Pathways of phospholipid oxidation by HOCL in human LDL detected by LC-MS

A. Jerlich, A.R. Pitt, R.J. Schaur, C.M. Spickett

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)673-682
Number of pages9
JournalFree Radical Biology and Medicine
Volume28
Issue number5
DOIs
Publication statusPublished - 1 Mar 2000

Keywords

  • atherosclerosis
  • chlorohydrins
  • electrospray ionization mass spectrometry
  • HPLC
  • hypochlorous acid
  • lipid peroxidation
  • low density lipoprotein
  • myeloperoxidase
  • free radicals

Fingerprint Dive into the research topics of 'Pathways of phospholipid oxidation by HOCL in human LDL detected by LC-MS'. Together they form a unique fingerprint.

  • Cite this