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Targeted lipidomic analysis of oxysterols in the embryonic central nervous system / Yuqin Wang; Kyle M Sousa; Karl Bodin; Spyridon Theofilopoulos; Paola Sacchetti; Martin Hornshaw; Gary Woffendin; Kersti Karu; Jan Sjövall; Ernest Arenas; William J Griffiths

Molecular BioSystems, Volume: 5, Issue: 5, Start page: 529

Swansea University Author: Griffiths, William

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DOI (Published version): 10.1039/B819502A

Abstract

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 w...

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Published in: Molecular BioSystems
ISSN: 1742-206X 1742-2051
Published: 2009
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URI: https://cronfa.swan.ac.uk/Record/cronfa10950
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spelling 2013-08-05T09:15:45Z v2 10950 2012-06-05 Targeted lipidomic analysis of oxysterols in the embryonic central nervous system William Griffiths William Griffiths true 0000-0002-4129-6616 false 3316b1d1b524be1831790933eed1c26e 3e4851c27dfd9cf65adbd476d1f7a3bf zaxgD1SlXhR1pE5DoDi9bR8j7kl4zZwebz0wEHEQAUk= 2012-06-05 BMS 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. Journal article Molecular BioSystems 5 5 529 1742-206X 1742-2051 0 0 2009 2009-01-01 10.1039/B819502A Swansea University Medical School CMED BMS Biomarkers and genes 2013-08-05T09:15:45Z 2012-06-05T16:47:04Z Swansea University Medical School Medicine Yuqin Wang 1 Kyle M Sousa 2 Karl Bodin 3 Spyridon Theofilopoulos 4 Paola Sacchetti 5 Martin Hornshaw 6 Gary Woffendin 7 Kersti Karu 8 Jan Sjövall 9 Ernest Arenas 10 William J Griffiths 11
title Targeted lipidomic analysis of oxysterols in the embryonic central nervous system
spellingShingle Targeted lipidomic analysis of oxysterols in the embryonic central nervous system
Griffiths, William
title_short Targeted lipidomic analysis of oxysterols in the embryonic central nervous system
title_full Targeted lipidomic analysis of oxysterols in the embryonic central nervous system
title_fullStr Targeted lipidomic analysis of oxysterols in the embryonic central nervous system
title_full_unstemmed Targeted lipidomic analysis of oxysterols in the embryonic central nervous system
title_sort Targeted lipidomic analysis of oxysterols in the embryonic central nervous system
author_id_str_mv 3316b1d1b524be1831790933eed1c26e
author_id_fullname_str_mv 3316b1d1b524be1831790933eed1c26e_***_Griffiths, William
author Griffiths, William
author2 Yuqin Wang
Kyle M Sousa
Karl Bodin
Spyridon Theofilopoulos
Paola Sacchetti
Martin Hornshaw
Gary Woffendin
Kersti Karu
Jan Sjövall
Ernest Arenas
William J Griffiths
format Journal article
container_title Molecular BioSystems
container_volume 5
container_issue 5
container_start_page 529
publishDate 2009
institution Swansea University
issn 1742-206X
1742-2051
doi_str_mv 10.1039/B819502A
college_str Swansea University Medical School
hierarchytype
hierarchy_top_id swanseauniversitymedicalschool
hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
document_store_str 0
active_str 1
researchgroup_str Biomarkers and genes
description 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.
published_date 2009-01-01T04:08:00Z
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