Lipid rafts mediate ultraviolet light-induced Fas aggregation in M624 melanoma cells.
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.
Elyassaki
Walid
W
The Department of Chemistry and Biochemistry and Edison Biotechnology Institute, Ohio University, Athens, USA.
Wu
Shiyong
S
D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D019281:Dimerization; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D021962:Membrane Microdomains / Q000502:physiology*; D014466:Ultraviolet Rays; D019014:fas Receptor / Q000378:metabolism / Q000528:radiation effects*
D019014:fas Receptor