A functional link between housekeeping selenoproteins and phase II enzymes

Aniruddha Sengupta, Bradley A. Carlson, James A. Weaver, Sergey V. Novoselov, Dmitri E. Fomenko, Vadim N. Gladyshev, Dolph L. Hatfield

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Sec (selenocysteine) is biosynthesized on its tRNA and incorporated into selenium-containing proteins (selenoproteins) as the 21st amino acid residue. Selenoprotein synthesis is dependent on Sec tRNA and the expression of this class of proteins can be modulated by altering Sec tRNA expression. The gene encoding Sec tRNA (Trsp) is a single-copy gene and its targeted removal in liver demonstrated that selenoproteins are essential for proper function wherein their absence leads to necrosis and hepatocellular degeneration. In the present study, we found that the complete loss of selenoproteins in liver was compensated for by an enhanced expression of several phase II response genes and their corresponding gene products. The replacement of selenoprotein synthesis in mice carrying mutant Trsp transgenes, wherein housekeeping, but not stress-related selenoproteins are expressed, led to normal expression of phase II response genes. Thus the present study provides evidence for a functional link between housekeeping selenoproteins and phase II enzymes.

Original languageEnglish (US)
Pages (from-to)151-161
Number of pages11
JournalBiochemical Journal
Volume413
Issue number1
DOIs
StatePublished - Jul 1 2008

Keywords

  • Gene expression
  • Liver
  • Microarray
  • Selenocysteine (Sec) tRNA
  • Trsp knockout
  • Xenobiotic

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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