Distinct HDL subclasses present similar intrinsic susceptibility to oxidation by HOCl.
The heme protein myeloperoxidase (MPO) functions as a catalyst for lipoprotein oxidation. Hypochlorous acid (HOCl), a potent two-electron oxidant formed by the MPO-H(2)O(2)-chloride system of activated phagocytes, modifies antiatherogenic high-density lipoprotein (HDL). The structural heterogeneity and oxidative susceptibility of HDL particle subfractions were probed with HOCl. All distinct five HDL subfraction were modified by HOCl as demonstrated by the consumption of tryptophan residues and free amino groups, cross-linking of apolipoprotein AI, formation of HOCl-modified epitopes, increased electrophoretic mobility and altered content of unsaturated fatty acids in HDL subclasses. Small, dense HDL3 were less susceptible to oxidative modification than large, light HDL2 on a total mass basis at a fixed HOCl:HDL mass ratio of 1:32, but in contrast not on a particle number basis at a fixed HOCl:HDL molar ratio of 97:1. We conclude that structural and physicochemical differences between HDL subclasses do not influence their intrinsic susceptibility to oxidative attack by HOCl.
Chantepie
Sandrine
S
Université Pierre et Marie Curie-Paris 6, UMR S939 "Dyslipydemia, Inflammation and Atherosclerosis in Metabolic Diseases", F-75013 Paris, France. sandrine.chantepie@upmc.fr
Malle
Ernst
E
Sattler
Wolfgang
W
Chapman
M John
MJ
Kontush
Anatol
A
D050197:Atherosclerosis / Q000097:blood / Q000209:etiology; D001797:Blood Protein Electrophoresis; D004587:Electrophoresis, Agar Gel; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry* / Q000145:classification* / Q000187:drug effects; D053439:Lipoproteins, HDL2 / Q000097:blood / Q000737:chemistry / Q000187:drug effects; D053440:Lipoproteins, HDL3 / Q000097:blood / Q000737:chemistry / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D014364:Tryptophan / Q000737:chemistry
D005231:Fatty Acids, Unsaturated; D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D016877:Oxidants; D006997:Hypochlorous Acid; D014364:Tryptophan