SELENIUM REGULATION OF THE GLUTATHIONE PEROXIDASE GENE

硒对谷胱甘肽过氧化物酶基因的调节

• 批准号: 3463855
• 负责人: MERRILL CHRISTENSEN
• 金额: $ 9.74万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3463855
• 关键词: RNA splicing; binding proteins; dietary trace element; gene expression; glutathione peroxidase; laboratory rat; liver metabolism; messenger RNA; metal metabolism disorder; metalloenzyme; metalloproteins; methylation; nuclear runoff assay; nutrition related tag; radiotracer; selenium; transcription factor

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.

营养素摄入改变基因的机制探讨 表达可能揭示饮食因素改变的方式 对癌症易感性。这项工作将研究表达式和 肝脏硒酶谷胱甘肽过氧化物酶基因的调控 (GSH：过氧化氢氧化还原酶，EC 1.11.19)(GSH-Px)。依赖于这一点 将确定对膳食中硒(Se)摄入量的规定。 这需要与世隔绝、结构性和组织性 大鼠肝脏谷胱甘肽过氧化物酶基因的特性依赖于 对饮食的转录或翻译调节将由 比较GSH-PX mRNA的径流转录、积累和稳定性， 和抗GSH-Px抗体反应蛋白的蓄积和稳定性 从喂食低硒或适硒饲料的大鼠的肝脏中提取。这些 实验将显示GSH-Px基因表达中的哪些反应 对膳食中的硒摄入量最为敏感。 研究膳食中SE摄入量调节表达的一种机制 对GSH-Px基因进行了电泳迁移率改变(EMS)分析和 将进行甲基化干扰分析。这些实验将 展示反式作用因子(蛋白质)与序列的结合 GSH-Px基因的侧翼区。用杠杆核进行的分析 从硒充足和缺硒动物中提取的物质将证明 潜在调节蛋白对膳食硒摄入量的依赖性。它的用途 注射75Se的大鼠肝脏核提取液的含量 将显示硒蛋白本身，或硒结合蛋白， 由膳食Se摄入量诱导，在GSH-Px的调节中发挥作用 吉恩。