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HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
Open Biology, Volume: 13, Issue: 5
Swansea University Authors: Alison Dickson, Eylan Yutuc , Cathy Thornton , Yuqin Wang , William Griffiths
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DOI (Published version): 10.1098/rsob.220313
Abstract
Most biologically active oxysterols have a 3β-hydroxy-5-ene function in thering system with an additional site of oxidation at C-7 or on the side-chain. In blood plasma oxysterols with a 7α-hydroxy group are also observed with the alternative 3-oxo-4-ene function in the ring system formed by ubiquit...
Published in: | Open Biology |
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ISSN: | 2046-2441 |
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The Royal Society
2023
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URI: | https://cronfa.swan.ac.uk/Record/cronfa61629 |
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In blood plasma oxysterols with a 7α-hydroxy group are also observed with the alternative 3-oxo-4-ene function in the ring system formed by ubiquitously expressed 3β-hydroxy-Δ5-C27-steroid oxidoreduc-taseΔ5-isomerase, HSD3B7. However, oxysterols without a 7α-hydroxy group are not substrates for HSD3B7 and are not usually observed with the 3-oxo-4-ene function. Here we report the unexpected identification of oxysterols in plasma derived from umbilical cord blood and blood from pregnant women taken before delivery at 37+ weeks of gestation, of side-chain oxysterols with a 3-oxo-4-ene function but no 7α-hydroxy group.These 3-oxo-4-ene oxysterols were also identified in placenta, leading to the hypothesis that they may be formed by a previously unrecognized 3β-hydroxy-Δ5-C27-steroid oxidoreductaseΔ5-isomerase activity of HSD3B1,an enzyme which is highly expressed in placenta. Proof-of-principle experiments confirmed that HSD3B1 has this activity. We speculate thatHSD3B1 in placenta is the source of the unexpected 3-oxo-4-ene oxysterols in cord and pregnant women’s plasma and may have a role in controlling the abundance of biologically active oxysterols delivered to the fetus.</abstract><type>Journal Article</type><journal>Open Biology</journal><volume>13</volume><journalNumber>5</journalNumber><paginationStart/><paginationEnd/><publisher>The Royal Society</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>2046-2441</issnElectronic><keywords>placenta, mass spectrometry, bile acid, pregnancy, HSD3B1, oxysterol</keywords><publishedDay>1</publishedDay><publishedMonth>5</publishedMonth><publishedYear>2023</publishedYear><publishedDate>2023-05-01</publishedDate><doi>10.1098/rsob.220313</doi><url>http://dx.doi.org/10.1098/rsob.220313</url><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>SU Library paid the OA fee (TA Institutional Deal)</apcterm><funders/><projectreference/><lastEdited>2023-11-15T12:41:02.8708421</lastEdited><Created>2022-10-21T09:46:59.5002597</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Alison</firstname><surname>Dickson</surname><order>1</order></author><author><firstname>Eylan</firstname><surname>Yutuc</surname><orcid>0000-0001-9971-1950</orcid><order>2</order></author><author><firstname>Cathy</firstname><surname>Thornton</surname><orcid>0000-0002-5153-573X</orcid><order>3</order></author><author><firstname>James E.</firstname><surname>Dunford</surname><orcid>0000-0002-9932-4042</orcid><order>4</order></author><author><firstname>Udo</firstname><surname>Oppermann</surname><order>5</order></author><author><firstname>Yuqin</firstname><surname>Wang</surname><orcid>0000-0002-3063-3066</orcid><order>6</order></author><author><firstname>William</firstname><surname>Griffiths</surname><orcid>0000-0002-4129-6616</orcid><order>7</order></author></authors><documents><document><filename>61629__27805__17987f2615a14b3eac84c8f5f4b7fd2f.pdf</filename><originalFilename>61629.pdf</originalFilename><uploaded>2023-06-12T14:24:36.9565555</uploaded><type>Output</type><contentLength>3685048</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>2023 The Authors. 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2023-11-15T12:41:02.8708421 v2 61629 2022-10-21 HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta 82dc4360769527a5f3a0cd9d85cdff40 Alison Dickson Alison Dickson true false 99332f073ce913a9b7d8b6441b17516d 0000-0001-9971-1950 Eylan Yutuc Eylan Yutuc true false c71a7a4be7361094d046d312202bce0c 0000-0002-5153-573X Cathy Thornton Cathy Thornton true false c92729b58622f9fdf6a0e7d8f4ce5081 0000-0002-3063-3066 Yuqin Wang Yuqin Wang true false 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 2022-10-21 MEDS Most biologically active oxysterols have a 3β-hydroxy-5-ene function in thering system with an additional site of oxidation at C-7 or on the side-chain. In blood plasma oxysterols with a 7α-hydroxy group are also observed with the alternative 3-oxo-4-ene function in the ring system formed by ubiquitously expressed 3β-hydroxy-Δ5-C27-steroid oxidoreduc-taseΔ5-isomerase, HSD3B7. However, oxysterols without a 7α-hydroxy group are not substrates for HSD3B7 and are not usually observed with the 3-oxo-4-ene function. Here we report the unexpected identification of oxysterols in plasma derived from umbilical cord blood and blood from pregnant women taken before delivery at 37+ weeks of gestation, of side-chain oxysterols with a 3-oxo-4-ene function but no 7α-hydroxy group.These 3-oxo-4-ene oxysterols were also identified in placenta, leading to the hypothesis that they may be formed by a previously unrecognized 3β-hydroxy-Δ5-C27-steroid oxidoreductaseΔ5-isomerase activity of HSD3B1,an enzyme which is highly expressed in placenta. Proof-of-principle experiments confirmed that HSD3B1 has this activity. We speculate thatHSD3B1 in placenta is the source of the unexpected 3-oxo-4-ene oxysterols in cord and pregnant women’s plasma and may have a role in controlling the abundance of biologically active oxysterols delivered to the fetus. Journal Article Open Biology 13 5 The Royal Society 2046-2441 placenta, mass spectrometry, bile acid, pregnancy, HSD3B1, oxysterol 1 5 2023 2023-05-01 10.1098/rsob.220313 http://dx.doi.org/10.1098/rsob.220313 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) 2023-11-15T12:41:02.8708421 2022-10-21T09:46:59.5002597 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Alison Dickson 1 Eylan Yutuc 0000-0001-9971-1950 2 Cathy Thornton 0000-0002-5153-573X 3 James E. Dunford 0000-0002-9932-4042 4 Udo Oppermann 5 Yuqin Wang 0000-0002-3063-3066 6 William Griffiths 0000-0002-4129-6616 7 61629__27805__17987f2615a14b3eac84c8f5f4b7fd2f.pdf 61629.pdf 2023-06-12T14:24:36.9565555 Output 3685048 application/pdf Version of Record true 2023 The Authors. Published by the Royal Society under the terms of the Creative Commons AttributionLicense http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the originalauthor and source are credited. true eng http://creativecommons.org/licenses/by/4.0/ |
title |
HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta |
spellingShingle |
HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta Alison Dickson Eylan Yutuc Cathy Thornton Yuqin Wang William Griffiths |
title_short |
HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta |
title_full |
HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta |
title_fullStr |
HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta |
title_full_unstemmed |
HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta |
title_sort |
HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta |
author_id_str_mv |
82dc4360769527a5f3a0cd9d85cdff40 99332f073ce913a9b7d8b6441b17516d c71a7a4be7361094d046d312202bce0c c92729b58622f9fdf6a0e7d8f4ce5081 3316b1d1b524be1831790933eed1c26e |
author_id_fullname_str_mv |
82dc4360769527a5f3a0cd9d85cdff40_***_Alison Dickson 99332f073ce913a9b7d8b6441b17516d_***_Eylan Yutuc c71a7a4be7361094d046d312202bce0c_***_Cathy Thornton c92729b58622f9fdf6a0e7d8f4ce5081_***_Yuqin Wang 3316b1d1b524be1831790933eed1c26e_***_William Griffiths |
author |
Alison Dickson Eylan Yutuc Cathy Thornton Yuqin Wang William Griffiths |
author2 |
Alison Dickson Eylan Yutuc Cathy Thornton James E. Dunford Udo Oppermann Yuqin Wang William Griffiths |
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Open Biology |
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13 |
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2023 |
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Swansea University |
issn |
2046-2441 |
doi_str_mv |
10.1098/rsob.220313 |
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The Royal Society |
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Faculty of Medicine, Health and Life Sciences |
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facultyofmedicinehealthandlifesciences |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine |
url |
http://dx.doi.org/10.1098/rsob.220313 |
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description |
Most biologically active oxysterols have a 3β-hydroxy-5-ene function in thering system with an additional site of oxidation at C-7 or on the side-chain. In blood plasma oxysterols with a 7α-hydroxy group are also observed with the alternative 3-oxo-4-ene function in the ring system formed by ubiquitously expressed 3β-hydroxy-Δ5-C27-steroid oxidoreduc-taseΔ5-isomerase, HSD3B7. However, oxysterols without a 7α-hydroxy group are not substrates for HSD3B7 and are not usually observed with the 3-oxo-4-ene function. Here we report the unexpected identification of oxysterols in plasma derived from umbilical cord blood and blood from pregnant women taken before delivery at 37+ weeks of gestation, of side-chain oxysterols with a 3-oxo-4-ene function but no 7α-hydroxy group.These 3-oxo-4-ene oxysterols were also identified in placenta, leading to the hypothesis that they may be formed by a previously unrecognized 3β-hydroxy-Δ5-C27-steroid oxidoreductaseΔ5-isomerase activity of HSD3B1,an enzyme which is highly expressed in placenta. Proof-of-principle experiments confirmed that HSD3B1 has this activity. We speculate thatHSD3B1 in placenta is the source of the unexpected 3-oxo-4-ene oxysterols in cord and pregnant women’s plasma and may have a role in controlling the abundance of biologically active oxysterols delivered to the fetus. |
published_date |
2023-05-01T20:16:34Z |
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11.04748 |