Dopamine-melanin protects against tyrosine nitration, tryptophan oxidationand Ca2+-ATPase inactivation induced by peroxynitrite

The effects of dopamine-melanin (DA-melanin), a synthetic model of neuromel anin, on peroxynitrite-mediated 3-nitrotyrosine formation, oxidation of try ptophan in bovine serum albumin and inactivation of erythrocyte membrane Ca 2+-ATPase activity were investigated in the absence and in the presence of bicarbonate. DA-melanin inhibited nitration of free tyrosine, loss of trypt ophan residues and Ca2+-ATPase inactivation by peroxynitrite in a dose depe ndent manner. In the presence of bicarbonate, this inhibitory effect was lo wer for nitration and insignificant for oxidative protein modifications. Th ese results suggest that neuromelanin can protect against nitrating and oxi dizing action of peroxynitrite but is a worse protector against the peroxyn itrite-CO2 adduct. As peroxynitrite may be a mediator of neurotoxic process es, the obtained results suggest that neuromelanin may be important as a ph ysiological protector against peroxynitrite. (C) 2000 Elsevier Science B.V. All rights reserved.