LC-ESI/MS reveals unusual oxygenated lysophosphatidylserines produced after oxidation and hydrolysis by plasma lipoprotein-associated phospholipase A2 of sn-1, sn-2-dilinoleoyl-PS.
Tyurin-VA; Tyurina-YY; Macphee-CH; Kagan-VE
Toxicologist 2011 Mar; 120(Suppl 2):359
Oxidation and hydrolisis of phospholipids (PL), containing oxidizable residues in sn-2 position, play an essential role in the production of signaling molecules - oxygenated fatty acids (FA) and lyso-PL. The presence of oxidizable FA - in both sn-1 and sn-2 positions - may yield - upon oxidation and hydrolysis by phospholipases A2 (PLA2) - a large variety of oxidized species and non-oxidized species with potentially effective regulatory propensities. In particular, oxidative/hydrolytic metabolism of doubly polyunsaturated phosphatitdylserines (PS) may play a central role in the molecular mechanisms of apoptosis and clearance of apoptotic cells. We present the results on structural characterization of oxygenated molecular species of PS containing linoleic acid in sn-2 position (C18:0/C18:2) and in both sn-1 and sn-2 position (C18:2/C18:2) formed in cytochrome c/H2O2 driven reaction. Oxidation of PS(C18:2/C18:2) resulted in formation of products at m/z 798, 814, 830 and 846, which included OH, OOH, OH/OOH and 2OOH groups, respectively. We characterized PS hydrolysis products (lyso-PS and free FA, FFA) formed by lipoprotein-associated PLA2 - secreted type VIIA PLA2 and cytosolic type VIIB PLA2. PS was preferable substrate for VIIA PLA2. Accumulation of hydrolysis products was markedly greater after hydrolysis of oxidized PS than non-oxidized PS. The products were mainly oxygenated FFA and non-oxidized lyso-PS. Hydrolysis of oxidized PS (C18:2/C18:2), led to generation of a great variety of both oxygenated and non-oxygenated lyso-PS and FFA. We suggest that both oxidatively modified FFA and lyso-PS may represent important signals facilitating and regulating execution of apoptotic and phagocytotic programs essential for control of inflammation.
Biological-effects; Cell-biology; Cell-function; Cell-metabolism; Cell-morphology; Cellular-reactions; Chemotherapy; Cytology; Microscopic-analysis; Microscopy; Molecular-biology; Molecular-structure; Oxidative-metabolism; Oxidative-phosphorylation; Oxidative-processes; Physiological-effects; Quantitative-analysis
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
University of Pittsburgh at Pittsburgh