Vitamin E, nuclear receptors and xenobiotic metabolism
Vitamin E, nuclear receptors and xenobiotic metabolism
复制标题
DOI：
10.1016/j.abb.2003.10.009
复制
发表时间：
2004-03-01
影响因子：
3.9
通讯作者：
Traber, MG
中科院分区：
文献类型：
--
作者：
Traber, MG
在美国，超过3500万人每天服用补充维生素E （α -生育酚）。在吸收和肝脏吸收之后，维生素E的命运在很大程度上是未知的。最近的临床研究报告了维生素E的副作用，这可能与它的肝脏代谢直接相关。在体外系统中，维生素E和利福平（一种已知的异种代谢刺激剂）都激活了妊娠X受体（PXR），这是一种孤儿核受体。PXR作为一种异源二聚体，与类视黄醇X受体（RXR）结合在基因启动子区域的特定顺式元件上。PXR/RXR调控一系列参与外源解毒的基因，包括氧化、偶联和转运蛋白。重要的是，PXR/RXR调节细胞色素P450 (CYP), CYP3A，参与超过50%的处方药的肝脏解毒。维生素E作为PXR配体可以改变PXR介导的这些反应。不幸的是，维生素E的药理学剂量在体内调节这些途径的程度尚未确定。(C) 2003 Elsevier Inc.版权所有。
Supplemental vitamin E (alpha-tocopherol) is taken daily by more than 35 million people in the US. Following absorption and liver uptake, the fate of vitamin E is largely unknown. Of potential importance are recent clinical studies that have reported adverse effects of vitamin E that may be directly related to its hepatic metabolism. In an in vitro system, both vitamin E and rifampicin, a known stimulator of xenobiotic metabolism, activated the pregnane X receptor (PXR), an orphan nuclear receptor. PXR as a heterodimer with the retinoid X receptor (RXR), binds to specific cis-elements in the promoter regions of genes. PXR/RXR regulates a constellation of genes involved in xenobiotic detoxification, including oxidation, conjugation, and transporters. Importantly, PXR/RXR regulates the cytochrome P450 (CYP), CYP3A, involved in the hepatic detoxification of more than 50% of prescription drugs. Vitamin E acting as a PXR ligand could alter these PXR-mediated reactions. Unfortunately, the extent to which pharmacologic doses of vitamin E modulate these pathways in vivo has not been determined. (C) 2003 Elsevier Inc. All rights reserved.