Kühn H, Belkner J, Suzuki H, Yamamoto S
Institute of Biochemistry, University Clinicum Charité, Medical Faculty of the Humboldt University, Berlin, Germany.
J Lipid Res. 1994 Oct;35(10):1749-59.
Cellular lipoxygenases have been implicated in foam cell formation during the early stages of atherogenesis. We studied the interaction of lipoxygenases of different positional specificities with human lipoproteins and found that the arachidonate 15-lipoxygenases of rabbit and humans and the arachidonate 12-lipoxygenase of porcine leukocytes oxygenate lipoproteins as indicated by the formation of oxygenated lipids and changes in electrophoretic mobility of low density lipoprotein. The arachidonate 12-lipoxygenase of human platelets, the recombinant arachidonate 5-lipoxygenase of human leukocyte, and the soybean lipoxygenase I were less effective in oxidizing human LDL. As a major oxygenation product, esterified 13S-hydro(pero)xy-9Z,11E-octadecadienoic acid was identified for both the rabbit reticulocyte 15- and the porcine leukocyte 12-lipoxygenase. In addition, esterified 15S-hydro(pero)xy-5,8,11,13(Z,Z,Z,E)-eicosatetraenoic acid (for the rabbit 15-lipoxygenase) and 12S-hydro(pero)xy-5,8,10,14(Z,Z,E,Z)-eicosatetraenoic acid (for the porcine 12-lipoxygenase) as well as small amounts of racemic 9-hydro(pero)xy-10,12-octadecadienoic acid isomers were detected. More than 90% of the oxygenated polyenoic fatty acids were found in the ester lipid fraction, particularly in the cholesteryl esters and in various phospholipid classes (phosphatidylcholine and phosphatidylethanolamine). The possible biological significance of lipoxygenase-induced oxidative modification of lipoproteins in the pathogenesis of atherosclerosis is discussed.
细胞脂氧合酶与动脉粥样硬化发生早期的泡沫细胞形成有关。我们研究了不同位置特异性的脂氧合酶与人类脂蛋白的相互作用，发现兔和人的花生四烯酸15 -脂氧合酶以及猪白细胞的花生四烯酸12 -脂氧合酶可使脂蛋白氧化，这可通过氧化脂质的形成和低密度脂蛋白电泳迁移率的变化来表明。人血小板的花生四烯酸12 -脂氧合酶、人白细胞的重组花生四烯酸5 -脂氧合酶以及大豆脂氧合酶I在氧化人低密度脂蛋白方面效果较差。作为主要的氧化产物，已鉴定出兔网织红细胞15 -脂氧合酶和猪白细胞12 -脂氧合酶的酯化13S -氢（过）氧-9Z,11E -十八碳二烯酸。此外，还检测到酯化的15S -氢（过）氧-5,8,11,13(Z,Z,Z,E)-二十碳四烯酸（兔15 -脂氧合酶）和12S -氢（过）氧-5,8,10,14(Z,Z,E,Z)-二十碳四烯酸（猪12 -脂氧合酶）以及少量外消旋9 -氢（过）氧-10,12 -十八碳二烯酸异构体。超过90%的氧化多烯脂肪酸存在于酯脂质部分，特别是在胆固醇酯和各种磷脂类（磷脂酰胆碱和磷脂酰乙醇胺）中。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。
