Lipid rafts mediate ultraviolet light-induced fas aggregation in M624 melanoma cells
Lipid rafts mediate ultraviolet light-induced fas aggregation in M624 melanoma cells
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DOI：
10.1562/2005-12-09-ra-748
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发表时间：
2006-05-01
影响因子：
3.3
通讯作者：
Wu, Shiyong
中科院分区：
文献类型：
--
作者：
Elyassaki, Walid;Wu, Shiyong
紫外线 (UV) 通过 Fas 配体独立途径诱导 Fas 受体聚集。然而，紫外线诱导Fas受体聚集的机制尚不清楚。在本报告中，我们表明脂筏介导紫外线诱导的 Fas 聚集。我们的数据显示，UV 会诱导 Fas 受体在 25-5% Optiprep 连续梯度中重新分布。含有脂筏的梯度组分中 Fas 受体的量显着增加，并且与 FADD 和 caspase-8 的增加相关。我们的数据还表明，脂筏部分中活性二聚体形式的 caspase-8 (p44/p41) 有所增加。此外，我们的数据表明，脂筏的主要成分胆固醇在紫外线照射后仅在脂筏部分中显着减少。然而，另一种主要脂筏成分神经酰胺在紫外线照射后在所有梯度组分中均匀增加。这些结果表明，紫外线改变了主要脂筏成分的组成，从而导致 Fas 受体和 FADD 的募集，随后激活 caspase-8。根据我们的结果，我们提出了一种新的机制，紫外线通过膜脂筏介导的信号通路诱导细胞凋亡。
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-receptor 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.