Superoxide initiates oxidation of low density lipoprotein by human monocytes.
Superoxide initiates oxidation of low density lipoprotein by human monocytes.
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超氧化物引发人单核细胞对低密度脂蛋白的氧化。
DOI：
10.1161/01.atv.7.1.55
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Chait,A
中科院分区：
文献类型：
--
作者：
Hiramatsu,K;Rosen,H;Heinecke,JW;Wolfbauer,G;Chait,A
以人单核细胞为研究对象，研究超氧化物在低密度脂蛋白(LDL)氧化中的作用。根据过氧化脂质含量测定，未受刺激的细胞产生很少的超氧化物或低密度脂蛋白氧化。佛波酯(PMA)刺激细胞后，细胞内超氧化物的生成和低密度脂蛋白的氧化均增加。单核细胞介导的低密度脂蛋白氧化是时间和细胞数量依赖的，铁(10微米)的存在显著增强了这一作用。通过早期加入超氧化物歧化酶(SOD)来抑制反应，表明启动低密度脂蛋白的氧化需要超氧化物。低密度脂蛋白氧化的繁殖是不依赖于超氧化物的，因为后来加入超氧化物歧化酶导致对低密度脂蛋白氧化的抑制逐渐减弱。低密度脂蛋白氧化的传播在一定程度上也是不依赖于细胞的，当与细胞接触1至8小时后去除单个核细胞时，低密度脂蛋白的持续氧化表明。最佳的低密度脂蛋白氧化需要在整个孵育期内单个核细胞的存在，这表明除了超氧化物外，细胞因素在低密度脂蛋白氧化中发挥了作用。超氧化物在单核细胞氧化低密度脂蛋白中的作用的进一步证据是通过来自遗传缺陷的患者的细胞获得的，这些患者有超氧化物生成(慢性肉芽肿疾病)或髓过氧化物酶的遗传缺陷。来自慢性肉芽肿性疾病患者的PMA刺激的细胞既不产生超氧化物也不产生修饰的低密度脂蛋白。将低密度脂蛋白与髓过氧化物酶缺乏症患者的细胞(其中超氧化物产生正常或增加)孵育，可导致等同于正常细胞的脂蛋白氧化。其他氧化反应的抑制剂也进行了测试。
Human mononuclear cells were used to evaluate the role of superoxide in the oxidation of low density lipoprotein (LDL). Unstimulated cells produced little superoxide or LDL oxidation as assayed by lipid peroxide content. Stimulation of the cells with phorbol myristate acetate (PMA) resulted in an increase both in superoxide production and in LDL oxidation. Mononuclear cell-mediated LDL oxidation was time- and cell number-dependent and was markedly enhanced by the presence of Fe (10 microM). Superoxide was required for the initiation of LDL oxidation as indicated by inhibition of the reaction by early addition of superoxide dismutase (SOD). Propagation of LDL oxidation was superoxide-independent, since the later addition of SOD resulted in progressively less inhibition of LDL oxidation. Propagation of LDL oxidation also was, in part, cell-independent as indicated by continued oxidation of LDL when mononuclear cells were removed following a 1 to 8 hour period with cells. Optimal LDL oxidation required the presence of mononuclear cells throughout the incubation period, suggesting that cellular factors in addition to superoxide play a role in LDL oxidation. Further evidence for the role of superoxide in the oxidation of LDL by mononuclear cells was obtained with cells from patients with genetic deficiencies of either superoxide generation (chronic granulomatous disease) or myeloperoxidase. PMA-stimulated cells from a patient with chronic granulomatous disease neither generated superoxide nor modified LDL. Incubation of LDL with cells from a patient with myeloperoxidase deficiency (in which superoxide production is normal or increased) resulted in oxidation of the lipoprotein equivalent to that observed with normal cells. Other inhibitors of oxidation reactions also were tested.(ABSTRACT TRUNCATED AT 250 WORDS)