TY - JOUR
T1 - Inhibition of peroxynitrite-mediated tyrosine nitration by a novel pyrrolopyrimidine antioxidant
AU - Rohn, Troy T.
AU - Quinn, Mark T.
PY - 1998/7/24
Y1 - 1998/7/24
N2 - Peroxynitrite is a cytotoxic, free radical species that is formed by the combination of superoxide and nitric oxide. The goal of the present study was to examine the ability of a novel antioxidant, U-101033E, to prevent peroxynitrite-mediated oxidative damage of red blood cell membrane proteins. Treatment of red blood cell membranes with peroxynitrite resulted in oxidative damage as evidenced by the presence of both membrane protein cross-linking and nitration of tyrosine residues. Membrane protein cross-linking was the result of oxidation of sulfhydryl groups and was completely blocked by the addition of dithiothreitol. Dithiothreitol also prevented peroxynitrite-mediated nitration of tyrosine red blood cell proteins. U-101033E prevented nitrotyrosine formation in peroxynitrite-treated red blood cell membrane proteins in a concentration-dependent manner, with maximal protection observed at 100 μM U-101033E. However, at a similar concentration where U-101033E prevented tyrosine nitration, it had little or no effect on membrane protein cross-linking. Our results suggest that U-101033E may be intercepting a peroxynitrite-derived reactive nitrogen species that is capable of nitrating tyrosine residues. The ability of U-101033E to prevent tyrosine nitration by peroxynitrite represents a new role for this class of antioxidants and suggests that the pyrrolopyrimidines may be useful in the treatment of diseases where peroxynitrite-mediated injury is implicated. Copyright (C) 1998 Elsevier Science B.V.
AB - Peroxynitrite is a cytotoxic, free radical species that is formed by the combination of superoxide and nitric oxide. The goal of the present study was to examine the ability of a novel antioxidant, U-101033E, to prevent peroxynitrite-mediated oxidative damage of red blood cell membrane proteins. Treatment of red blood cell membranes with peroxynitrite resulted in oxidative damage as evidenced by the presence of both membrane protein cross-linking and nitration of tyrosine residues. Membrane protein cross-linking was the result of oxidation of sulfhydryl groups and was completely blocked by the addition of dithiothreitol. Dithiothreitol also prevented peroxynitrite-mediated nitration of tyrosine red blood cell proteins. U-101033E prevented nitrotyrosine formation in peroxynitrite-treated red blood cell membrane proteins in a concentration-dependent manner, with maximal protection observed at 100 μM U-101033E. However, at a similar concentration where U-101033E prevented tyrosine nitration, it had little or no effect on membrane protein cross-linking. Our results suggest that U-101033E may be intercepting a peroxynitrite-derived reactive nitrogen species that is capable of nitrating tyrosine residues. The ability of U-101033E to prevent tyrosine nitration by peroxynitrite represents a new role for this class of antioxidants and suggests that the pyrrolopyrimidines may be useful in the treatment of diseases where peroxynitrite-mediated injury is implicated. Copyright (C) 1998 Elsevier Science B.V.
KW - Antioxidant
KW - Peroxynitrite
KW - Pyrrolopyrimidine
KW - Tyrosine nitration
UR - http://www.scopus.com/inward/record.url?scp=0032563268&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(98)00399-9
DO - 10.1016/S0014-2999(98)00399-9
M3 - Article
C2 - 9726663
AN - SCOPUS:0032563268
SN - 0014-2999
VL - 353
SP - 329
EP - 336
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -