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Kinetic study of low density lipoprotein oxidation by copper

机译:低密度脂蛋白被铜氧化的动力学研究

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摘要

Oxidation of Low Density Lipoprotein (LDL) is regarded as a key event in the development of atherosclerosis. The aim of this study was to investigate effect of various copper concentrations on LDL oxidation kinetic profile as a mechanism in atherosclerosis process. LDL was isolated from plasma and its oxidation with copper was investigated by monitoring the formation of conjugated dienes. Based on time course of the formation of conjugated diene was observed at concentrations of 0.5 to 10 µM copper, represented the conventional kinetics of LDL oxidation with an inhibition period followed by a propagation phase. In contrast, at concentrations of 20 to 50 µM copper, LDL oxidation proceeded after a negligibly short lag-time followed by a distinct propagation phase. At lower copper concentrations of about 0.5 µM, LDL oxidation can be combined in 4 consecutive oxidation phase. The increasing copper concentration (to 10 µM) lowered the first propagation and shortened the seconded inhibition period until they melted into one apparent kinetic phase. But in copper concentrations of about 20 to 50 µM, increasing copper concentration increased the first propagation and the second inhibition but lowered the second propagation phase. The results of this investigation on the copper dependence of the oxidation kinetics suggest that LDL contains two different copper binding sites. Copper bound to the low affinity binding sites with molar ratio of 200 to 500 of copper / LDL. These ions bound to the high affinity binding sites with molar ratio of copper / LDL of 5 to 100.
机译:低密度脂蛋白(LDL)的氧化被认为是动脉粥样硬化发展的关键事件。这项研究的目的是研究各种铜浓度对LDL氧化动力学曲线的影响,作为动脉粥样硬化过程的一种机制。从血浆中分离出LDL,并通过监测共轭二烯的形成来研究其与铜的氧化。基于形成0.5到10 µM铜的共轭二烯形成的时间过程,这代表了LDL氧化的常规动力学,具有抑制期,随后是传播阶段。相反,在浓度为20至50 µM的铜下,LDL氧化在可忽略的短滞后时间之后进行,随后出现明显的传播阶段。在约0.5 µM的较低铜浓度下,LDL氧化可合并为4个连续的氧化阶段。铜浓度的增加(至10 µM)降低了第一次扩散并缩短了二次抑制时间,直到它们熔化成一个明显的动力学相。但是在大约20至50 µM的铜浓度中,增加铜浓度会增加第一传播和第二抑制,但会降低第二传播阶段。该对氧化动力学的铜依赖性的研究结果表明,LDL包含两个不同的铜结合位点。铜以200/500的铜/ LDL摩尔比与低亲和力结合位点结合。这些离子以5:100的铜/ LDL摩尔比与高亲和力结合位点结合。

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