Jerlich A, Pitt A R, Schaur R J, Spickett C M
Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, United Kingdom.
Free Radic Biol Med. 2000 Mar 1;28(5):673-82. doi: 10.1016/s0891-5849(99)00273-7.
A wealth of evidence now indicates that low-density lipoprotein (LDL) must be modified to promote atherosclerosis, and that this may involve oxidants released by phagocytes. Many studies of oxidative damage in atherosclerosis previously have concentrated on damage by nonhalogenated oxidants, but HOCl is a highly toxic oxidant produced by myeloperoxidase in phagocytes, which is also likely to be important in the disease pathogenesis. Currently some controversy exists over the products resulting from reaction of HOCl with LDL lipids, in particular regarding whether predominantly chlorohydrins or lipid peroxides are formed. In this study LC-MS of phosphatidylcholines in human LDL treated either with HOCl or the myeloperoxidase system was used as a specific method to detect chlorohydrin and peroxide formation simultaneously, and with comparable sensitivity. Chlorohydrin products from lipids containing oleic, linoleic and arachidonic acids were detected, but no hydroperoxides of linoleoyl or arachidonoyl lipids could be observed. This study provides the first direct evidence that lipid chlorohydrins rather than peroxides are the major products of HOCl- or myeloperoxidase-treated LDL phospholipids. This in turn provides important information required for the study of oxidative damage in vivo which will allow the type and source of oxidants involved in the pathology of atherosclerosis to be investigated.
大量证据表明，低密度脂蛋白（LDL）必须经过修饰才能促进动脉粥样硬化，而这可能涉及吞噬细胞释放的氧化剂。此前，许多关于动脉粥样硬化中氧化损伤的研究都集中在非卤化氧化剂造成的损伤上，但次氯酸（HOCl）是吞噬细胞中髓过氧化物酶产生的一种剧毒氧化剂，在该疾病的发病机制中可能也很重要。目前，关于HOCl与LDL脂质反应产生的产物存在一些争议，特别是主要生成的是氯醇还是脂质过氧化物。在本研究中，使用LC-MS检测用HOCl或髓过氧化物酶系统处理的人LDL中的磷脂酰胆碱，作为同时检测氯醇和过氧化物形成的特定方法，且具有相当的灵敏度。检测到了含有油酸、亚油酸和花生四烯酸的脂质产生的氯醇产物，但未观察到亚油酰基或花生四烯酰基脂质的氢过氧化物。本研究提供了首个直接证据，表明脂质氯醇而非过氧化物是HOCl或髓过氧化物酶处理的LDL磷脂的主要产物。这反过来为体内氧化损伤研究提供了重要信息，有助于研究动脉粥样硬化病理过程中涉及的氧化剂类型和来源。
