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

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

in: J BIOL CHEM, Jahrgang 289, Nr. 22, 30.05.2014, S. 15350-62.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Barroso, M, Florindo, C, Kalwa, H, Silva, Z, Turanov, AA, Carlson, BA, de Almeida, IT, Blom, HJ, Gladyshev, VN, Hatfield, DL, Michel, T, Castro, R, Loscalzo, J & Handy, DE 2014, 'Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression', J BIOL CHEM, Jg. 289, Nr. 22, S. 15350-62. https://doi.org/10.1074/jbc.M114.549782

APA

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. J BIOL CHEM, 289(22), 15350-62. https://doi.org/10.1074/jbc.M114.549782

Vancouver

Barroso M, Florindo C, Kalwa H, Silva Z, Turanov AA, Carlson BA et al. Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression. J BIOL CHEM. 2014 Mai 30;289(22):15350-62. https://doi.org/10.1074/jbc.M114.549782

Bibtex

@article{b1e1740a85a14ff4b50d6cbd52963e8a,
title = "Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression",
abstract = "S-adenosylhomocysteine (SAH) is a negative regulator of most methyltransferases and the precursor for the cardiovascular risk factor homocysteine. We have previously identified a link between the homocysteine-induced suppression of the selenoprotein glutathione peroxidase 1 (GPx-1) and endothelial dysfunction. Here we demonstrate a specific mechanism by which hypomethylation, promoted by the accumulation of the homocysteine precursor SAH, suppresses GPx-1 expression and leads to inflammatory activation of endothelial cells. The expression of GPx-1 and a subset of other selenoproteins is dependent on the methylation of the tRNA(Sec) to the Um34 form. The formation of methylated tRNA(Sec) facilitates translational incorporation of selenocysteine at a UGA codon. Our findings demonstrate that SAH accumulation in endothelial cells suppresses the expression of GPx-1 to promote oxidative stress. Hypomethylation stress, caused by SAH accumulation, inhibits the formation of the methylated isoform of the tRNA(Sec) and reduces GPx-1 expression. In contrast, under these conditions, the expression and activity of thioredoxin reductase 1, another selenoprotein, is increased. Furthermore, SAH-induced oxidative stress creates a proinflammatory activation of endothelial cells characterized by up-regulation of adhesion molecules and an augmented capacity to bind leukocytes. Taken together, these data suggest that SAH accumulation in endothelial cells can induce tRNA(Sec) hypomethylation, which alters the expression of selenoproteins such as GPx-1 to contribute to a proatherogenic endothelial phenotype.",
keywords = "Cell Adhesion, Endothelial Cells, Glutathione Peroxidase, Homocysteine, Human Umbilical Vein Endothelial Cells, Humans, Hydrogen Peroxide, Leukocytes, Methylation, Methyltransferases, Oxidative Stress, RNA, Transfer, Amino Acyl, RNA, Transfer, Ser, S-Adenosylhomocysteine, S-Adenosylmethionine, Selenium, Selenoproteins, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Madalena Barroso and Cristina Florindo and Hermann Kalwa and Z{\'e}lia Silva and Turanov, {Anton A} and Carlson, {Bradley A} and {de Almeida}, {Isabel Tavares} and Blom, {Henk J} and Gladyshev, {Vadim N} and Hatfield, {Dolph L} and Thomas Michel and Rita Castro and Joseph Loscalzo and Handy, {Diane E}",
note = "{\textcopyright} 2014 by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2014",
month = may,
day = "30",
doi = "10.1074/jbc.M114.549782",
language = "English",
volume = "289",
pages = "15350--62",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "22",

}

RIS

TY - JOUR

T1 - Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression

AU - Barroso, Madalena

AU - Florindo, Cristina

AU - Kalwa, Hermann

AU - Silva, Zélia

AU - Turanov, Anton A

AU - Carlson, Bradley A

AU - de Almeida, Isabel Tavares

AU - Blom, Henk J

AU - Gladyshev, Vadim N

AU - Hatfield, Dolph L

AU - Michel, Thomas

AU - Castro, Rita

AU - Loscalzo, Joseph

AU - Handy, Diane E

N1 - © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2014/5/30

Y1 - 2014/5/30

N2 - S-adenosylhomocysteine (SAH) is a negative regulator of most methyltransferases and the precursor for the cardiovascular risk factor homocysteine. We have previously identified a link between the homocysteine-induced suppression of the selenoprotein glutathione peroxidase 1 (GPx-1) and endothelial dysfunction. Here we demonstrate a specific mechanism by which hypomethylation, promoted by the accumulation of the homocysteine precursor SAH, suppresses GPx-1 expression and leads to inflammatory activation of endothelial cells. The expression of GPx-1 and a subset of other selenoproteins is dependent on the methylation of the tRNA(Sec) to the Um34 form. The formation of methylated tRNA(Sec) facilitates translational incorporation of selenocysteine at a UGA codon. Our findings demonstrate that SAH accumulation in endothelial cells suppresses the expression of GPx-1 to promote oxidative stress. Hypomethylation stress, caused by SAH accumulation, inhibits the formation of the methylated isoform of the tRNA(Sec) and reduces GPx-1 expression. In contrast, under these conditions, the expression and activity of thioredoxin reductase 1, another selenoprotein, is increased. Furthermore, SAH-induced oxidative stress creates a proinflammatory activation of endothelial cells characterized by up-regulation of adhesion molecules and an augmented capacity to bind leukocytes. Taken together, these data suggest that SAH accumulation in endothelial cells can induce tRNA(Sec) hypomethylation, which alters the expression of selenoproteins such as GPx-1 to contribute to a proatherogenic endothelial phenotype.

AB - S-adenosylhomocysteine (SAH) is a negative regulator of most methyltransferases and the precursor for the cardiovascular risk factor homocysteine. We have previously identified a link between the homocysteine-induced suppression of the selenoprotein glutathione peroxidase 1 (GPx-1) and endothelial dysfunction. Here we demonstrate a specific mechanism by which hypomethylation, promoted by the accumulation of the homocysteine precursor SAH, suppresses GPx-1 expression and leads to inflammatory activation of endothelial cells. The expression of GPx-1 and a subset of other selenoproteins is dependent on the methylation of the tRNA(Sec) to the Um34 form. The formation of methylated tRNA(Sec) facilitates translational incorporation of selenocysteine at a UGA codon. Our findings demonstrate that SAH accumulation in endothelial cells suppresses the expression of GPx-1 to promote oxidative stress. Hypomethylation stress, caused by SAH accumulation, inhibits the formation of the methylated isoform of the tRNA(Sec) and reduces GPx-1 expression. In contrast, under these conditions, the expression and activity of thioredoxin reductase 1, another selenoprotein, is increased. Furthermore, SAH-induced oxidative stress creates a proinflammatory activation of endothelial cells characterized by up-regulation of adhesion molecules and an augmented capacity to bind leukocytes. Taken together, these data suggest that SAH accumulation in endothelial cells can induce tRNA(Sec) hypomethylation, which alters the expression of selenoproteins such as GPx-1 to contribute to a proatherogenic endothelial phenotype.

KW - Cell Adhesion

KW - Endothelial Cells

KW - Glutathione Peroxidase

KW - Homocysteine

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Hydrogen Peroxide

KW - Leukocytes

KW - Methylation

KW - Methyltransferases

KW - Oxidative Stress

KW - RNA, Transfer, Amino Acyl

KW - RNA, Transfer, Ser

KW - S-Adenosylhomocysteine

KW - S-Adenosylmethionine

KW - Selenium

KW - Selenoproteins

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1074/jbc.M114.549782

DO - 10.1074/jbc.M114.549782

M3 - SCORING: Journal article

C2 - 24719327

VL - 289

SP - 15350

EP - 15362

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 22

ER -