Dopamine-melanin protects against tyrosine nitration, tryptophan oxidation and Ca(2+)-ATPase inactivation induced by peroxynitrite.
The effects of dopamine-melanin (DA-melanin), a synthetic model of neuromelanin, on peroxynitrite-mediated 3-nitrotyrosine formation, oxidation of tryptophan 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 tryptophan residues and Ca(2+)-ATPase inactivation by peroxynitrite in a dose dependent manner. In the presence of bicarbonate, this inhibitory effect was lower for nitration and insignificant for oxidative protein modifications. These results suggest that neuromelanin can protect against nitrating and oxidizing action of peroxynitrite but is a worse protector against the peroxynitrite-CO(2) adduct. As peroxynitrite may be a mediator of neurotoxic processes, the obtained results suggest that neuromelanin may be important as a physiological protector against 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
Zajdel
A
A
Wilczok
A
A
Wilczok
T
T
Grzelak
A
A
Mateja
A
A
Soszyński
M
M
Bartosz
G
G
D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000097:blood*; D002417:Cattle; D004910:Erythrocyte Membrane / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D008543:Melanins / Q000737:chemistry* / Q000494:pharmacology*; D009566:Nitrates / Q000737:chemistry / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000187:drug effects; D014364:Tryptophan / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry*
D000975:Antioxidants; D008543:Melanins; D009566:Nitrates; D016877:Oxidants; C081789:dopamine melanin; C039642:peroxynitric acid; D012710:Serum Albumin, Bovine; D014443:Tyrosine; D014364:Tryptophan; D000252:Calcium-Transporting ATPases