Cholesterol metabolites exported from human brain.
Cholesterol metabolites exported from human brain.
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DOI：
10.1016/j.steroids.2015.01.026
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发表时间：
2015-07
期刊：
影响因子：
2.7
通讯作者：
Griffiths WJ
中科院分区：
文献类型：
--
作者：
Iuliano L;Crick PJ;Zerbinati C;Tritapepe L;Abdel-Khalik J;Poirot M;Wang Y;Griffiths WJ
测量了20多种固醇进出人脑的流量。经证实，24 S-羟基胆固醇以约2-3 mg/24 h从脑中输出。从大脑输出的其他固醇包括5α-羟基-6-氧代-、7β-羟基-和7-氧代-胆固醇。人类大脑含有约25%的人体胆固醇。脑通过血脑屏障与血液循环分离。虽然胆固醇不会通过这个屏障，但胆固醇的氧化形式可以穿过屏障。在这里，通过测量颈静脉和前臂静脉中血浆中氧固醇含量的差异，通过质谱法（MS），我们能够确定大脑和循环之间的20多种胆固醇代谢物的通量。我们证实，24 S-羟基胆固醇从脑中输出的速率约为2-3 mg/24 h。气相色谱（GC）-MS数据显示，胆固醇代谢物5α-羟基-6-氧代胆固醇（3β，5 α-二羟基胆甾烷-6-酮）、7β-羟基胆固醇和7-氧代胆固醇（通常认为是通过活性氧形成的）从脑中的输出速率相似，分别约为0.1、2和2 mg/24 h。虽然没有统计学意义，但GC-MS和液相色谱（LC）-MS方法均表明（25 R）26-羟基胆固醇输入脑，而LC-MS表明7α-羟基-3-氧代胆甾-4-烯酸从脑输出。
Flux of more than 20 sterols into and out from human brain measured. 24S-hydroxycholesterol confirmed to be exported from brain at about 2–3 mg/24 h. Other sterols exported from brain include 5α-hydroxy-6-oxo-, 7β-hydroxy- and 7-oxo-cholesterol. The human brain contains approximately 25% of the body’s cholesterol. The brain is separated from the circulation by the blood brain barrier. While cholesterol will not passes this barrier, oxygenated forms of cholesterol can cross the barrier. Here by measuring the difference in the oxysterol content of blood plasma in the jugular vein and in a forearm vein by mass spectrometry (MS) we were able to determine the flux of more than 20 cholesterol metabolites between brain and the circulation. We confirm that 24S-hydroxycholesterol is exported from brain at a rate of about 2–3 mg/24 h. Gas chromatography (GC)–MS data shows that the cholesterol metabolites 5α-hydroxy-6-oxocholesterol (3β,5α-dihydroxycholestan-6-one), 7β-hydroxycholesterol and 7-oxocholesterol, generally considered to be formed through reactive oxygen species, are similarly exported from brain at rates of about 0.1, 2 and 2 mg/24 h, respectively. Although not to statistical significance both GC–MS and liquid chromatography (LC)–MS methods indicate that (25R)26-hydroxycholesterol is imported to brain, while LC–MS indicates that 7α-hydroxy-3-oxocholest-4-enoic acid is exported from brain.