This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Numerous studies have suggested relationships between myeloperoxidase, inflammation, and atherosclerosis. MPO-derived reactive chlorinating species (RCS) attack membrane plasmalogens releasing -chloro-fatty aldehydes ( -Cl-FALDs) including 2-chlorohexadecanal (2-ClHDA). The molecular targets of -Cl-FALDs are not known. The current study demonstrates 2-ClHDA adducts with ethanolamine glycerophospholipids and Fmoc-lysine. Utilizing electrospray ionization mass spectrometry, chlorinated adducts were observed that are apparent Schiff base adducts. Reduction of these Schiff base adducts with sodium cyanoborohydride resulted in a novel, stable adduct produced by the elimination of HCl. NMR further confirmed this structure. 2-ClHDA adducts with ethanolamine glycerophospholipids were also substrates for phospholipase D (PLD). The hydrolysis products were derivatized to pentafluorobenzoyl esters, and further structurally confirmed by GCMS. Multiple molecular species of 2-ClHDA-N-modified ethanolamine glycerophospholipids were observed in endothelial cells treated with 2-ClHDA. These results show novel Schiff base adducts of -Cl-FALDs with primary amines, which may represent an important fate of -Cl-FALDs.
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