Lipid peroxidation induces cholesterol domain formation in model membranes
Lipid peroxidation induces cholesterol domain formation in model membranes
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DOI：
10.1074/jbc.m507587200
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发表时间：
2005-11-25
影响因子：
4.8
通讯作者：
Mason, RP
中科院分区：
文献类型：
--
作者：
Jacob, RF;Mason, RP
许多报道已经证实，脂质过氧化通过改变膜组分的基本物理性质和结构组织而导致细胞损伤。多不饱和磷脂的氧化修饰已被证明，特别是，改变分子间的包装，热力学和膜双分子层的相参数。本研究采用小角x射线衍射法测定了氧化应激对膜磷脂和甾醇组织的影响。在不同浓度的胆固醇和生理条件下脂质过氧化条件下，制备了富含二烯油基磷脂酰胆碱的模型膜。当胆固醇与磷脂摩尔比（C/P）低至0.4时，脂质过氧化诱导形成离散的、膜限制的胆固醇结构域，其单位细胞周期或d空间值为34埃。胆固醇结构域的形成与脂质过氧化氢水平直接相关，并被维生素e抑制。在没有氧化应激的情况下，只有在C/P比为1.0或更高时，才观察到类似的胆固醇结构域。除了固醇组织的改变外，脂质过氧化还引起了整体膜结构的可重复性变化，包括周围的低固醇膜双分子层的宽度减少了10埃。这些数据提供了直接证据，证明脂质过氧化改变了膜脂的基本组织和结构，从而可能导致衰老和氧化应激相关疾病期间膜功能的变化。
Numerous reports have established that lipid peroxidation contributes to cell injury by altering the basic physical properties and structural organization of membrane components. Oxidative modification of polyunsaturated phospholipids has been shown, in particular, to alter the intermolecular packing, thermodynamic, and phase parameters of the membrane bilayer. In this study, the effects of oxidative stress on membrane phospholipid and sterol organization were measured using small angle x-ray diffraction approaches. Model membranes enriched in dilinoleoylphosphatidylcholine were prepared at various concentrations of cholesterol and subjected to lipid peroxidation at physiologic conditions. At cholesterol-to-phospholipid mole ratios ( C/P) as low as 0.4, lipid peroxidation induced the formation of discrete, membrane-restricted cholesterol domains having a unit cell periodicity or d-space value of 34 angstrom. The formation of cholesterol domains correlated directly with lipid hydroperoxide levels and was inhibited by treatment with vitamin E. In the absence of oxidative stress, similar cholesterol domains were observed only at C/P ratios of 1.0 or higher. In addition to changes in sterol organization, lipid peroxidation also caused reproducible changes in overall membrane structure, including a 10 angstrom reduction in the width of the surrounding, sterol-poor membrane bilayer. These data provided direct evidence that lipid peroxidation alters the essential organization and structure of membrane lipids in a manner that may contribute to changes in membrane function during aging and oxidative stress-related disorders.