Tyrosine nitration catalyzed by copper (II)

Abstract

Tyrosine nitration is often observed during neurodegenerative disorders under nitrative stress. This protein posttranslational modification can be induced by peroxynitrite or nitrogen dioxide (NO2). In this study, the role of cupric ions on catalyzing tyrosine nitration was investigated by development of a microfluidic chip working as a microreactor [1] . The microfluidic chip acted also as an emitter for electrospray ionization mass spectrometry to online detect the nitration products. We found that cupric ions can efficiently catalyze tyrosine nitration in the presence of nitric oxide (NO), oxygen and H2O2, or in the presence of nitrite and H2O2. With mechanism study, we showed that cupric ions and peptide-cupric ion complexes are excellent Fenton-catalysts, even better than Fe (III) or heme, for the formation of hydroxyl radicals (OH) and/or copper (II)-bound OH from hydrogen peroxide. These radicals were efficiently scavenged by tyrosine to form tyrosine radicals and by nitrite to form NO2, leading to tyrosine nitration in polypeptides. This study shows that copper has a polyvalent role in the processes of tyrosine nitration.