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Epoxyisoprostane andEpoxycyclopentenonePhospholipidsRegulate MonocyteChemotactic Protein-1and Interleukin-8Synthesis Ganesamoorthy SubbanagounderJason W.H. WongHans C. Lee2002 год

Epoxyisoprostane and Epoxycyclopentenone Phospholipids Regulate Monocyte Chemotactic Protein-1 and Interleukin-8 Synthesis
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Аннотация: Monocyte recruitment to the vessel wall, mediated by monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8), plays an important role in atherogenesis. We have shown previously that minimally oxidized low density lipoprotein, oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (Ox-PAPC), activates endothelial cells to produce MCP-1 and IL-8. By using liquid chromatography/mass spectrometry methods coupled with bioassay, we report a family of epoxyisoprostane (PEIPC) and epoxycyclopentenone (PECPC) phospholipids that are the components of Ox-PAPC responsible for the majority of this activity. Ox-PAPC contains five chromatographically distinguishable active PEIPC components (m/z 825.5) and four PECPC components (m/z 810.5). All nine components induced endothelial cell synthesis of IL-8 and MCP-1 in a dose-dependent fashion between 0.1 and 5 microm concentrations. The five PEIPC components had identical functional groups and all underwent dehydration to produce m/z 810.5. We present evidence that these phospholipids are regioisomers with epoxide groups at the 5,6-, 8,9-, 11,12-, or 14,15-positions of the sn-2 fatty acid and their epoxide groups is important for biological activity. We have shown previously that peroxisome proliferator-activated receptor alpha is involved in MCP-1 synthesis in response to Ox-PAPC. We now show that PEIPC and PECPC isomers are potent activators of peroxisome proliferator-activated receptor alpha. PEIPC and PECPC isomers are strongly recognized by specific circulating murine natural autoantibodies (EO6) and accumulate in cells treated with IL-1beta. These studies demonstrate that PEIPC and PECPC isomers are potent activators of endothelial cells increasing synthesis of IL-8 and MCP-1. Their accumulation in cells exposed to cytokines and in atherosclerotic lesions suggests that these lipids may play a role in a number of chronic disease processes.
Год издания: 2002
Авторы: Ganesamoorthy Subbanagounder, Jason W.H. Wong, Hans C. Lee, Kym F. Faull, Elizabeth R. Miller, Joseph L. Witztum, Judith A. Berliner
Издательство: Elsevier BV
Источник: Journal of Biological Chemistry
Ключевые слова: Eicosanoids and Hypertension Pharmacology, Chemokine receptors and signaling, Antioxidant Activity and Oxidative Stress
Другие ссылки: Journal of Biological Chemistry (PDF)
Journal of Biological Chemistry (HTML)
PubMed (HTML)