Morgan J, Leake D S
Rheumatology Section, Veterans Administration Hospital, San Diego, CA 92161, USA.
J Lipid Res. 1995 Dec;36(12):2504-12.
Oxidized low density lipoprotein (LDL) may play a significant role in atherosclerosis. We have investigated the effect of pH on the oxidation of LDL by iron or copper. When LDL was oxidized by iron in the presence of cysteine in either Hanks' balanced salt solution (HBSS) or Ham's F-10 medium, an acidic pH greatly decreased the lag period and increased the rate of formation of hydroperoxides and thiobarbituric acid-reactive substances (TBARS), and increased its uptake by macrophages. There was a dose-dependent increase of LDL oxidation at acidic pH in the presence of increasing concentrations of cysteine. When LDL was oxidized by copper in HBSS, an acidic pH increased the lag phase before the rapid formation of conjugated dienes, hydroperoxides, and TBARS, but increased its uptake by macrophages. Similar results were obtained using Ham's F-10 medium. Cysteine (100 microM) inhibited the modification of LDL by copper in HBSS at both pH 7.4 and 5.5 As atherosclerotic lesions may be acidic, these observations may help to explain why LDL oxidation occurs locally at these sites.
氧化型低密度脂蛋白（LDL）可能在动脉粥样硬化中起重要作用。我们研究了pH对铁或铜氧化LDL的影响。当LDL在汉克斯平衡盐溶液（HBSS）或哈姆F-10培养基中在半胱氨酸存在下被铁氧化时，酸性pH大大缩短了滞后期，增加了氢过氧化物和硫代巴比妥酸反应性物质（TBARS）的形成速率，并增加了其被巨噬细胞的摄取。在酸性pH下，随着半胱氨酸浓度增加，LDL氧化呈剂量依赖性增加。当LDL在HBSS中被铜氧化时，酸性pH增加了共轭二烯、氢过氧化物和TBARS快速形成之前的滞后期，但增加了其被巨噬细胞的摄取。使用哈姆F-10培养基也获得了类似结果。半胱氨酸（100 microM）在pH 7.4和5.5时均抑制了HBSS中铜对LDL的修饰。由于动脉粥样硬化病变可能呈酸性，这些观察结果可能有助于解释为什么LDL氧化在这些部位局部发生。
