Chantepie Sandrine, Malle Ernst, Sattler Wolfgang, Chapman M John, Kontush Anatol
Université Pierre et Marie Curie-Paris 6, UMR S939 "Dyslipydemia, Inflammation and Atherosclerosis in Metabolic Diseases", F-75013 Paris, France.
Arch Biochem Biophys. 2009 Jul 1;487(1):28-35. doi: 10.1016/j.abb.2009.05.005. Epub 2009 May 21.
The heme protein myeloperoxidase (MPO) functions as a catalyst for lipoprotein oxidation. Hypochlorous acid (HOCl), a potent two-electron oxidant formed by the MPO-H(2)O(2)-chloride system of activated phagocytes, modifies antiatherogenic high-density lipoprotein (HDL). The structural heterogeneity and oxidative susceptibility of HDL particle subfractions were probed with HOCl. All distinct five HDL subfraction were modified by HOCl as demonstrated by the consumption of tryptophan residues and free amino groups, cross-linking of apolipoprotein AI, formation of HOCl-modified epitopes, increased electrophoretic mobility and altered content of unsaturated fatty acids in HDL subclasses. Small, dense HDL3 were less susceptible to oxidative modification than large, light HDL2 on a total mass basis at a fixed HOCl:HDL mass ratio of 1:32, but in contrast not on a particle number basis at a fixed HOCl:HDL molar ratio of 97:1. We conclude that structural and physicochemical differences between HDL subclasses do not influence their intrinsic susceptibility to oxidative attack by HOCl.
血红素蛋白髓过氧化物酶（MPO）作为脂蛋白氧化的催化剂发挥作用。次氯酸（HOCl）是活化吞噬细胞的MPO-H₂O₂-氯化物系统形成的一种强效双电子氧化剂，可修饰抗动脉粥样硬化的高密度脂蛋白（HDL）。用HOCl探究了HDL颗粒亚组分的结构异质性和氧化敏感性。所有五种不同的HDL亚组分均被HOCl修饰，表现为色氨酸残基和游离氨基的消耗、载脂蛋白AI的交联、HOCl修饰表位的形成、电泳迁移率增加以及HDL亚类中不饱和脂肪酸含量改变。在固定的HOCl:HDL质量比为1:32时，基于总质量，小而致密的HDL3比大而轻的HDL2对氧化修饰的敏感性更低，但相反，在固定的HOCl:HDL摩尔比为97:1时，基于颗粒数量则并非如此。我们得出结论，HDL亚类之间的结构和物理化学差异不会影响它们对HOCl氧化攻击的固有敏感性。
