Peroxynitrite mediated linoleic acid oxidation and tyrosine nitration in the presence of synthetic neuromelanins.
Peroxynitrite-mediated linoleic acid oxidation and tyrosine nitration were analysed in the presence of synthetic model neuromelanins: dopamine (DA) -melanin, cysteinyldopamine (CysDA) -melanin and various DA/CysDA copolymers. The presence of melanin significantly decreased the amount of 3-nitrotyrosine formed. This inhibitory effect depended on the type and concentration of melanin polymer. It was found that incorporation of CysDA-derived units into melanin attenuated its protective effect on tyrosine nitration induced by peroxynitrite. In the presence of bicarbonate, the melanins also inhibited 3-nitrotyrosine formation in a concentration dependent manner, although the extent of inhibition was lower than in the absence of bicarbonate. The tested melanins inhibited peroxynitrite-induced formation of linoleic acid hydroperoxides, both in the absence and in the presence of bicarbonate. In the presence of bicarbonate, among the oxidation products appeared 4-hydroxynonenal (HNE). CysDA-melanin inhibited the formation of HNE, while DA-melanin did not affect the aldehyde level. The results of the presented study suggest that neuromelanin can act as a natural scavenger of peroxynitrite.
Stepień
K
K
Department of Molecular Biology, Biochemistry and Biopharmacy, Faculty of Pharmacy, Medical University of Silesia, Sosnowiec, Poland. kstepien@farmant.slam.katowice.pl
Wilczok
A
A
Zajdel
A
A
Dzierzega-Lecznar
A
A
Wilczok
T
T
D000447:Aldehydes / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019787:Linoleic Acid / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D000447:Aldehydes; D003432:Cross-Linking Reagents; D008543:Melanins; C014121:neuromelanin; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D019787:Linoleic Acid; D006861:Hydrogen Peroxide; C027576:4-hydroxy-2-nonenal; D009584:Nitrogen; D010100:Oxygen