title: Thioredoxin reductase activity in rat liver is not affected by supranutritional levels of monomethylated selenium in vivo and is inhibited only by high levels of selenium in vitro.
abstract: Thioredoxin reductase is a selenoenzyme responsible for maintaining thioredoxin in the reduced form. Because thioredoxin is involved in many cellular processes, thioredoxin reductase is likely to be an important regulatory protein for both normal and transformed cells. Monomethylated selenium compounds inhibit carcinogenesis. In the present study, we investigated whether methylated forms of selenium would alter thioredoxin reductase activity in rats. The liver enzyme was used as a model system. Se-methylselenocysteine and methylseleninic acid consumed by rats at 2 microg Se/g diet for 3, 6, 10 or 22 wk did not affect activity compared with a basal diet containing 0.1 microg Se/g. The direct addition of 50 micromol dimethyl diselenide or dimethyl selenenylsulfide per L to liver extracts significantly inhibited thioredoxin reductase activity by approximately 60%. The magnitude of inhibition was dependent on the amount of thioredoxin in the assay and was reversible by dialysis, suggesting that a competitive type of inhibition occurs in vitro. Although thioredoxin reductase can be inhibited by high levels of selenium in a cell-free system, it should be noted that such a condition is unlikely to be attainable in vivo. Caution needs to be exercised in interpreting the in vitro results.
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin, Madison, Madison, Wisconsin 53706, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ganther
authors.forename: C
authors.initials: C
authors.lastname: Ip
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008745:Methylation; D009752:Nutritional Status; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000378:metabolism / Q000494:pharmacology*; D018036:Selenium Compounds / Q000378:metabolism / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018036:Selenium Compounds; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium