Activation of Aortic Endothelial Cells by Oxidized Phospholipids: A Phosphoproteomic Analysis

被引:34
|
作者
Zimman, Alejandro [3 ]
Chen, Sharon S. [1 ,2 ]
Komisopoulou, Evangelia [1 ,2 ]
Titz, Bjoern [1 ,2 ]
Martinez-Pinna, Roxana [3 ]
Kafi, Aarya [3 ]
Berliner, Judith A. [3 ,4 ]
Graeber, Thomas G. [1 ,2 ,5 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Crump Inst Mol Imaging, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Med, Los Angeles, CA 90095 USA
关键词
Oxidized phospholipid; Ox-PAPC; endothelial cell; atherosclerosis; phosphoproteomics; signal transduction; phosphatase inhibitor; LOW-DENSITY-LIPOPROTEIN; MASS-SPECTROMETRY; PHOSPHORYLATION ANALYSIS; LIQUID-CHROMATOGRAPHY; DATA SETS; RECEPTOR; IDENTIFICATION; TRANSCRIPTION; ALIGNMENT; BINDING;
D O I
10.1021/pr901194x
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have shown that oxidized products of the phospholipid PAPC (Ox-PAPC) are strong activators of aortic endothelial cells and play an important role in atherosclerosis and other inflammatory diseases. We and others have demonstrated that Ox-PAPC activates specific signaling pathways and regulates a large number of genes. Using a phosphoproteomic approach based on phosphopeptide enrichment and mass spectrometry analysis, we identified candidate changes in Ox-PAPC-induced protein phosphorylation of 228 proteins. Functional annotation of these proteins showed an enrichment of the regulation of cytoskeleton, junctional components, and tyrosine kinases, all of which may contribute to the phenotypic and molecular changes observed in endothelial cells treated with Ox-PAPC. Many changes in protein phosphorylation induced by Ox-PAPC are reported here for the first time and provide new insights into the mechanism of activation by oxidized lipids, including phosphorylation-based signal transduction.
引用
收藏
页码:2812 / 2824
页数:13
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