Folcik V A, Cathcart M K
Department of Cell Biology, Cleveland Clinic Foundation, OH 44195.
J Lipid Res. 1993 Jan;34(1):69-79.
Lipoxygenase (LO) activity has been implicated in the process by which activated human monocytes oxidize normal human low density lipoprotein (LDL) and render it toxic to target cells. Here we examined the role of 5-LO in activated monocyte-mediated LDL modification. Five putative inhibitors of 5-LO (A63162, CGS8515, PF5901, RG6866, and MK886) were used to determine if they prevented activated monocytes from oxidizing LDL. Only RG6866, A63162, and CGS8515 inhibited monocyte-mediated LDL oxidation. Nonspecific effects of these drugs on LDL oxidation by activated monocytes were examined. RG6866 and A63162 were both found to be general antioxidants at their effective concentrations. CGS8515 was toxic at its effective concentration. A63162, CGS8515, and RG6866 also inhibited 15-LO activity in vitro. MK886 and PF5901 did not exhibit the nonspecific effects above and did not inhibit monocyte-mediated LDL oxidation, whereas both MK886 and PF5901 inhibited production of 5-LO metabolites by activated monocytes at concentrations that had no effect on LDL oxidation by the activated monocytes. Since neither of these agents inhibited LDL oxidation, we conclude that 5-LO is not involved in human monocyte oxidation of LDL. The possibility that a cellular 12- or 15-LO is involved in human monocyte-mediated LDL oxidation remains to be evaluated.
脂氧合酶（LO）活性与活化的人单核细胞氧化正常人低密度脂蛋白（LDL）并使其对靶细胞产生毒性的过程有关。在此，我们研究了5-LO在活化单核细胞介导的LDL修饰中的作用。使用了5种推测的5-LO抑制剂（A63162、CGS8515、PF5901、RG6866和MK886）来确定它们是否能阻止活化的单核细胞氧化LDL。只有RG6866、A63162和CGS8515抑制了单核细胞介导的LDL氧化。研究了这些药物对活化单核细胞氧化LDL的非特异性作用。发现RG6866和A63162在其有效浓度下均为一般抗氧化剂。CGS8515在其有效浓度下具有毒性。A63162、CGS8515和RG6866在体外也抑制15-LO活性。MK886和PF5901未表现出上述非特异性作用，也未抑制单核细胞介导的LDL氧化，而MK886和PF5901在对活化单核细胞氧化LDL无影响的浓度下均抑制活化单核细胞产生5-LO代谢产物。由于这两种药物均未抑制LDL氧化，我们得出结论，5-LO不参与人单核细胞对LDL的氧化。细胞12-或15-LO是否参与人单核细胞介导的LDL氧化仍有待评估。
