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SELENIUM REGULATION OF THE GLUTATHIONE PEROXIDASE GENE

硒对谷胱甘肽过氧化物酶基因的调节

基本信息

批准号：
2141850
负责人：
MERRILL CHRISTENSEN
金额：
$ 10.19万
依托单位：
BRIGHAM YOUNG UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-04-01 至 1995-12-31
项目状态：
已结题

项目摘要

Exploration of the mechanisms by which nutrient intake modifies gene expression may reveal the mean by which dietary factors can alter susceptibility to cancer. This work will examine the expression and regulation of the gene for the liver selenoenzyme glutathione peroxidase (GSH:H2O2 oxidoreductase, EC 1.11.19) (GSH-Px). Dependence of that regulation on dietary intake of selenium (Se) will be determined. This requires the isolation and structural and organizational characterization of the rat liver GSH-Px gene. Dependence of transcriptional or translational regulation on diet will be examined by comparing run-off transcripts, accumulation and stability of GSH-Px mRNA, and accumulation and stability of anti-GSH-Px antibody-reactive protein from livers of rats fed Se-deficient or Se-adequate diets. These experiments will show which reactions in the expression of the GSH-Px gene are most sensitive to dietary Se intake. To examine one mechanism by which dietary SE intake may regulate expression of the GSH-Px gene, electrophoretic mobility shift (EMS) assays and methylation interference assays will be done. These experiments will demonstrate binding of trans acting factors (proteins) to sequences in the flanking regions of the GSH-Px gene. Assays performed with lever nuclear extracts from se-adequate and Se-deficient animals will demonstrate the dependence of potential regulatory proteins on dietary Se intake. The use of nuclear extracts in these assays from livers of rats injected with 75 Se will show whether or not selenoproteins themselves, or Se-binding proteins, inducible by dietary Se intake, play a role in the regulation of the GSH-Px gene.

营养素摄入对基因调控机制的探讨表达可能揭示饮食因素可以改变对癌症的易感性。这项工作将检查表达式和肝硒酶谷胱甘肽过氧化物酶基因的调节 (GSH：H2 O2氧化还原酶，EC 1.11.19）（GSH-Px）。依赖于此将确定硒（Se）的膳食摄入量的调节。这就需要隔离，大鼠肝脏GSH-Px基因的特征。依赖性转录或翻译调控饮食将检查比较GSH-Px mRNA的流出转录、积累和稳定性，抗GSH-Px抗体反应蛋白的积累和稳定性从大鼠肝脏喂养硒缺乏或硒充足的饮食。这些实验将显示GSH-Px基因表达中的哪些反应对膳食硒摄入量最敏感。研究膳食SE摄入可能调节表达的一种机制， GSH-Px基因，电泳迁移率变动（EMS）测定和将进行甲基化干扰测定。这些实验将证明反式作用因子（蛋白质）与蛋白质中的序列结合 GSH-Px基因的侧翼区。用杠杆核进行的试验硒充足和硒缺乏动物的提取物将证明潜在调节蛋白对膳食硒摄入量的依赖性。使用在这些试验中，从注射75 Se的大鼠肝脏中提取核提取物将显示硒蛋白本身，或硒结合蛋白，硒诱导的GSH-Px活性，在GSH-Px的调节中发挥作用基因