Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma
Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma
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DOI：
10.1016/j.freeradbiomed.2012.07.027
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发表时间：
2013-06-01
影响因子：
7.4
通讯作者：
Wang, Yuqin
中科院分区：
文献类型：
--
作者：
Griffiths, William J.;Crick, Peter J.;Wang, Yuqin
胆汁酸、胆汁醇和激素类固醇代表脊椎动物胆固醇代谢的最终生物活性产物。然而，在它们的形成中的中间体，包括氧固醇和异戊烯酸，也具有已知的，例如，作为核和G蛋白偶联受体的配体，以及未知的调节活性。源自胆固醇结构的分子的潜在多样性非常广泛，并且它们在生物材料中的丰度范围超过几个数量级。在这里，我们描述了应用酶辅助衍生甾醇分析（EADSA）结合液相色谱-电喷雾电离-质谱法，以确定氧化甾醇和巴豆酸代谢组的人血浆。使用EADSA对成人血浆进行定量分析，可检测到30多种来自胆固醇的代谢产物，其中一些是核受体LXR、FXR和胆固醇X受体或G蛋白偶联受体EB病毒诱导基因2的配体。EADSA技术在筛查胆固醇代谢和生物合成的先天性缺陷中的潜力通过患有腱性黄瘤病的患者的独特血浆谱来证明。所描述的分析方法容易适用于分析其它生物流体，包括脑脊液，以及组织，例如，脑，其中核和G蛋白偶联受体可能具有重要的调节作用。(c)2012 Elsevier Inc. All rights reserved.
Bile acids, bile alcohols, and hormonal steroids represent the ultimate biologically active products of cholesterol metabolism in vertebrates. However, intermediates in their formation, including oxysterols and cholestenoic acids, also possess known, e.g., as ligands to nuclear and G-protein-coupled receptors, and unknown regulatory activities. The potential diversity of molecules originating from the cholesterol structure is very broad and their abundance in biological materials ranges over several orders of magnitude. Here we describe the application of enzyme-assisted derivatization for sterol analysis (EADSA) in combination with liquid chromatography-electrospray ionization-mass spectrometry to define the oxysterol and cholestenoic acid metabolomes of human plasma. Quantitative profiling of adult plasma using EADSA leads to the detection of over 30 metabolites derived from cholesterol, some of which are ligands to the nuclear receptors LXR, FXR, and pregnane X receptor or the G-protein-coupled receptor Epstein-Barr virus-induced gene 2. The potential of the EADSA technique in screening for inborn errors of cholesterol metabolism and biosynthesis is demonstrated by the unique plasma profile of patients suffering from cerebrotendinous xanthomatosis. The analytical methods described are easily adapted to the analysis of other biological fluids, including cerebrospinal fluid, and also tissues, e.g., brain, in which nuclear and G-protein-coupled receptors may have important regulatory roles. (c) 2012 Elsevier Inc. All rights reserved.