Abstract 489: Differential Phosphoproteomic Analysis of Platelet Activation by Specific Oxidized Phospholipids and Thrombin Reveals Mechanisms of Platelet Activation in Hyperlipidemia
Jump to

Abstract
We previously showed that specific oxidized phospholipids (oxPCCD36) activate platelets via the scavenger receptor CD36 and promote platelet hyper-reactivity in hyperlipidemia, however the signaling pathway(s) induced in platelets by oxPCCD36 are not defined. We employed mass spectrometry-based phosphoproteomics for the unbiased analysis of changes in protein phosphorylation induced by oxPCCD36 and thrombin, a strong platelet agonist, in human platelets. oxPCCD36 induced changes in phosphorylation of 148 unique phosphorylation sites (116 proteins) while thrombin induced changes of 297 unique sites (181 proteins). Most of the changes in phosphorylation induced by oxPCCD36 and thrombin identified in our study have never been reported before in platelets and include high- and low-abundant proteins with diverse molecular functions located in the plasma membrane, cytosol, or cytoskeleton. Analysis using multiple bioinformatic tools identified protein interaction networks, signaling pathways, activated kinases, and enriched phosphorylation motifs. Comparison between platelet agonists revealed multiple differences including the specific activation of a signaling pathway involving Src-family kinases (SFK), SYK kinase, and PLCγ2 by oxPCCD36. Subsequent biochemical studies in human platelets demonstrated that this pathway is critical for platelet activation by oxPCCD36 and is downstream of CD36. In conclusion, systematic analysis of platelet activation pathways provided novel insights into the mechanism of platelet activation and specific signaling pathways induced by oxidized phospholipids that modulate platelet function in vivo in hyperlipidemia.
- © 2013 by American Heart Association, Inc.
Current Issue
Jump to
Article Tools
- Abstract 489: Differential Phosphoproteomic Analysis of Platelet Activation by Specific Oxidized Phospholipids and Thrombin Reveals Mechanisms of Platelet Activation in HyperlipidemiaAlejandro Zimman, Bjoern Titz, Evangelia Komisopoulou, Thomas G Graeber and Eugene A PodrezArteriosclerosis, Thrombosis, and Vascular Biology. 2013;33:A489, originally published October 20, 2015
Citation Manager Formats
Share this Article
- Abstract 489: Differential Phosphoproteomic Analysis of Platelet Activation by Specific Oxidized Phospholipids and Thrombin Reveals Mechanisms of Platelet Activation in HyperlipidemiaAlejandro Zimman, Bjoern Titz, Evangelia Komisopoulou, Thomas G Graeber and Eugene A PodrezArteriosclerosis, Thrombosis, and Vascular Biology. 2013;33:A489, originally published October 20, 2015