Detection and biological activities of carboxyethylpyrrole ethanolamine phospholipids (CEP-EPs).

Abstract

Oxidation of docosahexaenoate phospholipids produces 4-hydroxy-7-oxo-hept-5-eonyl phospholipids (HOHA-PLs) that react with protein lysyl ε-amino residues to generate 2-ω-carboxyethylpyrrole (CEP) derivatives, endogenous factors that induce angiogenesis in the retina and tumors. It seemed likely, but remained unproven, that HOHA-PLs react with ethanolamine phospholipids (EPs) in vivo to generate CEP-EPs. We now show that CEP-EPs are present in human blood at 4.6-fold higher levels in age-related macular degeneration plasma than in normal plasma. We also show that CEP-EPs are pro-angiogenic, inducing tube formation by human umbilical vein endothelial cells by activating Toll-like receptor 2. CEP-EP levels may be a useful biomarker for clinical assessment of AMD risk and CEP-associated tumor progression and a tool for monitoring the efficacy of therapeutic interventions.

• Authors: Hua Wang, Junhong Guo, Xiaoxia Z West, Hemant K Bid, Liang Lu, Li Hong, Geeng-Fu Jang, Lei Zhang, John W Crabb, Clinical Genomic and Proteomic AMD Study Group, Mikhail Linetsky, Robert G Salomon
• Journal: Chemical research in toxicology (Chem Res Toxicol) Vol. 27 Issue 12 Pg. 2015-22 (Dec 15 2014) ISSN: 1520-5010 [Electronic] United States
• PMID: 25380349 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphatidylethanolamines
• Phospholipids
• phosphatidylethanolamine

Topics

• Chromatography, Liquid
• Human Umbilical Vein Endothelial Cells
• Humans
• Macular Degeneration (blood)
• Magnetic Resonance Spectroscopy
• Phosphatidylethanolamines (blood)
• Phospholipids (blood, physiology)
• Tandem Mass Spectrometry