Belkner J, Wiesner R, Rathman J, Barnett J, Sigal E, Kühn H
Institute of Biochemistry, Medical School (Charité), Humboldt University, Berlin, Germany.
Eur J Biochem. 1993 Apr 1;213(1):251-61. doi: 10.1111/j.1432-1033.1993.tb17755.x.
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.
氧化修饰将低密度脂蛋白（LDL）转变为其致动脉粥样化形式，并且似乎是巨噬细胞在泡沫细胞形成过程中摄取LDL的必要前提条件。细胞脂氧合酶参与了这一过程。我们在体外研究了纯化的哺乳动物脂氧合酶与人LDL的相互作用，发现兔和人的花生四烯酸15-脂氧合酶能够使脂蛋白氧化，这可通过氧摄取以及硫代巴比妥酸反应性物质的形成来表明。此外，在脂氧合酶处理后的各种脂蛋白类别的脂质部分中检测到了氧化的多烯脂肪酸，如13-氢（过氧）-9Z,11E-十八碳二烯酸和15-氢（过氧）-5,8,11,13（Z,Z,Z,E）-二十碳四烯酸。超过90%的氧化多烯脂肪酸存在于酯脂质部分，特别是胆固醇酯中，而仅检测到少量游离的氢（过氧）多烯脂肪酸。脂氧合酶催化的LDL氧化不仅限于脂质部分，还会导致载脂蛋白的共氧化修饰，这可通过电泳迁移率的变化以及氨基酸侧链羰基衍生物的形成来表明。本文讨论了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的可能生物学意义。
