Biological Activities of Reactive Oxygen and Nitrogen Species: Oxidative Stress versus Signal Transduction

Abstract

In the past, reactive oxygen and nitrogen species (RONS) were shown to cause oxidative damage to biomolecules, contributing to the development of a variety of diseases. However, recent evidence has suggested that intracellular RONS are an important component of intracellular signaling cascades. The aim of this review was to consolidate old and new ideas on the chemical, physiological and pathological role of RONS for a better understanding of their properties and specific activities. Critical consideration of the literature reveals that deleterious effects do not appear if only one primary species (superoxide radical, nitric oxide) is present in a biological system, even at high concentrations. The prerequisite of deleterious effects is the formation of highly reactive secondary species (hydroxyl radical, peroxynitrite), emerging exclusively upon reaction with another primary species or a transition metal. The secondary species are toxic, not well controlled, causing irreversible damage to all classes of biomolecules. In contrast, primary RONS are well controlled (superoxide dismutase, catalase), and their reactions with biomolecules are reversible, making them ideal for physiological/pathophysiological intracellular signaling. We assume that whether RONS have a signal transducing or damaging effect is primarily defined by their quality, being primary or secondary RONS, and only secondly by their quantity.

Figure 1

Scheme illustrating physiological and pathophysiological reactions of different reactive species. A, primary reactive species (NO^•, O₂^•−, Fe, ROOH) and the products of the interaction of two identical reactive species (dismutation of O₂ to H₂O₂) and transition metals (reactive oxygen, nitrogen and metal species = RONMS). B, secondary products of reactions between two different RONMS. Primary products predominantly contribute to physiological processes (e.g., signaling, protein synthesis); secondary products exert deleterious effects on diverse cell functions. Abbreviations: NO, nitric oxide; O₂^•−, superoxide; Fe, iron; ROOH, lipid peroxide; H₂O₂ hydrogen peroxide; RH, non-oxidized lipid; R^•, RO^•, ROO^•, lipid radicals; NOS, nitric oxide synthase; l-arg, l-arginine; ONOO⁻, peroxynitrite; NOX, NADPH oxidase; mito, mitochondria; SOD, superoxide dismutase; CAT, catalase; H₂O, water; Cl⁻, chloride ion; MPO, myeloperoxidase; HClO, hypochlorous acid; ^•OH, hydroxyl radical; UV, ultraviolet radiation.