Novel Effects of Nitric Oxide

Abstract

Nitric oxide (NO), a simple free radical gas, elicits a surprisingly wide range of physiological and pathophysiological effects. NO interacts with soluble guanylate cyclase to evoke many of these effects. However, NO can also interact with molecular oxygen and superoxide radicals to produce reactive nitrogen species that can modify a number of macromolecules including proteins, lipids, and nucleic acids. NO can also interact directly with transition metals. Here, we have reviewed the non--3',5'-cyclic-guanosine-monophosphate-mediated effects of NO including modifications of proteins, lipids, and nucleic acids.

Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping

“…in the experiments with continuous excitation should be orders of magnitude lower than in our laser flash photolysis experiments, and thus the hydration of guanine radicals can compete with their combination reactions with superoxide radicals. Biological Implications-In biological systems, superoxide radicals are generated in mitochondria and by neutrophils and macrophages (58). Mitochondria produce superoxide during aerobic respiration, a phenomenon that is significantly enhanced during oxidative stress developed in response to various diseases.…”

Ammonia elimination from protonated nucleobases and related synthetic substrates

“…This chemistry has been studied extensively because of the dietary and environmental exposure of humans to these substances [3][4][5]. Toxicological studies of deamination became more significant when it was recognized that endogenous nitric oxide [6,7] causes nitrosation [8,9], and that this process is accelerated by chronic inflammatory diseases [10,11]. It has been known for a long time that deamination of adenine 1, guanine 2, and cytosine 3 (Scheme 1) results in the formation of hypoxanthine, xanthine, and uracil, respectively, and these products are thought to result from DNA base diazonium ions 4-6, respectively, by direct nucleophilic dediazoniation.…”

Histone H1.2 is a substrate for denitrase, an activity that reduces nitrotyrosine immunoreactivity in proteins

“…Although many effects of NO are mediated through its direct interaction with guanylyl cyclase activation (1)(2)(3)(4)(5)(6)(7)(8), its indirect action via secondary reactions with reactive oxygen species, forming reactive nitrogen species accounts for other effects. The reaction of NO and its reactive intermediates with protein bound tyrosine residues causes nitrotyrosine formation (9). Several mechanisms for nitrotyrosine formation have been suggested that involve peroxynitrite or myeloperoxidase (10).…”