Kalyanaraman B, Darley-Usmar V, Struck A, Hogg N, Parthasarathy S
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226, USA.
J Lipid Res. 1995 May;36(5):1037-45.
The peroxidation of low density lipoprotein (LDL) may play an important role in the modification of the lipoprotein to an atherogenic form. The oxidation of LDL by peroxidases has recently been suggested as a model for in vivo transition metal ion-independent oxidation of LDL (Wieland, E., S. Parthasarathy, and D. Steinberg. 1993. Proc. Natl. Acad. Sci. USA. 90: 5929-5933). It is possible that in vivo the peroxidase activities of proteins, such as prostaglandin synthase and myeloperoxidase, promote LDL oxidation. We have used horseradish peroxidase (HRP) and H2O2 as a model of peroxidase-dependent oxidation of LDL and we observed the following during HRP/H2O2-initiated LDL oxidation. i) The oxidation of alpha-tocopherol occurred with the concomitant formation of alpha-tocopheroxyl radical. This was followed by the production of an apolipoprotein B (apoB)-derived radical. The apoB radical and the alpha-tocopheroxyl radical were formed under both aerobic and anaerobic conditions. ii) Inclusion of N-t-butyl-alpha-phenylnitrone (PBN) did not inhibit alpha-tocopheroxyl radical formation. The ESR spectrum of a PBN/LDL-lipid derived adduct was observed after prolonged incubation. iii) There was formation of conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substances. Our data indicate that HRP/H2O2 oxidizes both alpha-tocopherol and apoB to the corresponding radicals and concomitantly initiates lipid peroxidation.
低密度脂蛋白（LDL）的过氧化作用可能在脂蛋白转变为致动脉粥样化形式的过程中发挥重要作用。最近有人提出，过氧化物酶对LDL的氧化作用可作为体内LDL非依赖过渡金属离子氧化的模型（维兰德，E.，S. 帕尔塔萨拉蒂，和D. 斯坦伯格。1993年。《美国国家科学院院刊》。90: 5929 - 5933）。体内蛋白质如前列腺素合酶和髓过氧化物酶的过氧化物酶活性有可能促进LDL氧化。我们使用辣根过氧化物酶（HRP）和H2O2作为LDL过氧化物酶依赖性氧化的模型，在HRP/H2O2引发的LDL氧化过程中观察到以下情况。i）α-生育酚的氧化伴随着α-生育酚自由基的形成。随后产生载脂蛋白B（apoB）衍生的自由基。apoB自由基和α-生育酚自由基在有氧和无氧条件下均会形成。ii）加入N-叔丁基-α-苯基硝酮（PBN）不会抑制α-生育酚自由基的形成。长时间孵育后观察到PBN/LDL-脂质衍生加合物的电子顺磁共振光谱。iii）有共轭二烯、脂质氢过氧化物和硫代巴比妥酸反应性物质的形成。我们的数据表明，HRP/H2O2将α-生育酚和apoB都氧化为相应的自由基，并同时引发脂质过氧化。
