Oxidative modification of low-density lipoprotein: lipid peroxidation by myeloperoxidase in the presence of nitrite.
Oxidative modification of low-density lipoprotein (LDL) is a pivotal process in early atherogenesis and can be brought about by myeloperoxidase (MPO), which is capable of reacting with nitrite, a NO metabolite. We studied MPO-mediated formation of conjugated dienes in isolated human LDL in dependence on the concentrations of nitrite and chloride. This reaction was strongly stimulated by low concentrations (5-50 microM) of nitrite which corresponds to the reported concentration in the arterial vessel wall. Under these conditions no protein tyrosine nitration occurred; this reaction required much higher nitrite concentrations (100 microM-1 mM). Chloride neither supported lipid peroxidation alone nor was its presence mandatory for the effect of nitrite. We propose a prominent role of lipid peroxidation for the proatherogenic action of the MPO/nitrite system, whereas peroxynitrite may be competent for protein tyrosine nitration of LDL. Monomeric and oligomeric flavan-3-ols present in cocoa products effectively counteracted, at micromolar concentrations, the MPO/nitrite-mediated lipid peroxidation of LDL. Flavan-3-ols also suppressed protein tyrosine nitration induced by MPO/nitrite or peroxynitrite as well as Cu2+-mediated lipid peroxidation of LDL. This multi-site protection by (-)-epicatechin or other flavan-3-ols against proatherogenic modification of LDL may contribute to the purported beneficial effects of dietary flavan-3-ols for the cardiovascular system.
Kraemer
Tilo
T
Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, P.O. Box 10 10 07, D-40001 Düsseldorf, Germany.
Prakosay
Inthanongsack
I
Date
Rahul A
RA
Sies
Helmut
H
Schewe
Tankred
T
D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009573:Nitrites / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism*
D005419:Flavonoids; D008077:Lipoproteins, LDL; D009573:Nitrites; C404987:flavan-3-ol; D009195:Peroxidase