24S,25-Epoxycholesterol in mouse and rat brain.
24S,25-Epoxycholesterol in mouse and rat brain.
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DOI：
10.1016/j.bbrc.2014.05.012
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发表时间：
2014-06-27
影响因子：
3.1
通讯作者：
Griffiths, William J.
中科院分区：
文献类型：
--
作者：
Wang, Yuchen;Karu, Kersti;Meljon, Anna;Turton, John;Yau, Joyce L.;Seckl, Jonathan R.;Wang, Yuqin;Griffiths, William J.
关键词：
在啮齿动物脑中鉴别并定量24 S，25-环氧胆固醇。敲除Cyp 27 a1导致24 S，25-环氧胆固醇减少。敲除Cyp 7 b1导致24 S，25-环氧胆固醇增加。24 S，25-环氧胆固醇由Cyp 7 b1代谢，而不是Cyp 27 a1。24 S，25-环氧胆固醇在产生胆固醇的甲羟戊酸途径的分流中形成。它是已知最有效的肝脏X受体激活剂之一，可抑制固醇调节元件结合蛋白加工。直到最近，由于24 S，25-环氧胆固醇的热不稳定性和缺乏强发色团，一直无法以高灵敏度分析24 S，25-环氧胆固醇。本文报道了啮齿类动物脑中24 S，25-环氧胆固醇的分析结果，成年小鼠和大鼠脑中24 S，25-环氧胆固醇的含量为0.4-1.4 μg/g湿重。两种啮齿动物脑中24 S-羟基胆固醇含量为20 μg/g，而小鼠脑中胆固醇含量为10-20 mg/g。通过利用氧固醇7α-羟化酶（Cyp 7 b1）基因敲除小鼠，我们发现这种酶对24 S，25-环氧化物的后续代谢很重要。
24S,25-Epoxycholesterol identified and quantified in rodent brain. Knock out of Cyp27a1 leads to a decrease in 24S,25-epoxycholesterol. Knock out of Cyp7b1 leads to an increase in 24S,25-epoxycholesterol. 24S,25-Epoxycholesterol is metabolised by Cyp7b1 but not Cyp27a1. 24S,25-Epoxycholesterol is formed in a shunt of the mevalonate pathway that produces cholesterol. It is one of the most potent known activators of the liver X receptors and can inhibit sterol regulatory element-binding protein processing. Until recently analysis of 24S,25-epoxycholesterol at high sensitivity has been precluded by its thermal lability and lack of a strong chromophore. Here we report on the analysis of 24S,25-epoxycholesterol in rodent brain where its level was determined to be of the order of 0.4–1.4 μg/g wet weight in both adult mouse and rat. For comparison the level of 24S-hydroxycholesterol in brain of both rodents was of the order of 20 μg/g, while that of cholesterol in mouse was 10–20 mg/g. By exploiting knockout mice for the enzyme oxysterol 7α-hydroxylase (Cyp7b1) we show that this enzymes is important for the subsequent metabolism of the 24S,25-epoxide.
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影响因子：
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作者：
Wang Y;Sousa KM;Bodin K;Theofilopoulos S;Sacchetti P;Hornshaw M;Woffendin G;Karu K;Sjövall J;Arenas E;Griffiths WJ
通讯作者：
Griffiths WJ
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通讯作者：
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作者：
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通讯作者：
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