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1 May 2006 Lipid Rafts Mediate Ultraviolet Light–induced Fas Aggregation in M624 Melanoma Cells
Walid Elyassaki, Shiyong Wu
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Ultraviolet light (UV) induces aggregation of Fas-receptor through a Fas-ligand–independent pathway. However, the mechanism of ultraviolet light-induced Fas-receptor aggregation is not known. In this report, we show that lipid rafts mediate ultraviolet light–induced aggregation of Fas. Our data show that UV induces a redistribution of Fas-receptor in a 25–5% Optiprep continuous gradient. The amount of Fas-receptorS is significantly increased in a gradient fraction that contain lipid rafts and is associated with an increase of FADD and caspase-8. Our data also show that the active dimeric form of caspase-8 (p44/p41) is increased in the lipid raft fraction. In addition, our data show that cholesterol, a major component of lipid rafts, is significantly reduced in only the lipid raft fractions after UV-irradiation. However, ceramide, another major lipid raft component, is increased evenly in all gradient fractions after UV-irradiation. These results suggest that UV alters the composition of major lipid raft components, which leads to the recruitment of Fas-receptor and FADD, with subsequent activation of caspase-8. Based on our results, we propose a novel mechanism by which UV induces apoptosis through a membrane lipid raft–mediated signaling pathway.

Walid Elyassaki and Shiyong Wu "Lipid Rafts Mediate Ultraviolet Light–induced Fas Aggregation in M624 Melanoma Cells," Photochemistry and Photobiology 82(3), 787-792, (1 May 2006).
Received: 7 September 2005; Accepted: 1 January 2006; Published: 1 May 2006

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