Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression

Madalena Barroso, Cristina Florindo, Hermann Kalwa, Zélia Silva, Anton A. Turanov, Bradley A. Carlson, Isabel Tavares De Almeida, Henk J. Blom, Vadim N. Gladyshev, Dolph L. Hatfield, Thomas Michel, Rita Castro, Joseph Loscalzo, Diane E. Handy

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Background: Methylation of tRNASec facilitates the incorporation of selenocysteine at a UGA codon during translation. Results: Accumulation of the homocysteine precursor S-adenosylhomocysteine decreases tRNASec methylation, reducing glutathione peroxidase 1 expression and increasing oxidative stress-induced inflammatory activation of endothelial cells. Conclusion: Methylation modulates the expression of selenoproteins to regulate redox-dependent inflammatory pathways. Significance: Hypomethylation stress promotes a proatherogenic endothelial cell phenotype.

Original languageEnglish (US)
Pages (from-to)15350-15362
Number of pages13
JournalJournal of Biological Chemistry
Volume289
Issue number22
DOIs
StatePublished - May 30 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Barroso, M., Florindo, C., Kalwa, H., Silva, Z., Turanov, A. A., Carlson, B. A., De Almeida, I. T., Blom, H. J., Gladyshev, V. N., Hatfield, D. L., Michel, T., Castro, R., Loscalzo, J., & Handy, D. E. (2014). Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression. Journal of Biological Chemistry, 289(22), 15350-15362. https://doi.org/10.1074/jbc.M114.549782