Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis
Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis
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DOI：
10.1194/jlr.c400005-jlr200
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发表时间：
2005-02-01
影响因子：
6.5
通讯作者：
Masterman, T
中科院分区：
文献类型：
--
作者：
Leoni, V;Lütjohann, D;Masterman, T
在最近的出版物[Diestel，A.，O. Aktas，D.哈克尔岛Hake，S.迈耶角S.雷恩河Nitsch、E Zipp和O.乌尔里希2003.神经炎症过程中胆固醇分解产物激活小胶质细胞聚（ADP-核糖）聚合酶-1：脱髓鞘和神经元损伤之间的联系J失效Med.198：1729-1740]，11例多发性硬化症（MS）患者的脑脊液（CSF）中报告了极高水平的7-氧代胆固醇[7.4 +/- 0.3 mg/l（平均值：+/- SEM）]。据报告，12名患有其他神经系统疾病的受试者的相应水平为0.5 +/- 0.1 mg/l。发现如此高水平的7-氧代胆固醇会导致活脑组织的神经元损伤。使用一种基于同位素稀释-质谱法和厌氧条件的高精度7-氧代胆固醇测定方法，我们发现29名瑞典MS患者CSF中的7-氧代胆固醇水平仅为1.2 mug/l（中位数，范围为0.4至4.6 mug/l），低于先前报告水平的1/1，000。24名瑞典对照患者的CSF中7-氧代胆固醇水平为0.9 mug/l（0.3-2.3 mug/l），略低于但显著低于MS患者的CSF水平（P = 0.002）。在CSF中内源性胆固醇的体外诱导的脂质过氧化增加了7-氧合胆固醇代谢物，特别是7-氧代胆固醇的水平，高达类似于0.3 mg/l。这些结果是讨论有关的事实，即7-氧合类固醇容易人工形成的胆固醇自动氧化过程中的工作程序和分析的甾醇和氧化甾醇从生物样品。Leoni，V，D. Lutjohann和T.马斯特曼脑脊液中7-氧代胆固醇的水平比多发性硬化症报告的低一千倍以上。
In a recent publication [Diestel, A., O. Aktas, D. Hackel, I. Hake, S. Meier, C. S. Raine, R. Nitsch, E Zipp, and O. Ullrich. 2003. Activation of microglial poly (ADP-ribose)polymerase-1 by cholesterol breakdown products during neuroinflammation: a link between demyelination and neuronal damage. J Exp. Med. 198: 1729-1740], extremely high levels of 7-oxocholesterol were reported in cerebrospinal fluid (CSF) of 11 patients with multiple sclerosis (MS) [7.4 +/- 0.3 mg/l (mean :+/- SEM)]. The corresponding level of 12 subjects with other kinds of neurological diseases was reported to be 0.5 +/- 0.1 mg/l. Such high levels of 7-oxocholesterol were found to cause neuronal damage of living brain tissues. Using a highly accurate method for an assay of 7-oxocholesterol based on isotope dilution-mass spectrometry and anaerobic conditions during workup, we found that the level of 7-oxocholesterol in CSF from 29 Swedish patients with MS was only 1.2 mug/l (median, ranging from 0.4 to 4.6 mug/l), less than 1/1,000th of the previously reported level. The level of 7-oxocholesterol in CSF from 24 Swedish control patients was 0.9 mug/l (0.3-2.3 mug/l), slightly but significantly lower than the CSF level in MS patients (P = 0.002). In vitro-induced lipid peroxidation of the endogenous cholesterol in CSF increased the level of 7-oxygenated cholesterol metabolites, particularly 7-oxocholesterol, up to similar to0.3 mg/l.jlr These results are discussed in relation to the fact that 7-oxygenated steroids are easily artificially formed by autoxidation of cholesterol during workup procedures and analysis of sterols and oxysterols from biological samples.-Leoni, V, D. Lutjohann, and T. Masterman. Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis.