Abstract
Human cytomegalovirus (HCMV) exerts anti-apoptotic effect during early stage of infection, which provides HCMV time for propagation. We investigated pathways mediating the resistance to H(2)O(2)-induced cell death - a self-defense mechanism to remove infected cells. We found that human aortic endothelial cells (HAECs) infected with VHL/E strain of HCMV during first 3 days were resistant to H(2)O(2) (0-2 mM) induced apoptosis. This anti-apoptotic effect may be mediated by the upregulation of Bcl-2, an anti-apoptotic protein through the activation pro-survival pathway extracellular signal regulated kinase (ERK). Through this mechanism, HCMV is able to propagate and causes endothelial dysfunction, hence vascular disease.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Apoptosis / drug effects*
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Caspase 3
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Caspases / metabolism
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Cells, Cultured
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Cytomegalovirus / physiology*
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Endothelial Cells / cytology
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Endothelial Cells / drug effects*
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Endothelial Cells / enzymology
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Endothelial Cells / virology*
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Enzyme Activation / drug effects
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Humans
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Hydrogen Peroxide / pharmacology*
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Intracellular Membranes / drug effects
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MAP Kinase Signaling System / drug effects*
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Membrane Potentials / drug effects
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phosphorylation
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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RNA, Messenger / genetics
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Up-Regulation
Substances
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Hydrogen Peroxide
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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CASP3 protein, human
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Caspase 3
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Caspases