Please use this identifier to cite or link to this item: http://hdl.handle.net/10362/40318
Title: Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression
Author: Barroso, Madalena
Florindo, Cristina
Kalwa, Hermann
Silva, Zélia
Turanov, Anton A.
Carlson, Bradley A.
De Almeida, Isabel Tavares
Blom, Henk J.
Gladyshev, Vadim N.
Hatfield, Dolph L.
Michel, Thomas
Castro, Rita
Loscalzo, Joseph
Handy, Diane E.
Keywords: Biochemistry
Molecular Biology
Cell Biology
Issue Date: 30-May-2014
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.
Description: 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.).
Peer review: yes
URI: http://www.scopus.com/inward/record.url?scp=84901724596&partnerID=8YFLogxK
DOI: https://doi.org/10.1074/jbc.M114.549782
ISSN: 0021-9258
Appears in Collections:NMS: CEDOC - Artigos em revista internacional com arbitragem científica

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