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

点击翻译按钮获取中文摘要

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 found that Drosophila contain two selenocysteine isoacceptors, the levels of which are not changed during development. The gene for these isoacceptors maps to a single locus on chromosome 2 at regions 47 E or F. Further, we have found that the selenocysteine tRNA population contains at least two additional isoacceptors which are vastly enriched in muscle tissues of selenium deficient rats. Resupplementation of selenium deficient rats with this element shows an enhancement in the selenocysteine tRNA population and alteration in the distribution of the selenocysteine isoacceptors. The rate of change varies, however, in different tissues (e.g., the distribution of isoaccep-tors in liver returns to that in selenium adequate rats at 24-48 hours while that in muscle was still incom-plete at 72 hours). Most of the molecular changes in primary structure of selenocysteine tRNAs that occur in response to selenium are being examined in Xenopus oocytes where the kinetics of synthesis of modified bases in tRNA have been determined in detail. Transcription of selenocysteine tRNA in HeLa cell and Xenopus oocyte extracts that are supplemented with mutant TATA box binding proteins show that common surfaces of the TATA box binding protein are used for transcribing this gene and Pol II transcribed genes even though this tRNA is expressed by Pol III.