Impairment of the selenoenzyme type I iodothyronine deiodinase in C3H/He mice.
Type I iodothyronine deiodinase (ID-I) activity is impaired in C3H/He (C3H) mice compared with BALB/c and C57BL/6N (C57) mice. In this study we compared ID-I activity and protein labeling with N-bromoacetyl(-)[125I]T3 (BrAc[125I]T3) or 75Se in liver microsomes of C3H and C57 mice. Hepatic ID-I activity in C3H mice was highly variable with a median of only 18% of that in C57 mice. However, C3H mice had normal serum T4 and T3 levels, although serum reverse T3 was increased. The 28-kilodalton (kDa) ID-I protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of BrAc[125I]T3-labeled microsomes. Labeling of this protein was virtually undetectable in C3H samples with low enzyme activity. ID-I activity in liver microsomes was strongly decreased in Se-deficient mice, which was paralleled by a drastic decrease in BrAc[125I]T3-labeling of the 28-kDa band compared with control mice. Labeling of ID-I with 75Se was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of liver microsomes of [75Se]selenite-injected mice. 75Se labeling of the 28-kDa band was markedly higher in Se-deficient than in control mice and was also markedly higher in C57 than in C3H mice. Finally, liver ID-I messenger RNA (mRNA) was measured on Northern blots using a rat ID-I complementary DNA probe. Messenger RNA levels correlated strongly with ID-I activity, showing a significant decrease in C3H mice. We conclude that in mice, like in rats and humans, ID-I is a selenoprotein. ID-I activity is impaired in C3H mice because of decreased transcription of the ID-I gene or reduced stability of the mRNA.
Schoenmakers
C H
CH
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
Pigmans
I G
IG
Poland
A
A
Visser
T J
TJ
D000818:Animals; D015152:Blotting, Northern; D015342:DNA Probes; D004591:Electrophoresis, Polyacrylamide Gel; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D012643:Selenium / Q000172:deficiency; D012644:Selenium Radioisotopes; D013045:Species Specificity; D014284:Triiodothyronine / Q000031:analogs & derivatives / Q000378:metabolism
D015342:DNA Probes; D012333:RNA, Messenger; D012644:Selenium Radioisotopes; D014284:Triiodothyronine; C036219:N-bromoacetyl-3,3',5-triiodothyronine; D007453:Iodide Peroxidase; D012643:Selenium