Crossing the barrier:: net flux of 27-hydroxycholesterol into the human brain
Crossing the barrier:: net flux of 27-hydroxycholesterol into the human brain
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DOI：
10.1194/jlr.m500024-jlr200
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发表时间：
2005-05-01
影响因子：
6.5
通讯作者：
Björkhem, I
中科院分区：
文献类型：
--
作者：
Heverin, M;Meaney, S;Björkhem, I
侧链氧化的氧固醇具有独特的穿过亲脂性膜的能力。我们使用从健康男性志愿者的颈内静脉和动脉采集的血浆样本检验了27-羟基胆固醇从循环到大脑的净流量这一假设。进行了两项独立的研究，一项是测量27-羟基胆固醇的总水平，另一项是测量27-羟基胆固醇的游离部分。在研究的大多数受试者中，动脉中的27-羟基胆固醇水平高于静脉，从循环中摄取的计算值约为5 mg/24 h。发现人脑中27-羟基胆固醇的分布与脑外起源一致，具有从白色到灰质的浓度梯度-与仅在脑中形成的24 S-羟基胆固醇相反的情况。鉴于血脑屏障对胆固醇是不可渗透的，并且27-羟基胆固醇是几种胆固醇敏感基因的有效调节剂，27-羟基胆固醇流入脑中可能是脑内和脑外胆固醇稳态之间的重要联系。
Side chain oxidized oxysterols have a unique ability to traverse lipophilic membranes. We tested the hypothesis that there is a net flux of 27-hydroxycholesterol from the circulation into the brain using plasma samples collected from the internal jugular vein and an artery of healthy male volunteers. Two independent studies were performed, one in which total levels of 27-hydroxycholesterol were measured and one in which the free fraction of 27-hydroxycholesterol was measured. In the majority of subjects studied, the level of 27-hydroxycholesterol was higher in the artery than in the vein, and uptake from the circulation was calculated to be about 5 mg/24 h. The distribution of 27-hydroxycholesterol in human brain was found to be consistent with an extracerebral origin, with a concentration gradient from the white to the gray matter - a situation opposite that of 24S-hydroxycholesterol, which is exclusively formed in brain. In view of the fact that the blood - brain barrier is impermeable to cholesterol and that 27-hydroxycholesterol is a potent regulator of several cholesterol-sensitive genes, the flux of 27-hydroxycholesterol into the brain may be an important link between intra- and extracerebral cholesterol homeostasis.