Sterols and oxysterols in plasma from Smith-Lemli-Opitz syndrome patients.
Sterols and oxysterols in plasma from Smith-Lemli-Opitz syndrome patients.
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DOI：
10.1016/j.jsbmb.2016.03.018
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发表时间：
2017-05
影响因子：
4.1
通讯作者：
Wang, Yuqin
中科院分区：
文献类型：
--
作者：
Griffiths, William J.;Abdel-Khalik, Jonas;Crick, Peter J.;Ogundare, Michael;Shackleton, Cedric H.;Tuschl, Karin;Kwok, Mei Kwun;Bigger, Brian W.;Morris, Andrew A.;Honda, Akira;Xu, Libin;Porter, Ned A.;Bjorkhem, Ingemar;Clayton, Peter T.;Wang, Yuqin
关键词：
Smith-Lemli-Opitz综合征（SLOS）是一种严重的常染色体隐性遗传病，由胆固醇合成酶7-脱氢胆固醇还原酶（Δ7-sterol还原酶，DHCR7, EC 1.3.1.21）缺陷导致胆固醇前体7-脱氢胆固醇（7-DHC）在组织和血浆中的积累引起。虽然与SLOS相关的潜在酶缺乏是明确的，但可能有多种机制导致SLOS病理。为了进一步了解SLOS的病因，我们分析了SLOS患者的血浆，寻找可能导致某些病理的7-DHC代谢物。我们鉴定了一种新的羟基-8-脱氢胆固醇，它是24-或25-羟基-8-脱氢胆固醇，以及已知的代谢产物26-羟基-8-脱氢胆固醇，4-羟基-7-脱氢胆固醇，3β，5α-二羟基胆固醇-7-en-6- 1和7α，8α-环氧胆固醇。这些代谢物在对照血浆中均未检测到可量化水平（0.5 ng/mL）。
Smith-Lemli-Opitz syndrome (SLOS) is a severe autosomal recessive disorder resulting from defects in the cholesterol synthesising enzyme 7-dehydrocholesterol reductase (Δ7-sterol reductase, DHCR7, EC 1.3.1.21) leading to a build-up of the cholesterol precursor 7-dehydrocholesterol (7-DHC) in tissues and blood plasma. Although the underling enzyme deficiency associated with SLOS is clear there are likely to be multiple mechanisms responsible for SLOS pathology. In an effort to learn more of the aetiology of SLOS we have analysed plasma from SLOS patients to search for metabolites derived from 7-DHC which may be responsible for some of the pathology. We have identified a novel hydroxy-8-dehydrocholesterol, which is either 24- or 25-hydroxy-8-dehydrocholesterol and also the known metabolites 26-hydroxy-8-dehydrocholesterol, 4-hydroxy-7-dehydrocholesterol, 3β,5α-dihydroxycholest-7-en-6-one and 7α,8α-epoxycholesterol. None of these metabolites are detected in control plasma at quantifiable levels (0.5 ng/mL).
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影响因子：
9.3
作者：
Griffiths, William J.;Wang, Yuqin;Karu, Kersti;Samuel, Emmanuel;McDonnell, Shane;Hornshaw, Martin;Shackleton, Cedric
通讯作者：
Shackleton, Cedric
影响因子：
4.2
作者：
Paglia, Giuseppe;D'Apolito, Oceania;Corso, Gaetano
通讯作者：
Corso, Gaetano
影响因子：
5.8
作者：
Mazein, Alexander;Watterson, Steven;Hsieh, Wei-Yuan;Griffiths, William J.;Ghazal, Peter
通讯作者：
Ghazal, Peter
影响因子：
6.5
作者：
Korade, Zeljka;Xu, Libin;Porter, Ned A.
通讯作者：
Porter, Ned A.
影响因子：
5.8
作者：
Meljon, Anna;Watson, Gordon L.;Wang, Yuqin;Shackleton, Cedric H. L.;Griffiths, William J.
通讯作者：
Griffiths, William J.