Yan L J, Lodge J K, Traber M G, Matsugo S, Packer L
Department of Molecular and Cell Biology, University of California at Berkeley 94720-3200, USA.
J Lipid Res. 1997 May;38(5):992-1001.
The purpose of this study was to evaluate the mechanisms of apolipoprotein B (apoB) modification during oxidation of human low density lipoproteins (LDL) mediated either by copper or by hypochlorite (HOCl). The kinetics of protein carbonyl formation, the relationship of apoB carbonyl formation to lipid peroxidation, and the loss of apoB lysine residues were determined. During copper-mediated LDL oxidation, apoB carbonyls appeared to increase slowly, displayed saturation kinetics in response to increasing copper concentrations, and correlated with lipid peroxidation. During HOCl-mediated LDL oxidation, apoB carbonyls increased with increasing HOCl concentrations reaching plateau with time; however, lipid peroxidation was not observed. During copper-mediated but not during HOCl-mediated LDL oxidation, LDL vitamin E was depleted. ApoB carbonyls formed more efficiently during copper-mediated LDL oxidation at low (< 5 microM) copper concentrations compared with higher copper concentrations or during HOCl-mediated LDL oxidation. The differences in oxidation kinetics between copper- and HOCl-mediated LDL oxidation support the concept that the binding of copper to LDL is a site specific process, and suggest that HOCl modifies apoB amino acids randomly.
本研究的目的是评估在铜或次氯酸盐（HOCl）介导的人低密度脂蛋白（LDL）氧化过程中载脂蛋白B（apoB）修饰的机制。测定了蛋白质羰基形成的动力学、apoB羰基形成与脂质过氧化的关系以及apoB赖氨酸残基的损失。在铜介导的LDL氧化过程中，apoB羰基似乎缓慢增加，对铜浓度增加呈现饱和动力学，并与脂质过氧化相关。在HOCl介导的LDL氧化过程中，apoB羰基随HOCl浓度增加而增加，随时间达到平台期；然而，未观察到脂质过氧化。在铜介导而非HOCl介导的LDL氧化过程中，LDL维生素E被耗尽。与较高铜浓度或HOCl介导的LDL氧化相比，在低（<5 microM）铜浓度的铜介导的LDL氧化过程中，apoB羰基形成更有效。铜和HOCl介导的LDL氧化动力学的差异支持铜与LDL的结合是一个位点特异性过程的概念，并表明HOCl随机修饰apoB氨基酸。
