Thomas S R, Witting P K, Stocker R
Biochemistry Group, Heart Research Institute, Camperdown, NSW, Australia.
Biofactors. 1999;9(2-4):207-24. doi: 10.1002/biof.5520090216.
Substantial evidence implicates oxidative modification of low density lipoprotein (LDL) as an important event contributing to atherogenesis. As a result, the elucidation of the molecular mechanisms by which LDL is oxidized and how such oxidation is prevented by antioxidants has been a significant research focus. Studies on the antioxidation of LDL lipids have focused primarily on alpha-tocopherol (alpha-TOH), biologically and chemically the most active form of vitamin E and quantitatively the major lipid-soluble antioxidant in extracts prepared from human LDL. In addition to alpha-TOH, plasma LDL also contains low levels of ubiquinol-10 (CoQ10H2; the reduced form of coenzyme Q10). Recent studies have shown that in oxidizing plasma lipoproteins alpha-TOH can exhibit anti- or pro-oxidant activities for the lipoprotein's lipids exposed to a vast array of oxidants. This article reviews the molecular action of alpha-TOH in LDL undergoing "mild" radical-initiated lipid peroxidation, and discusses how small levels of CoQ10H2 can represent an efficient antioxidant defence for lipoprotein lipids. We also comment on the levels alpha-TOH, CoQ10H2 and lipid oxidation products in the intima of patients with coronary artery disease and report on preliminary studies examining the effect of coenzyme Q10 supplementation on atherogenesis in apolipoprotein E knockout mice.
大量证据表明，低密度脂蛋白（LDL）的氧化修饰是动脉粥样硬化发生的一个重要事件。因此，阐明LDL被氧化的分子机制以及抗氧化剂如何防止这种氧化一直是重要的研究重点。关于LDL脂质抗氧化作用的研究主要集中在α-生育酚（α-TOH）上，它是维生素E在生物学和化学上最具活性的形式，也是从人LDL提取物中定量的主要脂溶性抗氧化剂。除α-TOH外，血浆LDL还含有低水平的泛醇-10（辅酶Q10H2；辅酶Q10的还原形式）。最近的研究表明，在氧化血浆脂蛋白时，α-TOH对暴露于大量氧化剂的脂蛋白脂质可表现出抗氧化或促氧化活性。本文综述了α-TOH在经历“轻度”自由基引发的脂质过氧化的LDL中的分子作用，并讨论了低水平的辅酶Q10H2如何能对脂蛋白脂质起到有效的抗氧化防御作用。我们还评论了冠状动脉疾病患者内膜中α-TOH、辅酶Q10H2和脂质氧化产物的水平，并报告了关于辅酶Q10补充剂对载脂蛋白E基因敲除小鼠动脉粥样硬化发生影响的初步研究。
