Nitroglycerin (NTG) is an important cardiovascular agent, but tolerance during continuous administration limits its clinical utility. Increased vascular superoxide production may mediate nitrate tolerance via a reduction in nitric oxide availability. Because superoxide anion and nitric oxide react avidly to form peroxynitrite, an aggressive cellular toxicant that nitrates protein tyrosine resid...

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) play crucial roles in diabetic angiopathy. In vivo, however, the following facts remain unknown: whether COX-2 and iNOS bind, how peroxynitrite-induced nitration of COX-2 and iNOS affects their binding if they do bind, and what effects of it contribute to diabetic angiopathy. This study focused on the issues above. Diabetes was...

The inhibitory effects of various endogenous and synthetic compounds on the nitration and oxidation of L-tyrosine by peroxynitrite were examined. Nitrating and oxidizing activities were monitored by the formation of 3-nitrotyrosine and dityrosine with a HPLC-UV-fluorescence detector system, respectively. Glutathione, serotonin and synthetic sulfur- and selenium-containing compounds inhibited bo...

In the present study, we investigated how cytochrome c catalyzed the nitration of tyrosine at various pHs. The cytochrome c-catalyzed nitration of tyrosine occurred in proportion to the concentration of hydrogen peroxide, nitrite or cytochrome c. The cytochrome c-catalyzed nitration of tyrosine was inhibited by catalase, sodium azide, cystein, and uric acid. These results show that the cytochro...

There has been some dispute regarding reaction products formed at physiological peroxynitrite fluxes in the nanomolar range with phenolic molecules, when used to predict the behavior of protein-bound aromatic amino acids like tyrosine. Previous data showed that at nanomolar fluxes of peroxynitrite, nitration of these phenolic compounds was outcompeted by dimerization (e.g. biphenols or dityrosi...

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) play crucial roles in diabetic angiopathy. In vivo, however, the following facts remain unknown: whether COX-2 and iNOS bind, how peroxynitrite-induced nitration of COX-2 and iNOS affects their binding if they do bind and what effects of this mechanism contribute to diabetic angiopathy. This study focused on the issues above. D...

Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme in the biosynthesis of dopamine (DA). TH activity is significantly diminished in Parkinson's disease (PD) and by the neurotoxic amphetamines, thereby accentuating the reductions in DA associated with these conditions. Reactive oxygen and nitrogen species have been implicated in the damage to DA neurons seen in PD and in reaction ...

Chemokines promote leukocyte recruitment during inflammation. The oxidative burst is an important effector mechanism, this leads to the generation of reactive nitrogen species (RNS), including peroxynitrite (ONOO). The current study was performed to determine the potential for nitration to alter the chemical and biological properties of the prototypical CC chemokine, CCL2. Immunofluorescence wa...

The pH dependence of the rate of glutamate oxidation by bovine liver glutamate dehydrogenase has been determined in the absence and presence of allosteric modifiers. In the range of pH 7 to 9 where the enzyme was saturated by substrate, the degree of activation by ADP or inhibition by GTP did not vary substantially with pH. The pH dependence of chicken liver glutamate dehydrogenase measured in ...

BACKGROUND We revealed in previous studies that nitration of food proteins reduces the risk of de novo sensitization in a murine food allergy model. In contrast, in situations with preformed specific IgE antibodies, in vitro experiments suggested an increased capacity of effector cell activation by nitrated food proteins. OBJECTIVE The aim of this study was to investigate the influence of pro...