The role of cholesterol in UV light B-induced apoptosis.

The role of cholesterol in UV light B-induced apoptosis.
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DOI:
10.1111/j.1751-1097.2011.01038.x
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发表时间:
2012-09
影响因子:
3.3
通讯作者:
Wu S
Wu S
中科院分区:
生物学3区
文献类型:
--
作者:
George KS;Elyassaki W;Wu Q;Wu S

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Modification of major lipid raft components, such as cholesterol and ceramide, plays a role in regulation of programmed cell death under various stimuli. However, the relationship between cholesterol level modification and the activation of apoptotic signaling cascades upon ultraviolet B light has not been established. In this report, we demonstrate that upon UVB irradiation cholesterol levels in membrane rafts of skin cells increase, which leads to Fas aggregation in the rafts. Utilizing a continuous velocity floatation technique, we show that Fas accumulated in the lipid rafts of human melanoma M624 cells after UVB-irradiation. The subsequent events of DISC formation were also detected in the lipid raft fractions. Depletion of cholesterol by methyl-β-cyclodextrin reduces Fas aggregation, while overloading increases. Disruption of lipid rafts also prevents Daxx from dissociating from Fas in the lipid rafts, which is accompanied with a reduced apoptotic, but increased non-apoptotic death of UVB-irradiated human keratinocytes, HaCaT cells. Results indicate that cholesterol located in the plasma membrane of skin cells is required for lipid raft domain formation and activation of UVB-induced apoptosis.
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