Targeted lipidomic analysis of oxysterols in the embryonic central nervous system.
Targeted lipidomic analysis of oxysterols in the embryonic central nervous system.
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DOI：
10.1039/b819502a
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发表时间：
2009-05
影响因子：
--
通讯作者：
Griffiths WJ
中科院分区：
文献类型：
--
作者：
Wang Y;Sousa KM;Bodin K;Theofilopoulos S;Sacchetti P;Hornshaw M;Woffendin G;Karu K;Sjövall J;Arenas E;Griffiths WJ
在这项研究中，两个区域的胚胎（E11）小鼠中枢神经系统（CNS）已被描绘为他们的未酯化甾醇含量。使用高效液相色谱法（HPLC）-质谱法（MS）和串联质谱法（MSn），在皮质（Ctx）和脊髓（Sc）中鉴定出低水平的氧化甾醇（估计为2 - 165 ng/g湿重）。已鉴定的氧固醇包括7α-、7β-、22 R-、24 S-、25-和27-羟基胆固醇; 24，25-和24，27-二羟基胆固醇;以及24 S，25-环氧胆固醇。其中，24 S-羟基胆固醇仅在大脑中生物合成。与脑中24 S-羟基胆固醇水平约为40 μg/g的成年小鼠相比，本文报告的24 S-羟基胆固醇水平（Ctx中估计为26 ng/g，Sc中估计为13 ng/g）极低。有趣的是，两个CNS区域中的24 S，25-环氧胆固醇水平（Ctx中估计为165 ng/g，Sc中估计为91 ng/g）略高于羟基胆固醇水平。这种氧化固醇通过甲羟戊酸途径的分流与胆固醇平行形成，其相对较高的丰度可能反映了该发育阶段胆固醇合成速率较高。通过气相色谱-质谱法（GC-MS）测定胆固醇水平（Ctx中估计为1.25 mg/g，Sc中估计为1.15 mg/g）及其前体。在两个CNS区域中，发现胆固醇水平低于成人报告的水平，但与胆固醇相关的胆固醇前体水平高于成人，表明胆固醇合成速率较高。总之，我们的数据提供了证据，内源性氧固醇的存在下，在两个大脑区域的发展中枢神经系统。此外，虽然大多数参与羟基甾醇合成的酶在E11时活性最低，但我们的研究结果表明，甲羟戊酸途径显着活跃，为大脑发育过程中24 S，25-epoxycholesterol的功能开辟了可能性。
In this study two regions of embryonic (E11) mouse central nervous system (CNS) have been profiled for their unesterified sterol content. Using high-performance liquid chromatography (HPLC) – mass spectrometry (MS) and tandem mass spectrometry (MSn) low levels of oxysterols (estimated 2 – 165 ng/g wet weight) were identified in cortex (Ctx) and spinal cord (Sc). The identified oxysterols include 7α-, 7β-, 22R-, 24S-, 25- and 27-hydroxycholesterol; 24,25- and 24,27-dihydroxycholesterol; and 24S,25-epoxycholesterol. Of these, 24S-hydroxycholesterol is biosynthesised exclusively in brain. In comparison to adult mouse where the 24S-hydroxycholesterol level is about 40 μg/g in brain the level of 24S-hydroxycholesterol reported here (estimated 26 ng/g in Ctx and 13 ng/g in Sc) is extremely low. Interestingly, the level of 24S,25-epoxycholesterol in both CNS regions (estimated 165 ng/g in Ctx and 91 ng/g in Sc) is somewhat higher than the levels of the hydroxycholesterols. This oxysterol is formed in parallel to cholesterol via a shunt of the mevalonate pathway and its comparatively high abundance may be a reflection of a high rate of cholesterol synthesis at this stage of development. Levels of cholesterol (estimated 1.25 mg/g in Ctx and 1.15 mg/g in Sc) and its precursors were determined by gas chromatography – mass spectrometry (GC-MS). In both CNS regions cholesterol levels were found to be lower than those reported in the adult, but in relation to cholesterol the levels of cholesterol precursors were higher than found in adult indicating a high rate of cholesterol synthesis. In summary, our data provide evidence for the presence of endogenous oxysterols in two brain regions of the developing CNS. Moreover, while most of the enzymes involved in hydroxysterol synthesis are minimally active at E11, our results suggest that the mevalonate pathway is significantly active, opening up the possibility for a function of 24S,25-epoxycholesterol during brain development.
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DOI：
10.1002/ar.a.20015
发表时间：
2004-04-01
期刊：
ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY
影响因子：
--
作者：
Annicotte, JS;Schoonjans, K;Auwerx, J
通讯作者：
Auwerx, J
影响因子：
4.8
作者：
Bjorkhem, I;Lutjohann, D;Wennmalm, A
通讯作者：
Wennmalm, A
DOI：
10.1073/pnas.96.1.266
发表时间：
1999-01-05
影响因子：
11.1
作者：
Janowski, BA;Grogan, MJ;Mangelsdorf, DJ
通讯作者：
Mangelsdorf, DJ
影响因子：
2
作者：
Jiang, Xuntian;Ory, Daniel S.;Han, Xianlin
通讯作者：
Han, Xianlin
DOI：
10.1073/pnas.0711599105
发表时间：
2008-02-12
影响因子：
11.1
作者：
Kim, Hyun-Jin;Fan, Xiaotang;Gustafsson, Jan-Ake
通讯作者：
Gustafsson, Jan-Ake