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

This work was supported, in whole or in part, by National Institutes of Health Grants HL067195, HL070819, HL048743, HL107192, and HL108630 (to J. L.); HL46457 and HL48743 (to T. M.); and GM061603 (to V. N. G.). This work was also supported by an American Heart Association postdoctoral fellowship grant (to H. K.) and by Portuguese Fundacao para a Ciencia e a Tecnologia Grants PTDC/SAU-ORG/112683/2009 (to R. C.) and SFRH/BD/73021/2010 (M. B.). ; 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. ; publishersversion ; published