Noguchi N, Nakano K, Aratani Y, Koyama H, Kodama T, Niki E
Research Center for Advanced Science and Technology, The University of Tokyo, Komaba, Meguro, Tokyo 153-8904, Japan. nonoriko@oxygen. rcast.u-tokyo.ac.jp
J Biochem. 2000 Jun;127(6):971-6. doi: 10.1093/oxfordjournals.jbchem.a022713.
Low density lipoprotein was oxidized by neutrophils derived from either C57BL/6 mice or myeloperoxidase (MPO)-knockout mice. The generation of superoxide from neutrophils of MPO-knockout mice was about 70% of that from wild-type mice. The extent of the oxidation of human low density lipoprotein (LDL) by phorbol myristate acetate (PMA)-activated neutrophils of wild-type and MPO-knockout mice was assessed by measuring consumption of a-tocopherol and formation of phosphatidylcholine hydroperoxide (PCOOH) and cholesteryl ester hydroperoxide (CEOOH). Little consumption of a-tocopherol was observed in both oxidations. It was found, however, that lipid hydroperoxides were accumulated with time in both oxidations and that the rates of formation of PCOOH and CEOOH in the oxidation by MPO-knockout neutrophils were about 66 and 44% of those by wild-type neutrophils, respectively. The lipid peroxidation was completely inhibited by adding superoxide dismutase (SOD) in both cases. The addition of L-tyrosine and SOD enhanced lipid peroxidation of LDL induced by wild-type neutrophils but not by MPO-knockout ones. These results suggest that, regardless of their MPO activity, neutrophils induce lipid peroxidation of LDL by a superoxide-dependent pathway, and that MPO-catalyzed lipid peroxidation is enhanced by the presence of an appropriate amount of free tyrosine and further enhanced by SOD.
低密度脂蛋白被来自C57BL/6小鼠或髓过氧化物酶（MPO）基因敲除小鼠的中性粒细胞氧化。MPO基因敲除小鼠中性粒细胞产生超氧化物的量约为野生型小鼠的70%。通过测量α-生育酚的消耗以及磷脂酰胆碱氢过氧化物（PCOOH）和胆固醇酯氢过氧化物（CEOOH）的形成，评估野生型和MPO基因敲除小鼠经佛波酯（PMA）激活的中性粒细胞对人低密度脂蛋白（LDL）的氧化程度。在两种氧化过程中均未观察到α-生育酚的大量消耗。然而，发现两种氧化过程中脂质氢过氧化物均随时间积累，并且MPO基因敲除中性粒细胞氧化过程中PCOOH和CEOOH的形成速率分别约为野生型中性粒细胞的66%和44%。在两种情况下，添加超氧化物歧化酶（SOD）均可完全抑制脂质过氧化。添加L-酪氨酸和SOD可增强野生型中性粒细胞诱导的LDL脂质过氧化，但对MPO基因敲除中性粒细胞诱导的脂质过氧化无增强作用。这些结果表明，无论中性粒细胞的MPO活性如何，其均可通过超氧化物依赖性途径诱导LDL脂质过氧化，并且适量游离酪氨酸的存在可增强MPO催化的脂质过氧化，而SOD可进一步增强该过程。
