Oxidation of sitosterol and transport of its 7-oxygenated products from different tissues in humans and ApoE knockout mice

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dc.contributor.author Schött, Hans-Frieder
dc.contributor.author Baumgartner, Sabine
dc.contributor.author Husche, Constanze
dc.contributor.author Luister, Alexandra
dc.contributor.author Friedrichs, Silvia
dc.contributor.author Miller, Charlotte M.
dc.contributor.author McCarthy, Florence O.
dc.contributor.author Plat, Jogchum
dc.contributor.author Laufs, Ulrich
dc.contributor.author Weingärtner, Oliver
dc.contributor.author Lütjohann, Dieter
dc.date.accessioned 2018-02-12T10:17:04Z
dc.date.available 2018-02-12T10:17:04Z
dc.date.issued 2016-04-27
dc.identifier.citation Schött, H.-F., Baumgartner, S., Husche, C., Luister, A., Friedrichs, S., Miller, C. M., McCarthy, F. O., Plat, J., LaufS, U., Weingärtner, O. and Lütjohann, D. (2017) ‘Oxidation of sitosterol and transport of its 7-oxygenated products from different tissues in humans and ApoE knockout mice’, Journal of Steroid Biochemistry and Molecular Biology, 169, pp. 145-151. doi:10.1016/j.jsbmb.2016.04.011 en
dc.identifier.volume 169 en
dc.identifier.startpage 145 en
dc.identifier.endpage 151 en
dc.identifier.issn 0960-0760
dc.identifier.uri http://hdl.handle.net/10468/5438
dc.identifier.doi 10.1016/j.jsbmb.2016.04.011
dc.description.abstract The most common phytosterols in the human diet are sitosterol and campesterol, which originate exclusively from plant derived food. These phytosterols are taken up by NPC1L1 transport from the intestine into the enterocytes together with cholesterol and other xenosterols. Phytosterols are selectively pumped back from the enterocytes into the intestinal lumen and on the liver site from hepatocytes into bile by heterodimeric ABCG5/G8 transporters. Like cholesterol, both phytosterols are prone to ring and side chain oxidation. It could be shown that oxyphytosterols, found in atherosclerotic tissue, are most likely of in situ oxidation (Schött et al.; Biochem. Biophys. Res. Commun. 2014 Apr 11;446(3):805-10). However, up to now, the entire mechanism of phytosterol oxidation is not clearly understood. Here, we provide further information about the oxidation of sitosterol and the transport of its oxidation products out of tissue. Our survey includes data of 104 severe aortic stenosis patients that underwent an elective aortic valve cusp replacement. We studied their phytosterol concentrations, as well as absolute and substrate corrected oxyphytosterol levels in plasma and valve cusp tissue. In addition, we also examined phytosterol and oxyphytosterol concentrations in plasma and tissues (from brain and liver) of 10 male ApoE knockout mice. The ratio of 7-oxygenated-sitosterol-to-sitosterol exceeds the ratio for 7-oxygenated-campesterol-to-campesterol in plasma and tissue of both humans and mice. This finding indicates that sitosterol is oxidized to a higher amount than campesterol and that a selective oxidative mechanism might exist which can differentiate between certain phytosterols. Secondly, the concentrations of oxyphytosterols found in plasma and tissue support the idea that oxysitosterols are preferably transported out of individual tissues. Selective oxidation of sitosterol and preferred transport of sitosterol oxidation products out of tissue seem to be a metabolic pathway of forced sitosterol clearance from tissue compartments. en
dc.description.sponsorship Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Grant 014-012-010; NWO TOP Grant No. 91208006) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier Ltd. en
dc.rights © 2016, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. en
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Sitosterol en
dc.subject Phytosterol en
dc.subject Oxyphytosterol en
dc.subject Oxidation en
dc.subject Transport en
dc.subject Metabolism en
dc.title Oxidation of sitosterol and transport of its 7-oxygenated products from different tissues in humans and ApoE knockout mice en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Florence Mccarthy, Chemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: f.mccarthy@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2018-02-06T11:12:45Z
dc.description.version Accepted Version en
dc.internal.rssid 424716954
dc.contributor.funder Universität des Saarlandes en
dc.contributor.funder Nederlandse Organisatie voor Wetenschappelijk Onderzoek en
dc.contributor.funder Seventh Framework Programme en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal of Steroid Biochemistry and Molecular Biology en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress f.mccarthy@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/211696/EU/THERAPEUTIC AND PREVENTIVE IMPACT OF NUTRITIONAL LIPIDS ON NEURONAL AND COGNITIVE PERFORMANCE IN AGING, ALZHEIMER’S DISEASE AND VASCULAR DEMENTIA/LIPIDIDIET en


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© 2016, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. Except where otherwise noted, this item's license is described as © 2016, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
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