Disruption of lipid rafts causes apoptotic cell death in HaCaT keratinocytes
Disruption of lipid rafts causes apoptotic cell death in HaCaT keratinocytes
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DOI：
10.1111/j.0906-6705.2005.00283.x
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发表时间：
2005-04-01
影响因子：
3.6
通讯作者：
Gajkowska, B
中科院分区：
文献类型：
--
作者：
Bang, B;Gniadecki, R;Gajkowska, B
脂筏是质膜上富含胆固醇的微结构域。许多膜蛋白的功能活性，包括死亡和生长因子受体，取决于它们在脂筏中的插入。我们之前已经证明了角质形成细胞中脂筏的存在，并表明脂筏参与了角质形成细胞增殖和代谢活性的控制。在这项工作中，我们研究了脂质筏破坏对HaCaT角化细胞存活的影响。脂筏可以被破坏或重新排列与胆固醇靶向洗涤剂：甲基- β -环糊精和filipin III。此外，通过特定氧化酶氧化胆固醇或通过美伐他汀阻断胆固醇合成对脂筏有类似的影响。所有胆固醇修饰物质均以浓度依赖性方式引起细胞死亡。对环糊精作用的更详细研究表明，浓度>= 0.5% （w/v）时，凋亡细胞死亡。筏破坏导致细胞凋亡的分子机制尚不清楚，但似乎并不依赖于胆固醇修饰化合物所施加的膜通透性或细胞周期阻滞。
Lipid rafts are cholesterol-enriched microdomains in plasma membranes. The functional activity of many membrane proteins, including death and growth factor receptors, depends on their insertion in lipid rafts. We have previously demonstrated the presence of lipid rafts in keratinocytes and shown that lipid rafts are involved in the control of keratinocyte proliferation and metabolic activity. In this work, we investigated the effect of lipid-raft disruption on HaCaT keratinocyte survival. Lipid rafts could be disrupted or rearranged with cholesterol-targeting detergents: methyl-beta-cyclodextrin and filipin III. Moreover, cholesterol oxidation by a specific oxidase or blocking of cholesterol synthesis by mevastatin had a similar effect on lipid rafts. All cholesterol-modifying substances caused cell death in a concentration-dependent manner. More detailed studies on the effects of cyclodextrin revealed apoptotic cell death at concentrations >= 0.5% (w/v). The molecular mechanism of apoptosis precipitated by raft disruption remains unknown but does not seem to be dependent of either membrane permeabilization or cell-cycle arrest imposed by cholesterol-modifying compounds.