Se is an essential nutrient, and Se deficiency is an etiologic factor in a cardiomyopathy which occurs in Chinese children. Other diseases, including cancer, may be affected by the Se status of the population. Se is an essential constituent of glutathinone peroxidase, but it has effects which cannot be explained by this enzyme. These include its effect on a number of xenobiotic-metabolizing enzymes, heme metabolism and diquat-induced lipid peroxidaton. This proposal will attempt to elucidate some of the metabolic functions of Se which are responsible for its nutritional effects. A rat plasma selenoprotein, designated 75Se-P, has been identified and is being purified. It will be characterized and studied to determine if it is related to any of the known metabolic functions of Se. A radioimmunoassay will be developed for 75Se-P. This will be used to measure plasma 75Se-P levels under various conditions of Se supply. Attempts will be made to correlate 75Se-P level with Se effect. Uptake of 75Se-P by various organs will be studied. A GSH-dependent rat liver microsomal free radical-scavenging mechanism has been described. It blocks attack by CC14-derived free radicals on the microsomal membrane under aerobic conditions. This mechanism will be characterized in vitro. A potential product of the scavenging of 14CC14-derived radicals has been detected. This product will be purified using ion exchange and HPLC, and identified with the aim of learning the mechanism of the scavenging. Hyperbaric 02 lessens CC14 toxicity in rats and may act by increasing liver 02 tension which allows radical scavenging by the GSH-dependent mechanism. This will be studied in hyperbaric chambers which allow measurement of exhaled CHC13, CC14, and ethane by gas chromatography. Liver GSH synthesis and release into the plasma is twice as great in Se-deficient rats as in controls. The effect of Se underlying this is not known. A number of products of GSH breakdown will be tested for activity in diminishing GSH release by Se-deficient liver: GSH is removed from plasma by the kidney. Extraction is less efficient by the Se-deficient kidney than by the control. Perfused kidneys from Se-deficient and from, control rats will be studied to earn whether Se deficiency affects GSH release and GSH extraction. The maximum uptake capacity will be determined. These studies should increase knowledge of the metabolic function of Se. They may provide insight into its role in human disease states.
Showing the most recent 10 out of 99 publications
