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

硒是哺乳动物饮食中的一种必需元素，含量太少。 或者在狭窄的范围内摄入过多的食物可能会产生毁灭性的影响 对健康的影响。硒具有预防心脏病和预防心脏病的作用 与预防癌症和延缓衰老有关 进程。这种元素的作用部分是通过它的存在来实现的 在硒蛋白质中，作为氨基酸的硒半胱氨酸。因此，我们是 重点介绍硒半胱氨酸在tRNA上的生物合成途径 并被结合到蛋白质中。在过去的一年里，我们使用了 靶向载体去除硒半胱氨酸tRNA基因的一个拷贝 来自小鼠胚胎干细胞的基因组。硒半胱氨酸tRNA 这些细胞中的种群减少了大约50%，但 硒蛋白的生物合成显然没有受到影响，这表明 硒半胱氨酸tRNAs的水平不受蛋白质的限制 综合。基因敲除小鼠是从小鼠胚胎发育而来的 缺乏tRNA基因的干细胞检测其丢失的效果 老鼠身上的这种基因。我们还在制造带有额外拷贝的转基因小鼠 对其基因组中的硒半胱氨酸tRNA基因的影响进行研究 富硒半胱氨酸tRNA群体对蛋白质合成的影响。我们有 完成了对硒半胱氨酸tRNA群体的分析研究 在补硒后的缺硒大鼠中。 后者的研究表明，硒半胱氨酸tRNAs的丰富 在有硒存在的情况下， 相应的同种异构体出现，并且富集率和 变化依赖于组织。一种新的硒蛋白，命名为15 kDa 蛋白质，是由我们的一位成员发现并部分纯化的 在他来这里之前的实验室里。自从他到达后，15 kDa 蛋白质已经被测序，它已经定位在人类染色体上 1有证据表明，它可能参与了 癌症。此外，大量的硒半胱氨酸tRNA 已经制备了丝氨酸trna的同工受体和trna来分析晶体。 其中，这些分子与丝氨酰-tRNA合成酶络合。丝氨酰-tRNA 合成酶氨基酰化硒半胱氨酸和丝氨酸tRNAs。 大量分离果蝇硒半胱氨酸tRNAs 它们的主要序列被确定。这些tRNA与 相应的基因。中国人群中硒半胱氨酸tRNA群体分析 牛的肝脏和睾丸以及中国仓鼠的肝脏和卵巢已经显示出 这些异构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 不同的物种可能会通过编辑而出现。我们走得更远了 调查这一可能性。这种基因的转录已经揭示了 含有TATA的POLIII基因表达的新因子 盒。

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.