Identification of novel bioactive aldehyde-modified phosphatidylethanolamines formed by lipid peroxidation.
Lipid aldehydes generated by lipid peroxidation induce cell damage and inflammation. Recent evidence indicates that γ-ketoaldehydes (isolevuglandins, IsoLGs) form inflammatory mediators by modifying the ethanolamine headgroup of phosphatidylethanolamines (PEs). To determine if other species of aldehyde-modified PEs (al-PEs) with inflammatory bioactivity were generated by lipid peroxidation, we oxidized liposomes containing arachidonic acid and characterized the resulting products. We detected PE modified by IsoLGs, malondialdehyde (MDA), and 4-hydroxynonenal (HNE), as well as a novel series of N-acyl-PEs and N-carboxyacyl-PEs in these oxidized liposomes. These al-PEs were also detected in high-density lipoproteins exposed to myeloperoxidase. When we tested the ability of al-PEs to induce THP-1 monocyte adhesion to cultured endothelial cells, we found that PEs modified by MDA, HNE, and 4-oxononenal induced adhesion with potencies similar to those of PEs modified by IsoLGs (∼2μM). A commercially available medium-chain N-carboxyacyl-PE (C11:0CAPE) also stimulated adhesion, whereas C4:0CAPE and N-acyl-PEs did not. PEs modified by acrolein or by glucose were only partial agonists for adhesion. These studies indicate that lipid peroxidation generates a large family of al-PEs, many of which have the potential to drive inflammation.
Division of Clinical Pharmacology Vanderbilt University at Nashville, Nashville, TN 37232, USA.
Lilu
L
Guo
Zhongyi
Z
Chen
Venkataraman
V
Amarnath
Sean S
SS
Davies
D000447:Aldehydes / Q000737:chemistry*; D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000737:chemistry; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D008315:Malondialdehyde / Q000737:chemistry*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011453:Prostaglandins / Q000737:chemistry* / Q000378:metabolism; D053719:Tandem Mass Spectrometry
D000447:Aldehydes; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011453:Prostaglandins; D016718:Arachidonic Acid; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal