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Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma

William Griffiths Orcid Logo, Peter Crick, Yuchen Wang, Michael Ogundare, Karin Tuschl, Andrew A Morris, Brian W Bigger, Peter T Clayton, Yuqin Wang Orcid Logo

Free Radical Biology and Medicine

Swansea University Authors: William Griffiths Orcid Logo, Peter Crick, Yuqin Wang Orcid Logo

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DOI (Published version): 10.1016/j.freeradbiomed.2012.07.027

Abstract

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...

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Published in: Free Radical Biology and Medicine
ISSN: 0891-5849
Published: 2012
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URI: https://cronfa.swan.ac.uk/Record/cronfa12875
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last_indexed 2018-02-09T04:43:15Z
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spelling 2013-08-01T07:57:39.5591299 v2 12875 2012-09-26 Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 9e8253a728dc2ad7303ee8928fc85560 Peter Crick Peter Crick true false c92729b58622f9fdf6a0e7d8f4ce5081 0000-0002-3063-3066 Yuqin Wang Yuqin Wang true false 2012-09-26 MEDS 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 Journal Article Free Radical Biology and Medicine 0891-5849 Lipidomics, Sterol, Steroid, Oxysterol, Liquid chromatography, Mass spectrometry, Bile acid, Derivatization, Cerebrotendinous xanthomatosis, Nuclear receptor, G-protein-coupled receptor; Liver X receptor, Free radicals 31 12 2012 2012-12-31 10.1016/j.freeradbiomed.2012.07.027 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University 2013-08-01T07:57:39.5591299 2012-09-26T16:11:44.8562962 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine William Griffiths 0000-0002-4129-6616 1 Peter Crick 2 Yuchen Wang 3 Michael Ogundare 4 Karin Tuschl 5 Andrew A Morris 6 Brian W Bigger 7 Peter T Clayton 8 Yuqin Wang 0000-0002-3063-3066 9
title Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma
spellingShingle Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma
William Griffiths
Peter Crick
Yuqin Wang
title_short Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma
title_full Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma
title_fullStr Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma
title_full_unstemmed Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma
title_sort Analytical strategies for characterization of oxysterol lipidomes: Liver X receptor ligands in plasma
author_id_str_mv 3316b1d1b524be1831790933eed1c26e
9e8253a728dc2ad7303ee8928fc85560
c92729b58622f9fdf6a0e7d8f4ce5081
author_id_fullname_str_mv 3316b1d1b524be1831790933eed1c26e_***_William Griffiths
9e8253a728dc2ad7303ee8928fc85560_***_Peter Crick
c92729b58622f9fdf6a0e7d8f4ce5081_***_Yuqin Wang
author William Griffiths
Peter Crick
Yuqin Wang
author2 William Griffiths
Peter Crick
Yuchen Wang
Michael Ogundare
Karin Tuschl
Andrew A Morris
Brian W Bigger
Peter T Clayton
Yuqin Wang
format Journal article
container_title Free Radical Biology and Medicine
publishDate 2012
institution Swansea University
issn 0891-5849
doi_str_mv 10.1016/j.freeradbiomed.2012.07.027
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description 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
published_date 2012-12-31T06:23:57Z
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score 11.04748

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