Evidence for a dominant role of lipoxygenase(s) in the oxidation of LDL by mouse peritoneal macrophages.
Evidence for a dominant role of lipoxygenase(s) in the oxidation of LDL by mouse peritoneal macrophages.
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发表时间：
1991-03
影响因子：
6.5
通讯作者：
S. Rankin;S. Parthasarathy;D. Steinberg
中科院分区：
文献类型：
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作者：
S. Rankin;S. Parthasarathy;D. Steinberg
有人提出，低密度脂蛋白（LDL）的氧化修饰是动脉粥样硬化形成过程中的一个关键事件。已经提出了几种机制来解释不同类型的细胞如何修饰LDL。在这项研究中，我们检测了超氧阴离子和细胞脂氧合酶（LO）在巨噬细胞对LDL修饰中的相对作用。超氧化物歧化酶（SOD）抑制巨噬细胞对LDL的氧化，但仅抑制25%。在相同条件下，几种脂氧合酶抑制剂（二十碳四炔酸（ETYA）、吡前列素和A - 64077）几乎完全抑制巨噬细胞对LDL的修饰。超氧化物歧化酶对U937细胞和成纤维细胞对LDL的修饰有更强的抑制作用（分别为32%和64%），但脂氧合酶抑制剂的作用仍然大得多（抑制79% - 100%）。将[1 - 14C]亚油酸与小鼠腹腔巨噬细胞一起孵育，结果通过反相高效液相色谱法将其转化为一种单一的极性更强的产物，该产物与13 - 羟基十八碳二烯酸（13 - HODE）和9 - 羟基十八碳二烯酸（9 - HODE）共同洗脱。当细胞预先与脂氧合酶抑制剂一起孵育时，这种产物的形成被显著抑制。结论是巨噬细胞对LDL的修饰在很大程度上是由脂氧合酶类型的活性介导的。
It has been suggested that the oxidative modification of low density lipoprotein (LDL) is a key event in atherogenesis. Several mechanisms have been proposed to explain how different types of cells modify LDL. In this study we examine the relative contributions of superoxide anions and cellular lipoxygenase (LO) in the modification of LDL by macrophages. Superoxide dismutase (SOD) inhibited LDL oxidation by macrophages but only by 25%. Under the same conditions, several LO inhibitors (eicosatetraynoic acid (ETYA), piriprost, and A-64077) almost completely inhibited the modification of LDL by macrophages. SOD had a greater inhibitory effect on the modification of LDL by U937 cells and fibroblasts (32% and 64%, respectively) but again LO inhibitors had a much greater effect (79 to 100% inhibition). Incubation of [1-14C]linoleic acid with mouse peritoneal macrophages resulted in its conversion to a single more polar product coeluting with 13- and 9-HODE by reverse phase HPLC. When the cells were preincubated with LO inhibitors, formation of this product was significantly inhibited. It is concluded that the modification of LDL by macrophages is mediated in large part by lipoxygenase-type activity.