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Type: Journal article
Title: Oxidized LDL-mediated macrophage survival involves elongation factor-2 kinase
Author: Chen, J.
Riazy, M.
Smith, E.
Proud, C.
Steinbrecher, U.
Duronio, V.
Citation: Arteriosclerosis Thrombosis and Vascular Biology, 2009; 29(1):92-98
Publisher: Lippincott Williams & Wilkins
Issue Date: 2009
ISSN: 1079-5642
Statement of
Johnny H. Chen, Maziar Riazy, Ewan M. Smith, Christopher G. Proud, Urs P. Steinbrecher, Vincent Duronio
Abstract: OBJECTIVE— Macrophage survival and proliferation is believed to be a contributing factor in the development of early atherosclerotic lesions. Oxidized low density lipoprotein (oxLDL), a key mediator in the pathogenesis of this disease, has been shown to block apoptosis in macrophages deprived of growth factor. In this report, we investigate the mechanism of oxLDL-mediated macrophage survival. METHODS AND RESULTS— OxLDL, but not native LDL (nLDL), induces an immediate and oscillatory increase in intracellular calcium ([Ca2+]i). We also show that the calcium/calmodulin dependent kinase, eukaryotic elongation factor-2 kinase (eEF2 kinase), is activated in response to oxLDL, an effect that can be blocked by inhibiting calcium mobilization. Furthermore, selective inhibition of eEF2 kinase reverses the prosurvival effect of oxLDL and results in cellular apoptosis. p38 MAP kinase, a negative regulator of eEF2 kinase, is activated on growth factor withdrawal, a response that can be inhibited by oxLDL. Finally, we show that oxLDL, by activating eEF2 kinase, phosphorylates and therefore inhibits eEF2, resulting in an overall decrease in protein synthesis. CONCLUSION— These results indicate a novel signaling pathway in which oxLDL can block macrophage apoptosis by mobilizing calcium and activating eEF2 kinase.
Keywords: Oxidized LDL; eEF2 kinase; macrophage; apoptosis; calcium
Rights: © 2008 American Heart Association, Inc. All rights reserved.
RMID: 0020128183
DOI: 10.1161/ATVBAHA.108.174599
Appears in Collections:Molecular and Biomedical Science publications

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