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首页> 外文期刊>The Journal of Nutritional Biochemistry >Alpha-tocopherol modulates genes involved in hepatic xenobiotic pathways in mice
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Alpha-tocopherol modulates genes involved in hepatic xenobiotic pathways in mice

机译：α-生育酚调节小鼠肝异源途径中涉及的基因

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摘要

Hepatic proteins involved in xenobiotic pathways (Phases I, II and III) are responsible for the metabolism and disposition of endogenous and exogenous compounds including dietary phytochemicals. To test the hypothesis that elevated l-tocopherol intakes alter gene expression of hepatic xenobiotic pathways, mice were fed diets supplemented with either 1000 IU (+E) or 35 IU (E) all-rac-l-tocopheryl acetate for 4 months; liver RNA was isolated, and gene expression was determined using both whole genome microarray and real-time quantitative polymerase chain reaction analyses. Hepatic l-tocopherol (173pl18 vs. 21pl1 nmol/g, meanplS.E.) and its metabolite (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman, 0.232pl0.046 vs. 0.031pl0.019 nmol/g) concentrations were approximately eightfold higher following the +E dietary treatment. In +E relative to E mice, gene expression of Phase I enzymes, P450 oxidoreductase and cytochrome P450 3a11 increased 1.6- and 4.0-fold, respectively; two Phase II genes, sulfotransferase 2a and glutathione S-transferase mu 3, increased 10.8- and 1.9-fold respectively, and a Phase III biliary transporter, Abcb1a, doubled. Thus, consumption of high-level dietary l-tocopherol simultaneously coordinated Phase I, II and III gene expression. These data demonstrate that increased hepatic l-tocopherol modulates its own concentrations through increasing xenobiotic metabolism, a process that may alter metabolism of other foreign compounds, such as therapeutic drugs and phytochemicals, in humans.
机译：涉及异种生物途径的肝蛋白（第I，II和III期）负责内源性和外源性化合物（包括膳食植物化学物质）的代谢和处置。为了检验增加的1-生育酚摄入量会改变肝异源生物途径基因表达的假说，给小鼠喂食了补充了1000 IU（+ E）或35 IU（E）全外消旋-1-生育酚乙酸酯的饮食，持续了4个月。分离肝RNA，并使用全基因组微阵列和实时定量聚合酶链反应分析确定基因表达。肝1-生育酚（173pl18 vs. 21pl1 nmol / g，meanplS.E。）及其代谢产物（2,5,7,8-四甲基-2-（2'-羧乙基）-6-羟基苯并二氢吡喃，0.232pl0.046 vs在+ E饮食治疗后，0.031pl0.019 nmol / g）的浓度大约高出八倍。在+ E小鼠中，相对于E小鼠，I期酶，P450氧化还原酶和细胞色素P450 3a11的基因表达分别增加了1.6倍和4.0倍。 II期的两个基因，磺基转移酶2a和谷胱甘肽S-转移酶mu 3，分别增加了10.8和1.9倍，而III期的胆汁转运蛋白Abcb1a增加了一倍。因此，高水平饮食中1-生育酚的消耗同时协调了I，II和III期基因表达。这些数据表明，增加的肝脏1-生育酚通过增加异种生物代谢来调节其自身浓度，该过程可能改变人体内其他外来化合物（例如治疗药物和植物化学物质）的代谢。

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