Protein targets of oxidized phospholipids in endothelial cellss⃞

Journal of Lipid Research

Thomas M. Vondriska¹  Lukasz Koroniak²  Avetis Hekimian³  Andrew D. Watson³  Victoria Duong³  Tabitha Herzog³  B. Gabriel Gugiu⁴  Kevin Mouillesseaux⁴ 

[1] Department of Anesthesiology/Medicine, University of California, Los Angeles, Los Angeles, CA 90095;Department of Chemistry/Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095;Department of Medicine/Cardiology, University of California, Los Angeles, Los Angeles, CA 90095;Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095;

关键词: atherosclerosis;    inflammation;    lipid peroxidation;    mass spectrometry;    lipoproteins;    interleukin-8;   

DOI  :  

来源: DOAJ

【 摘 要 】

Oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (Ox-PAPC) are found in atherosclerotic lesions, apoptotic cells, and oxidized LDL and stimulate human aortic endothelial cells (HAECs) to produce inflammatory cytokines, leukocyte chemoattractants, and coagulation factors. This regulation is thought to be a receptor-mediated process in which oxidized phospholipids activate specific receptors on HAECs to evoke an inflammatory response. To characterize the HAEC proteins with which oxidized phospholipids interact, a biotinylated PAPC analog, 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidyl-(N-biotinylethanolamine) (PAPE-N-biotin), was synthesized. Oxidation of PAPE-N-biotin in air generated a mixture of biotin-labeled oxidized lipids analogous to Ox-PAPC. Ox-PAPE-N-biotin, like Ox-PAPC, induced interleukin-8 (IL-8) protein synthesis and stimulated IL-8, low density lipoprotein receptor, heme oxygenase-1, and activating transcription factor-3 mRNA expression in HAECs. After treatment of HAECs with Ox-PAPE-N-biotin, the cellular proteins were isolated and separated by SDS-PAGE. Western analysis with streptavidin-HRP demonstrated at least 20 different biotinylated HAEC proteins to which the Ox-PAPE-N-biotin was associated, which were not detected with unoxidized PAPE-N-biotin treatment. This work suggests that oxidized phospholipids, such as those found in oxidized LDL, apoptotic cells, and atherosclerotic lesions, form tight interactions with specific endothelial cell proteins, which may be responsible for the inflammatory response. Identification of these putative oxidized phospholipid targets may reveal therapeutic targets to modulate inflammation and atherosclerosis.

【 授权许可】

Unknown