OXYGENATION OF LIPOPROTEINS BY MAMMALIAN LIPOXYGENASES
OXYGENATION OF LIPOPROTEINS BY MAMMALIAN LIPOXYGENASES
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DOI：
10.1111/j.1432-1033.1993.tb17755.x
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发表时间：
1993-04-01
期刊：
影响因子：
--
通讯作者：
KUHN, H
中科院分区：
文献类型：
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作者：
BELKNER, J;WIESNER, R;KUHN, H
氧化修饰将低密度脂蛋白（LDL）转化为其致动脉粥样硬化形式，并且似乎是泡沫细胞形成期间巨噬细胞摄取LDL的必要先决条件。细胞脂氧合酶参与了这一过程。我们研究了纯化的哺乳动物脂氧合酶在体外与人LDL的相互作用，发现兔和人的花生四烯酸15-脂氧合酶能够氧化脂蛋白，如氧摄取和硫代巴比妥酸反应物质的形成所示。此外，在脂氧合酶处理后，在各种脂蛋白类的脂质隔室中检测到含氧多烯脂肪酸，例如13-氢（佩罗）xy-9 Z，11 E-十八碳二烯酸和15-氢（佩罗）xy-5，8，11，13（Z，Z，Z，E）-二十碳四烯酸。超过90%的含氧多烯脂肪酸被发现在酯-脂质馏分，特别是在胆固醇酯，而只有少量的游离氢（佩罗）氧基多烯脂肪酸被检测到。脂氧合酶催化的氧化LDL不限于脂质室，但也导致了共氧化修饰的载脂蛋白，如电泳迁移率的变化和氨基酸侧链的羰基衍生物的形成所示。对脂氧合酶诱导的脂蛋白氧化修饰在动脉粥样硬化发病机制中可能的生物学意义进行了讨论。
Oxidative modification converts low-density lipoprotein (LDL) into its atherogenic form and appears to be a necessary precondition for LDL uptake by macrophages during foam cell formation. Cellular lipoxygenases have been implicated in this process. We studied the interaction of purified mammalian lipoxygenases with human LDL in vitro and found that the arachidonate 15-lipoxygenases of rabbit and man are capable of oxygenating lipoproteins as indicated by oxygen uptake and by the formation of thiobarbituric-acid-reactive substances. Furthermore, oxygenated polyenoic fatty acids, such as 13-hydro(pero)xy-9Z,11E-octadecadienoic acid and 15-hydro(pero)xy-5,8,11,13(Z,Z, Z,E)-eicosatetraenoic acid were detected in the lipid compartment of various lipoproteins classes after lipoxygenase treatment. More than 90% of the oxygenated polyenoic fatty acids were found in the ester-lipid fraction, particularly in the cholesterol esters, whereas only small amounts of free hydro(pero)xy polyenoic fatty acids were detected. Lipoxygenase-catalyzed oxygenation of LDL is not restricted to the lipid compartment but also leads to a cooxidative modification of the apoproteins as indicated by changes in the electrophoretic mobility and by the formation of carbonyl derivatives of amino acid side chains. The possible biological significance of lipoxygenase-induced oxidative modification of lipoproteins in the pathogenesis of atherosclerosis is discussed.