Fatty acid and phospholipid chlorohydrins cause cell stress and endothelial adhesion

Gary Dever, Cherry L. Wainwright, Simon Kennedy, Corinne M. Spickett

Research output: Contribution to journalArticle

Abstract

The oxidation of low-density lipoprotein (LDL) is thought to contribute to atherogenesis, which is an inflammatory disease involving activation of phagocytic cells. Myeloperoxidase, an enzyme which is able to produce hypochlorous acid (HOCl), is released from these phagocytic cells, and has been found in an active form in atherosclerotic plaques. HOCl can oxidize both the lipid and protein moiety of LDL, and HOCl-modified LDL has been found to be pro-inflammatory, although it is not known which component is responsible for this effect. As HOCl can oxidize lipids to give chlorohydrins, we hypothesized that phospholipid chlorohydrins might have toxic and pro-inflammatory effects. We have formed chlorohydrins from fatty acids (oleic, linoleic and arachidonic acids) and from phospholipids (stearoyl-oleoyl phosphatidylcholine, stearoyl-linoleoyl phosphatidylcholine and stearoyl-arachidonoyl phosphatidylcholine), and investigated various biological effects of these oxidation products. Fatty acid and phospholipid chlorohydrins were found to deplete ATP levels in U937 cells in a concentration-dependent manner, with significant effects observed at concentrations of 25 µM and above. Low concentrations (25 µM) of stearoyl-oleoyl phosphatidylcholine and stearoyl-arachidonoyl phosphatidylcholine chlorohydrins were also found to increase caspase-3 activity. Finally, stearoyl-oleoyl phosphatidylcholine chlorohydrin increased leukocyte adhesion to artery segments isolated from C57Bl/6 mice. These results demonstrate potentially harmful effects of lipid chlorohydrins, and suggest that they may contribute to some of the pro-inflammatory effects that HOCl-modified low density lipoprotein has been found to induce.
Original languageEnglish
Pages (from-to)761-768
Number of pages8
JournalActa Biochimica Polonica
Volume53
Issue number4
Publication statusPublished - 2006

Keywords

  • chlorinated phospholipids
  • chlorinated fatty acids
  • ATP depletion
  • atherosclerosis
  • leukocyte adhesion
  • low-density-lipoprotein
  • human atherosclerotic lesions
  • hypochlorous acid
  • oxidized phospholipids
  • mass-spectrometry
  • oxidative stress
  • myeloperoxidase
  • atherogenesis
  • apoptosis
  • identification
  • Biology

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