Pathways of phospholipid oxidation by HOCl in human LDL detected by LC-MS.
A wealth of evidence now indicates that low-density lipoprotein (LDL) must be modified to promote atherosclerosis, and that this may involve oxidants released by phagocytes. Many studies of oxidative damage in atherosclerosis previously have concentrated on damage by nonhalogenated oxidants, but HOCl is a highly toxic oxidant produced by myeloperoxidase in phagocytes, which is also likely to be important in the disease pathogenesis. Currently some controversy exists over the products resulting from reaction of HOCl with LDL lipids, in particular regarding whether predominantly chlorohydrins or lipid peroxides are formed. In this study LC-MS of phosphatidylcholines in human LDL treated either with HOCl or the myeloperoxidase system was used as a specific method to detect chlorohydrin and peroxide formation simultaneously, and with comparable sensitivity. Chlorohydrin products from lipids containing oleic, linoleic and arachidonic acids were detected, but no hydroperoxides of linoleoyl or arachidonoyl lipids could be observed. This study provides the first direct evidence that lipid chlorohydrins rather than peroxides are the major products of HOCl- or myeloperoxidase-treated LDL phospholipids. This in turn provides important information required for the study of oxidative damage in vivo which will allow the type and source of oxidants involved in the pathology of atherosclerosis to be investigated.
Jerlich
A
A
Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, United Kingdom.
Pitt
A R
AR
Schaur
R J
RJ
Spickett
C M
CM
D000328:Adult; D001161:Arteriosclerosis / Q000209:etiology; D002728:Chlorohydrins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000032:analysis / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*
D002728:Chlorohydrins; D005609:Free Radicals; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D010743:Phospholipids; D006997:Hypochlorous Acid; D009195:Peroxidase