Protection of membrane cholesterol by sphingomyelin against free radical-mediated oxidation.
Protection of membrane cholesterol by sphingomyelin against free radical-mediated oxidation.
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DOI：
10.1016/j.freeradbiomed.2006.02.005
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发表时间：
2006-06
影响因子：
7.4
通讯作者：
R. Sargis;P. Subbaiah
中科院分区：
文献类型：
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作者：
R. Sargis;P. Subbaiah
尽管自由基介导的游离胆固醇（FC）氧化对调节固醇的生成和动脉粥样硬化至关重要，但这一过程的生理调节机制尚不清楚。我们验证了鞘磷脂（SM）的假设，鞘磷脂是细胞膜上的一种主要磷脂，与FC密切相关，由于其独特的结构和对甾醇的亲和力，可以保护FC免受氧化。我们使用磷脂酰胆碱（PC）脂质体含有不同量的SM，放射性FC或荧光类似物脱氢麦角甾醇（DHE），并测定了甾醇在2,2 ' -偶氮双（2-氨基丙烷盐酸盐）（AAPH）存在下的氧化衰变。在脂质体中掺入25 mol%的SM可抑制FC或DHE氧化达50%。这种抑制作用是磷脂中SM所特有的，鞘磷脂酶可以消除这种抑制作用。SM在氧化反应中不会被降解，其作用与氧化剂的性质无关，因为它还可以抑制FeSO4/抗坏血酸和胆固醇氧化酶对甾醇的氧化。这些研究表明SM在调节胆固醇被自由基氧化过程中具有生理作用。
Although the free radical-mediated oxidation of free cholesterol (FC) is critical in the generation of regulatory sterols and in atherogenesis, the physiological regulation of this process is poorly understood. We tested the hypothesis that sphingomyelin (SM), a major phospholipid of cell membranes, which is closely associated with FC, protects FC against oxidation, because of its unique structure, and affinity to the sterol. We employed phosphatidylcholine (PC) liposomes containing varying amounts of SM, and either radioactive FC or a fluorescent analog, dehydroergosterol (DHE), and determined the oxidative decay of the sterol in presence of 2,2′-azo-bis(2-amidinopropane hydrochloride) (AAPH). Incorporation of 25 mol% of SM in the liposomes inhibited the oxidation of FC or DHE by up to 50%. This inhibition was specific for SM among phospholipids, and was abolished by sphingomyelinase treatment. SM was not degraded during the oxidation reaction, and its effect was not dependent on the nature of the oxidizing agent, because it also inhibited sterol oxidation by FeSO4/ascorbate, and by cholesterol oxidase. These studies show that SM plays a physiological role in the regulation of cholesterol oxidation by free radicals.