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Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse

Eylan Yutuc Orcid Logo, Peter J. Crick, Eylan Yutuc, Jonas Abdel-Khalik, Ahmed Saeed, Christer Betsholtz, Guillem Genove, Ingemar Björkhem, Yuqin Wang, William Griffiths Orcid Logo

The Journal of Steroid Biochemistry and Molecular Biology, Volume: 195, Start page: 105475

Swansea University Authors: Eylan Yutuc Orcid Logo, William Griffiths Orcid Logo

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DOI (Published version): 10.1016/j.jsbmb.2019.105475

Abstract

While the presence and abundance of the major oxysterols and cholestenoic acids in the circulation is well established, minor cholesterol metabolites may also have biological importance and be of value to investigate. In this study by observing the metabolism of deuterium-labelled cholesterol in the...

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Published in: The Journal of Steroid Biochemistry and Molecular Biology
ISSN: 09600760
Published: 2019
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URI: https://cronfa.swan.ac.uk/Record/cronfa51994
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spelling 2019-10-08T14:46:19.4687026 v2 51994 2019-09-23 Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse 99332f073ce913a9b7d8b6441b17516d 0000-0001-9971-1950 Eylan Yutuc Eylan Yutuc true false 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 2019-09-23 MEDS While the presence and abundance of the major oxysterols and cholestenoic acids in the circulation is well established, minor cholesterol metabolites may also have biological importance and be of value to investigate. In this study by observing the metabolism of deuterium-labelled cholesterol in the pdgfbret/ret mouse, a mouse model with increased vascular permeability in brain, and by studying the sterol content of plasma from the CYP46A1 transgenic mouse overexpressing the human cholesterol 24S-hydroxylase enzyme we have been able to identify a number of minor cholesterol metabolites found in the circulation, make approximate-quantitative measurements and postulate pathways for their formation. These “proof of principle” data may have relevance when using mouse models to mimic human disease and in respect of the increasing possibility of treating human neurodegenerative diseases with pharmaceuticals designed to enhance the activity of CYP46A1 or by adeno-associated virus delivery of CYP46A1. Journal Article The Journal of Steroid Biochemistry and Molecular Biology 195 105475 09600760 24S-hydroxycholesterol, 24S,25-epoxycholesterol, CYP46A1, bile acid biosynthesis, deuterium-enrichment, deuterium-isotope effect, liquid chromatography – mass spectrometry, derivatisation 31 12 2019 2019-12-31 10.1016/j.jsbmb.2019.105475 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University UKRI, BB/N015932/1 2019-10-08T14:46:19.4687026 2019-09-23T09:55:09.3218189 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Eylan Yutuc 0000-0001-9971-1950 1 Peter J. Crick 2 Eylan Yutuc 3 Jonas Abdel-Khalik 4 Ahmed Saeed 5 Christer Betsholtz 6 Guillem Genove 7 Ingemar Björkhem 8 Yuqin Wang 9 William Griffiths 0000-0002-4129-6616 10 0051994-08102019144509.pdf 51994.pdf 2019-10-08T14:45:09.4270000 Output 4944890 application/pdf Version of Record true 2019-10-07T00:00:00.0000000 Released under the terms of a Creative Commons Attribution License (CC-BY). true eng
title Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse
spellingShingle Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse
Eylan Yutuc
William Griffiths
title_short Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse
title_full Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse
title_fullStr Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse
title_full_unstemmed Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse
title_sort Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse
author_id_str_mv 99332f073ce913a9b7d8b6441b17516d
3316b1d1b524be1831790933eed1c26e
author_id_fullname_str_mv 99332f073ce913a9b7d8b6441b17516d_***_Eylan Yutuc
3316b1d1b524be1831790933eed1c26e_***_William Griffiths
author Eylan Yutuc
William Griffiths
author2 Eylan Yutuc
Peter J. Crick
Eylan Yutuc
Jonas Abdel-Khalik
Ahmed Saeed
Christer Betsholtz
Guillem Genove
Ingemar Björkhem
Yuqin Wang
William Griffiths
format Journal article
container_title The Journal of Steroid Biochemistry and Molecular Biology
container_volume 195
container_start_page 105475
publishDate 2019
institution Swansea University
issn 09600760
doi_str_mv 10.1016/j.jsbmb.2019.105475
college_str Faculty of Medicine, Health and Life Sciences
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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 While the presence and abundance of the major oxysterols and cholestenoic acids in the circulation is well established, minor cholesterol metabolites may also have biological importance and be of value to investigate. In this study by observing the metabolism of deuterium-labelled cholesterol in the pdgfbret/ret mouse, a mouse model with increased vascular permeability in brain, and by studying the sterol content of plasma from the CYP46A1 transgenic mouse overexpressing the human cholesterol 24S-hydroxylase enzyme we have been able to identify a number of minor cholesterol metabolites found in the circulation, make approximate-quantitative measurements and postulate pathways for their formation. These “proof of principle” data may have relevance when using mouse models to mimic human disease and in respect of the increasing possibility of treating human neurodegenerative diseases with pharmaceuticals designed to enhance the activity of CYP46A1 or by adeno-associated virus delivery of CYP46A1.
published_date 2019-12-31T04:51:37Z
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