Tissue-specific regulation of selenoenzyme gene expression during selenium deficiency in rats

G Bermano, F Nicol, J A Dyer, R A Sunde, G J Beckett, J R Arthur, J E Hesketh

Research output: Contribution to journalArticle

245 Citations (Scopus)

Abstract

Regulation of synthesis of the selenoenzymes cytosolic glutathione peroxidase (GSH-Px), phospholipid hydroperoxide glutathione peroxidase (PHGSH-Px) and type-1 iodothyronine 5'-deiodinase (5'IDI) was investigated in liver, thyroid and heart of rats fed on diets containing 0.405, 0.104 (Se-adequate), 0.052, 0.024 or 0.003 mg of Se/kg. Severe Se deficiency (0.003 mg of Se/kg) caused almost total loss of GSH-Px activity and mRNA in liver and heart. 5'IDI activity decreased by 95% in liver and its mRNA by 50%; in the thyroid, activity increased by 15% and mRNA by 95%. PHGSH-Px activity was reduced by 75% in the liver and 60% in the heart but mRNA levels were unchanged; in the thyroid, PHGSH-Px activity was unaffected by Se depletion but its mRNA increased by 52%. Thus there is differential regulation of the three mRNAs and subsequent protein synthesis within and between organs, suggesting both that mechanisms exist to channel Se for synthesis of a particular enzyme and that there is tissue-specific regulation of selenoenzyme mRNAs. During Se depletion, the levels of selenoenzyme mRNA did not necessarily parallel the changes in enzyme activity, suggesting a distinct mechanism for regulating mRNA levels. Nuclear run-off assays with isolated liver nuclei showed severe Se deficiency to have no effect on transcription of the three genes, suggesting that there is post-transcriptional control of the three selenoenzymes, probably involving regulation of mRNA stability.

Original languageEnglish
Pages (from-to)425-430
Number of pages6
JournalBiochemical Journal
Volume311
Issue numberpt 2
Publication statusPublished - 15 Oct 1995

Keywords

  • hydroperoxide glutathione-peroxidase
  • I iodothyronine deiodinase
  • messenger-RNA
  • metabolism
  • CDNA
  • selenocysteine
  • repletion
  • sequence
  • liver

Cite this

Bermano, G., Nicol, F., Dyer, J. A., Sunde, R. A., Beckett, G. J., Arthur, J. R., & Hesketh, J. E. (1995). Tissue-specific regulation of selenoenzyme gene expression during selenium deficiency in rats. Biochemical Journal, 311(pt 2), 425-430.