Effect of selenium deficiency on type I 5'-deiodinase.
The type I iodothyronine 5'-deiodinase (5'-DI) present in rat liver and kidney has recently been demonstrated to be a selenoprotein. The goal of the present study was to examine in detail the effect of selenium (Se) deficiency on 5'-DI at the protein and mRNA levels. In weanling rats fed a selenium-deficient (Se(-)) diet for 6 weeks, 5'-DI activity was decreased 91 and 69% relative to control activities in liver and kidney, respectively. Administration of 3,5,3'-triiodothyronine resulted in a 2-fold increase in 5'-DI activity in control animals, but had little or no effect on 5'-DI activity in Se(-) animals. Western analysis using a specific antiserum directed against a bacterial fusion protein containing the carboxyl-terminal half of the 5'-DI protein demonstrated that this decrease in 5'-DI activity in Se(-) animals was explained by a marked decrease in 5'-DI protein. Administration of Se to Se(-) animals resulted in parallel increases in 5'-DI protein and activity over a 72-h time period. It was also shown that selenium deficiency was accompanied by a 40% decrease in 5'-DI mRNA levels in the kidney, but not in the liver. In both tissues, the administration of 3,5,3'-triiodothyronine resulted in increased 5'-DI mRNA levels which were not altered by selenium status. These studies indicate that selenium deficiency decreases 5'-DI activity by decreasing the amount of 5'-DI protein. The mechanism of this impairment in enzyme synthesis appears to be a defect in translation, presumably due to a block in the UGA-directed selenocysteine incorporation in selenium deficiency.
DePalo
D
D
Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756.
Kinlaw
W B
WB
Zhao
C
C
Engelberg-Kulka
H
H
St Germain
D L
DL
D000818:Animals; D001483:Base Sequence; D004032:Diet; D004926:Escherichia coli / Q000235:genetics; D006980:Hyperthyroidism / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008667:Metalloproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000276:immunology; D012643:Selenium / Q000172:deficiency*; D014284:Triiodothyronine / Q000378:metabolism; D014886:Weaning
D008667:Metalloproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014284:Triiodothyronine; D007453:Iodide Peroxidase; D012643:Selenium