Peroxynitrite and heme protein--mediated nitrative/oxidative modification of human plasma protein: the role of free radical scavenging vs. complex forming.
The major pathways of protein tyrosine nitration in vivo include peroxynitrite (ONOO(-)) and heme peroxidase-NO(2)(-)-H(2)O(2) dependent reaction in which free radicals and iron catalysis are involved. In this paper, we chose three classic antioxidants (GSH, a major intracellular antioxidant; Trolox, a phenolic antioxidant without chelating effect; and DFO, a good iron chelator), to study their efficiencies against ONOO(-) or heme/NaNO(2)/H(2)O(2) - mediated nitrative/oxidative damage to human plasma proteins in vitro. Protein nitration was efficiently inhibited by the three antioxidants regardless of nitration pathways, whereas the efficiencies of antioxidants on protein oxidation depended on the concentration of antioxidants and categories of oxidant. In both models, GSH exhibited protective activity in protein oxidation and Trolox promoted the formation of plasma protein carbonyl groups at lower concentration (0.01 and 0.1mM). DFO dose-dependently inhibited ONOO(-)-induced protein oxidation, while it enhanced heme/NaNO(2)/H(2)O(2)-triggered protein oxidation at lower concentration. However, both DFO and Trolox exhibited protective effect on protein carbonyl formation when the higher concentration was used. The pro-oxidant or antioxidant effect for these antioxidants at different concentration, may provide useful information about the selection of the suitable antioxidant and dosage in experimental and clinical application.
Lu
Naihao
N
Department of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, PR China.
Zhou
Guofeng
G
Pei
Di
D
Yi
Lian
L
Gao
Zhonghong
Z
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism*; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology; D003676:Deferoxamine / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology; D006420:Hemeproteins / Q000378:metabolism*; D006801:Humans; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D001798:Blood Proteins; D002839:Chromans; D016166:Free Radical Scavengers; D006420:Hemeproteins; D016877:Oxidants; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D005978:Glutathione; D003676:Deferoxamine; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid