Effect of selenium on rat thioredoxin reductase activity: increase by supranutritional selenium and decrease by selenium deficiency.
Thioredoxin reductase is a newly identified selenocysteine-containing enzyme that catalyzes the NADPH-dependent reduction of the redox protein thioredoxin. Thioredoxin stimulates cell growth, is found in dividing normal cells, and is over-expressed in a number of human cancers. Redox activity is essential for the growth effects of thioredoxin; thus, thioredoxin reductase could be involved in regulating cell growth through its reduction of thioredoxin. In rats fed a selenium-deficient diet (<0.01 ppm) for up to 98 days, thioredoxin reductase activity was decreased, compared with that of rats fed a normal selenium diet (0.1 ppm), in lung, liver, and kidney, while thioredoxin reductase activity in the spleen and prostate was unaltered. Rats fed a high selenium diet (1.0 ppm) exhibited a 1.5-fold increase in kidney and a 2.0-fold increase in lung thioredoxin reductase activity that began to return to control values after 20 and 69 days, respectively. Liver showed a 2.1-fold increase in thioredoxin reductase activity at 20 days only. Thioredoxin reductase protein levels measured by western blotting using an antibody to human thioredoxin reductase were decreased in rats fed the selenium-deficient diet and did not increase in rats fed the high selenium diet. Rat thioredoxin reductase was shown to incorporate 75Selenium. Thus, in some tissues at least, the increase in thioredoxin reductase activity of rats fed a high selenium diet appears to be due to an increase in the specific activity of the enzyme, possibly caused by increased selenocysteine incorporation without an increase in thioredoxin reductase protein synthesis.
Berggren
M M
MM
Arizona Cancer Center, University of Arizona, Tucson 85724-5024, USA.
Mangin
J F
JF
Gasdaka
J R
JR
Powis
G
G
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018890:Chemoprevention; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D009369:Neoplasms / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000097:blood / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000187:drug effects* / Q000378:metabolism
D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium