Free and peptide-bound DOPA can inhibit initiation of low density lipoprotein oxidation.
Hydroxyl radicals have been shown to convert free tyrosine to 3,4-dihydroxyphenyl-alanine (DOPA) which has reducing properties. During protein or peptide oxidation such reducing species are also formed from tyrosine residues. Free DOPA or peptide-bound DOPA (PB-DOPA) is able to promote radical-generating events, facilitating the damage of biomolecules such as nucleic acids. Radical induced lipid oxidation in low density lipoprotein (LDL) transforms the lipoprotein into an atherogenic particle. As PB-DOPA has been found in atherosclerotic plaques, we tested the ability of free and PB-DOPA to influence LDL oxidation. Free DOPA, in contrast to tyrosine had strong inhibitory action on both, the copper-ion initiated and metal ion independent (AAPH-induced) lipid oxidation. Free DOPA also inhibited LDL oxidation induced by the copper transport protein ceruloplasmin. To test if PB-DOPA was also able to inhibit LDL oxidation, DOPA residues were generated enzymatically in the model peptides insulin and tyr-tyr-tyr, respectively. PB-DOPA formation substantially increased the ability of both molecules to inhibit LDL oxidation by copper or AAPH. We hypothesize that DOPA-peptides and -proteins may have the potential to act as efficacious antioxidants in the atherosclerotic plaque.
Exner
Markus
M
Department of Laboratory Medicine, University of Vienna, Vienna, Austria.
Hermann
Marcela
M
Hofbauer
Roland
R
Kapiotis
Stylianos
S
Gmeiner
Bernhard M K
BM
D000975:Antioxidants / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism*; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D007328:Insulin; D008077:Lipoproteins, LDL; D010455:Peptides; D004295:Dihydroxyphenylalanine; D003300:Copper; D002570:Ceruloplasmin