24(S),25-Epoxycholesterol: A messenger for cholesterol homeostasis
24(S),25-Epoxycholesterol: A messenger for cholesterol homeostasis
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DOI：
10.1016/j.biocel.2008.05.029
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发表时间：
2009-04-01
影响因子：
4
通讯作者：
Brown, Andrew J.
中科院分区：
文献类型：
--
作者：
Brown, Andrew J.
氧甾醇 24(S),25-环氧胆固醇是在所有胆固醇生成细胞中胆固醇生物合成途径的分流中产生的。越来越多的证据表明，内源性 24(S),25-环氧胆固醇可以在多个水平上发挥作用，以控制急性胆固醇稳态。例如，这种氧甾醇可抑制胆固醇稳态的主要调节因子（甾醇调节元件结合蛋白）的激活。事实上，24(S),25-环氧胆固醇似乎可以作为胆固醇合成的衡量标准，并防止这种潜在细胞毒性分子的产生激增。此外，内源性 24(S),25-环氧胆固醇是肝脏 X 受体的天然配体，可诱导胆固醇流出相关基因的表达。通过部分抑制氧化角鲨烯环化酶催化的分流开始后的步骤，可以人为地升高内源性 24(S),25-环氧胆固醇的水平。操纵自我调节途径来产生生理调节剂的想法很有吸引力，值得进一步评估，这种调节剂可以增强胆固醇的去除并减少摄取和合成。 (C) 2008 Elsevier Ltd. 保留所有权利。
The oxysterol 24(S),25-epoxycholesterol is made in a shunt in the cholesterol biosynthetic pathway in all cholesterogenic cells. Evidence is emerging that endogenous 24(S),25-epoxycholesterol can work at several levels to control acute cholesterol homeostasis. For instance, this oxysterol suppresses activation of the master regulators of cholesterol homeostasis, the sterol regulatory element binding proteins. Indeed, 24(S),25-epoxycholesterol appears to serve as a measure of cholesterol synthesis and to protect against surges in the production of this potentially cytotoxic molecule. In addition, endogenous 24(S),25-epoxycholesterol is a natural ligand for the liver X receptors which induce expression of cholesterol efflux-related genes. Levels of endogenous 24(S),25-epoxycholesterol can be artificially elevated by partially inhibiting the step after the start of the shunt, catalysed by oxidosqualene cyclase. The idea of manipulating a self-governing pathway for the production of a physiological regulator, that can enhance cholesterol removal and decrease uptake and synthesis, is attractive and warrants further evaluation. (C) 2008 Elsevier Ltd. All rights reserved.