ROLE OF SELENIUM IN PREVENTING CANCER, HEART DISEASE AND DELAYING AGING PROCESS

硒是哺乳动物饮食中的必需元素， 或者在饮食中过多的摄入， 对健康的影响硒具有预防心脏病的作用， 与预防癌症和延缓衰老有关 过程这一因素发挥其影响，部分是通过它的存在， 硒蛋白中的氨基酸硒代半胱氨酸。因此，我们 关注于硒代半胱氨酸在tRNA上生物合成的方式 并被整合到蛋白质中。在过去的一年里，我们使用 靶向载体以去除一个拷贝的硒代半胱氨酸tRNA基因 小鼠胚胎干细胞的基因组。硒代半胱氨酸tRNA 在这些细胞中，细胞数量减少了约50%，但 硒蛋白的生物合成显然不受影响，这表明， 硒代半胱氨酸转运蛋白的水平不受蛋白质 合成.基因敲除小鼠是从小鼠胚胎发育而来的 缺乏tRNA基因的干细胞，以检查缺乏tRNA基因的影响。 这个基因在老鼠身上。我们也在制造额外拷贝的转基因小鼠 研究硒代半胱氨酸tRNA基因的影响， 富集的硒代半胱氨酸tRNA群体对蛋白质合成的影响。我们有 完成了对硒代半胱氨酸tRNA群体的分析研究 在补充硒的缺硒大鼠中。 后一项研究表明，硒代半胱氨酸转运RNA的富集 在硒的存在下， 出现相应的同位素受体，富集率和 变化依赖于组织。一种新的硒蛋白，分子量为15kDa 蛋白质，是由我们的一位成员发现和部分纯化的。 实验室在他来之前。自从他到来以来，15 kDa 蛋白质已经被测序，它已经被定位在人类染色体上 1和证据表明，它可能涉及的进展， 癌此外，大量的硒代半胱氨酸tRNA 已制备了丝氨酸tRNA的异源受体和分析晶体 这些分子与丝氨酰-tRNA合成酶复合。丝氨酰转移核糖核酸 合成酶氨酰化硒代半胱氨酸和丝氨酸tRNA。 果蝇硒代半胱氨酸转运蛋白被大量分离， 它们的主要序列被确定。这些tRNA与 相应的基因。分析了硒代半胱氨酸tRNA群体， 牛的肝脏和睾丸以及中国仓鼠的肝脏和卵巢 这些同种受体在聚丙烯酰胺凝胶上的迁移方式不同， 肝脏和睾丸以及中国仓鼠的肝脏和卵巢中，表明 不同的物种可能是通过编辑而产生的。我们正在进一步 调查这种可能性。这个基因的转录揭示了 一种参与含有TATA的Pol III基因表达的新因子 盒子

Selenium is an essential element in the diet of mammals and too little or too much in the diet within a narrow range can have devastating effects on health. Selenium has a role in preventing heart disease and has been implicated in preventing cancer and in delaying the aging process. This element exerts its effects, in part, through its presence in selenoproteins as the amino acid, selenocysteine. We, therefore, are focusing on the means by which selenocysteine is biosynthesized on tRNA and is incorporated into protein. In the past year, we have used targeting vectors to remove one copy of the selenocysteine tRNA gene from the genome of mouse embryonic stem cells. The selenocysteine tRNA population is reduced approximately 50% in these cells, but the biosynthesis of selenoproteins apparently is unaffected suggesting that the levels of the selenocysteine tRNAs are not limiting in protein synthesis. Knockout mice are being developed from the mouse embryonic stem cells lacking the tRNA gene to examine the effects of the loss of this gene on mice. We are also making transgenic mice with extra copies of the selenocysteine tRNA gene in their genome to study the effects of an enriched selenocysteine tRNA population on protein synthesis. We have completed a study on an analysis of the selenocysteine tRNA population in selenium deficient rats which have been resupplemented with selenium. The latter studies show that an enrichment of the selenocysteine tRNAs in the presence of selenium and an alteration in the distribution of the corresponding isoacceptors occurs and that the rate of enrichment and change is tissue dependent. A new selenoprotein, designated as 15 kDa protein, was discovered and partially purified by one member of our laboratory prior to his coming here. Since his arrival, the 15 kDa protein has been sequenced, it has been localized on human chromosome 1 and evidence suggests that it may be involved in the progression of cancer. In addition, large quantities of the selenocysteine tRNA isoacceptors and of serine tRNA have been prepared to analyze crystals of these molecules complexed with seryl-tRNA synthetase. Seryl-tRNA synthetase aminoacylates both selenocysteine and serine tRNAs. Drosophila selenocysteine tRNAs were isolated in large quantities and their primary sequences determined. These tRNAs are co-linear with the corresponding gene. Analysis of the selenocysteine tRNA population in bovine liver and testis and Chinese hamster liver and ovaries have shown that these isoacceptors migrate differently on polyacrylamide gels in liver and testis and in Chinese hamster liver and ovaries suggesting that the different species may arise by editing. We are further investigating this possibility. Transcription of this gene has revealed a new factor involved in expression of Pol III genes containing a TATA box.