title: Myeloperoxidase-derived 2-chlorohexadecanal forms Schiff bases with primary amines of ethanolamine glycerophospholipids and lysine.
abstract: Numerous studies have suggested relationships between myeloperoxidase, inflammation, and atherosclerosis. MPO-derived reactive chlorinating species (RCS) attack membrane plasmalogens releasing alpha-chloro-fatty aldehydes (alpha-Cl-FALDs) including 2-chlorohexadecanal (2-ClHDA). The molecular targets of alpha-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 GC-MS. 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 alpha-Cl-FALDs with primary amines, which may represent an important fate of alpha-Cl-FALDs.
authors.affiliation: Department of Biochemistry and Molecular Biology, St. Louis University Health Sciences Center, St. Louis, MO 63104, United States.
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Wildsmith
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Albert
authors.forename: Fong-Fu
authors.initials: FF
authors.lastname: Hsu
authors.forename: Jeff L-F
authors.initials: JL
authors.lastname: Kao
authors.forename: David A
authors.initials: DA
authors.lastname: Ford
mesh_terms: D000447:Aldehydes / Q000737:chemistry* / Q000494:pharmacology; D000588:Amines / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003331:Coronary Vessels / Q000737:chemistry; D042783:Endothelial Cells / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D008239:Lysine / Q000737:chemistry*; D015394:Molecular Structure; D009195:Peroxidase / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000037:antagonists & inhibitors / Q000737:chemistry*; D012545:Schiff Bases / Q000138:chemical synthesis / Q000737:chemistry; D013997:Time Factors
chemical_list: C432398:2-chlorohexadecanal; D000447:Aldehydes; D000588:Amines; D010714:Phosphatidylethanolamines; D012545:Schiff Bases; D009195:Peroxidase; D008239:Lysine