Incubation of S-nitrosocysteine or S-nitrosoglutathione (5-100 M) in the presence of a generator of superoxide (xanthine/xanthine oxidase) resulted in a time-dependent decomposition of S-nitrosothiols and accumulation of nitrite/nitrate in reaction mixtures. Quantitatively, the amounts of nitrite/nitrate represented >90% of nitrosonium equivalent of S-nitrosothiols degraded during the incubation. The reaction rates were unaffected by the presence catalase (1 unit/ml). Kinetic analysis showed that the degradation of S-nitrosothiols in the presence of superoxide proceeded at second order rate constants of 76,900 M ؊1 s ؊1 (S-nitrosocysteine) and 12,800 M ؊1 s ؊1 (Snitrosoglutathione), respectively, with a stoichiometric ratio of 1 mol of S-nitrosothiol per 2 mol of superoxide. The findings provide the evidence for the involvement of superoxide in the metabolism of S-nitrosothiols. Furthermore, substantially slower reaction rates of superoxide with S-nitrosothiols relative to the reaction rate with NO are consistent with the contention that the transient formation of S-nitrosothiols in biological systems may protect NO from its rapid destruction by superoxide, thus enabling these compounds to serve as carriers or buffers of NO. S-Nitrosothiols (RSNOs)1 have been shown previously to elicit biochemical and physiological effects similar to those elicited by endothelium-derived relaxing factor, including stimulation of soluble guanylate cyclase, vascular relaxation, and inhibition of platelet aggregation (1-3). Such effects have been, for the most part, attributed to the release of NO or related reactive nitrogen oxide species. However, biochemical mechanism(s) leading to the dissociation of S-NO bond under in vivo conditions are at this time largely unknown. Under in vitro conditions, RSNOs are reasonably stable (over a period of several hours) in physiological buffers in the presence of a chelator of transition metals. The breakdown of S-NO bond can be induced by UV light (4) and certain metal ions such as Hg 2ϩ or Cu ϩ (5, 6); however, neither of these reactivities can be considered to be of physiological importance. Additional reactivities of RSNOs which may be operative under in vivo conditions include thiol-and glutathione peroxidase-mediated decomposition, respectively (7,8). Available evidence suggests that thiolmediated degradation of RSNOs results in the formation of nitroxyl anion rather than NO (9), whereas the reaction between RSNOs and glutathione peroxidase causes the deactivation of the enzyme due to the modification of selenocysteine residue at its active center (10).In this report, we present the evidence that RSNOs formed by low molecular weight biological thiols (L-cysteine and glutathione) are degraded in the presence of superoxide. Since the propensity for the generation of superoxide under aerobic conditions is a ubiquitous property of biological systems, the interaction of superoxide with RSNOs is likely to represent a biological route of RSNO catabolism which is not confined to specific tissues...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.