Khalil A, Fülöp T
Institut Universitaire de Gériatrie de Sherbrooke and Département de Médecine, Université de Sherbrooke, QC, Canada.
Can J Physiol Pharmacol. 2001 Feb;79(2):114-21.
The oxidation of low-density lipoproteins is the first step in the complex process leading to atherosclerosis. The aim of our study was to compare the kinetics of low density lipoprotein oxidation induced by copper ions or by oxygen free radicals generated by 60Co gamma-rays. The effects of copper concentration and irradiation dose-rate on LDL peroxidation kinetics were also studied. The oxidation of LDL was followed by the measurement of conjugated diene, hydroperoxides, and thiobarbituric acid reactive substance formation as well as alpha-tocopherol disappearance. In the case of gamma irradiation, the lag-phase before the onset of lipid peroxidation was inversely correlated to the radiation dose-rate. The radiation chemical rates (nu) increased with increasing dose-rate. Copper-induced LDL peroxidation followed two kinetic patterns: a slow kinetic for copper concentrations between 5-20 microM, and a fast kinetic for a copper concentration of 40 microM. The concentration-dependent oxidation kinetics suggest the existence of a saturable copper binding site on apo-B. When compared with gamma-rays, copper ions act as drastic and powerful oxidants only at higher concentrations (> or = 40 microM).
低密度脂蛋白的氧化是导致动脉粥样硬化这一复杂过程的第一步。我们研究的目的是比较铜离子或60Coγ射线产生的氧自由基诱导的低密度脂蛋白氧化动力学。还研究了铜浓度和辐照剂量率对低密度脂蛋白过氧化动力学的影响。通过测量共轭二烯、氢过氧化物、硫代巴比妥酸反应性物质的形成以及α-生育酚的消失来跟踪低密度脂蛋白的氧化。在γ辐照的情况下，脂质过氧化开始前的延迟期与辐射剂量率呈负相关。辐射化学速率（ν）随剂量率增加而增加。铜诱导的低密度脂蛋白过氧化遵循两种动力学模式：铜浓度在5-20μM之间时为慢动力学，铜浓度为40μM时为快动力学。浓度依赖性氧化动力学表明载脂蛋白B上存在一个可饱和的铜结合位点。与γ射线相比，铜离子仅在较高浓度（≥40μM）时才作为剧烈且强大的氧化剂起作用。
