TY - JOUR
T1 - Myeloperoxidase-derived 2-chlorohexadecanal forms Schiff bases with primary amines of ethanolamine glycerophospholipids and lysine
AU - Wildsmith, Kristin R.
AU - Albert, Carolyn J.
AU - Hsu, Fong Fu
AU - Kao, Jeff L.F.
AU - Ford, David A.
N1 - Funding Information:
This research was supported jointly by NIH grants HL74214 (DF), RR19232 (DF) and RR00954 (Washington University Mass Spectrometry Resource), AHA Established Investigator Grant 0340042N (DF), and a predoctoral fellowship (KW) from the American Heart Association.
PY - 2006/2
Y1 - 2006/2
N2 - Numerous studies have suggested relationships between myeloperoxidase, inflammation, and atherosclerosis. MPO-derived reactive chlorinating species (RCS) attack membrane plasmalogens releasing α-chloro-fatty aldehydes (α-Cl-FALDs) including 2-chlorohexadecanal (2-ClHDA). The molecular targets of α-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 α-Cl-FALDs with primary amines, which may represent an important fate of α-Cl-FALDs.
AB - Numerous studies have suggested relationships between myeloperoxidase, inflammation, and atherosclerosis. MPO-derived reactive chlorinating species (RCS) attack membrane plasmalogens releasing α-chloro-fatty aldehydes (α-Cl-FALDs) including 2-chlorohexadecanal (2-ClHDA). The molecular targets of α-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 α-Cl-FALDs with primary amines, which may represent an important fate of α-Cl-FALDs.
KW - Electrospray ionization mass spectrometry
KW - Endothelial cells
KW - Fatty aldehyde
KW - Phosphatidylethanolamine
KW - Plasmenylcholine
KW - Reactive chlorinating species
UR - http://www.scopus.com/inward/record.url?scp=31844454656&partnerID=8YFLogxK
U2 - 10.1016/j.chemphyslip.2005.12.003
DO - 10.1016/j.chemphyslip.2005.12.003
M3 - Article
C2 - 16417904
AN - SCOPUS:31844454656
SN - 0009-3084
VL - 139
SP - 157
EP - 170
JO - Chemistry and Physics of Lipids
JF - Chemistry and Physics of Lipids
IS - 2
ER -