France and ^||Service d' Hématologie, Centre Hospitalier Universitaire Purpan, 31059 Toulouse, France

The initiation of UV light-induced signaling in mammalian cells is largely considered to be subsequent to DNA damage. Several studies have also described ceramide (CER), a lipid second messenger, as a major contributor in mediating UV light-induced c-Jun N-terminal kinase (JNK) activation and cell death. It is demonstrated here that UV-C light irradiation of U937 cells results in the activation and translocation of a Zn²⁺-independent acid sphingomyelinase, leading to CER accumulation in raft microdomains. These CER-enriched rafts aggregate and play a functional role in JNK activation. The observation that UV-C light also induced CER generation and the externalization of acid sphingomyelinase and JNK in human platelets conclusively rules out the involvement of a nuclear signal generated by DNA damage in the initiation of a UV light response, which is generated at the plasma membrane.

Received for publication, November 15, 2004 , and in revised form, February 22, 2005.

^* This work was supported in part by grants from la Ligue Nationale Contre le Cancer and les Comités Départementaux du Gers, de l'Aveyron, et de la Haute-Garonne (to J.-P. J.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors are recipients of a grant from l'Association pour la Recherche contre le Cancer.

^¶ Recipient of a grant from la Fondation pour la Recherche Médicale.

^** To whom correspondence should be addressed. Tel.: 33-5-62-74-45-62; Fax: 33-5-62-74-45-58; E-mail: jean-pierre.jaffrezou{at}toulouse.inserm.fr.

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