MECHANISM OF APOLIPOPROTEIN B 100 THIOL DEPLETION DURING OXIDATION OF LDL

LDL 氧化过程中载脂蛋白 B 100 硫醇消耗的机制

• 批准号: 6307907
• 负责人: ERIC FERGUSON
• 金额: $ 1.13万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6307907
• 关键词: bioengineering /biomedical engineering; biological products; biomaterials; biomedical resource; lipids

Oxidation of low-density lipoprotein (LDL) is recognized to be a key step in atherogenesis. Previous studies show that LDL contains low molecular weight antioxidants such as vitamin E, beta-carotene, and ubiquinol, that can retard oxidative modification. In this report, we have evaluated the antioxidant potential of apolipoprotein B-100 (apo-B) thiols during LDL oxidation. Both apo-B thiols and vitamin E were depleted concomitantly during the lag phase of Cu(2+)-mediated LDL oxidation. The rate of thiol depletion was significantly inhibited by the lipophilic spin trap N-tert-butyl-alpha-phenylnitrone (PBN) but not by the water-soluble spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). Blocking apo-B thiols with sulfhydryl modifying agents increased the oxidizability of LDL. As with Cu(2+), peroxynitrite also caused depletion of apo-B thiols, and again thiol depletion was inhibited by PBN but not by POBN. A PBN-lipid-derived radical adduct was observed by the electron spin resonance (ESR) technique during oxidation of LDL with peroxynitrite. We conclude that apo-B thiol depletion is mediated by lipid peroxidation, prior to the onset of the propagation phase of LDL oxidation. The implications of apo-B thiols as intrinsic antioxidants of LDL are discussed.

低密度脂蛋白(LDL)的氧化被认为是一种 动脉粥样硬化形成的关键步骤。先前的研究表明，低密度脂蛋白含有 低分子抗氧化剂，如维生素E，β-胡萝卜素， 以及泛喹酚，它可以延缓氧化修饰。在这 据报道，我们已经评估了载脂蛋白的抗氧化潜力 低密度脂蛋白氧化过程中的B-100(apo-B)硫醇。载脂蛋白-B硫醇和 维生素E在营养不良的滞后期也随之耗尽。 Cu2+介导的低密度脂蛋白氧化。硫醇耗竭的速度是 被亲脂的自旋陷阱显著抑制 N-叔丁基-α-苯基硝酮(PBN)，但不是由水溶性 自旋陷阱α-(4-吡啶-1-氧化物)-N-叔丁基硝酮(POBN)。 用巯基修饰剂封闭载脂蛋白-B硫醇可增加 低密度脂蛋白的氧化性。与铜(2+)一样，过亚硝酸根也会引起 抑制载脂蛋白B硫醇的消耗，又一次抑制硫醇的消耗。 PBN，而不是POBN。观察到一种PBN-脂质衍生的自由基加合物 用电子自旋共振(ESR)技术研究低密度脂蛋白氧化 用过亚硝酸根。我们得出结论，载脂蛋白B硫醇耗竭是 在繁殖开始之前，由脂质过氧化介导 低密度脂蛋白氧化阶段。载脂蛋白-B硫醇作为内源性的含义 讨论了低密度脂蛋白的抗氧化剂。