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.

Highlights

  • Reactive oxygen and nitrogen species (RONS) include two classes of chemically-reactive molecules containing oxygen and nitrogen

  • We showed that O2 can be released from mitochondria by using O2-sensitive spin probes and electron spin resonance spectroscopy [67]

  • Brunelle et al [72] demonstrated that overexpressing glutathione peroxidase or catalase, but not superoxide dismutase (SOD), stabilized hypoxia-inducible factor (HIF)-1 in cells, suggesting that H2O2 acts as signaling molecule in the process of HIF-1 regulation

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Summary

Introduction

Reactive oxygen and nitrogen species (RONS) include two classes of chemically-reactive molecules containing oxygen (reactive oxygen species, ROS) and nitrogen (reactive nitrogen species, RNS). Intracellular RONS, as well as excessive release of extracellular RONS were thought to induce deleterious effects, causing oxidative damage to different kinds of biomolecules. These processes are referred to as “oxidative stress”. More and more evidence suggest that intracellular generation of RONS is an important component of intracellular signaling cascades regulating several physiological functions, such as regulation of vascular tone, insulin synthesis, activation of hypoxia-inducible factor (HIF), cell proliferation, differentiation and migration It took over 50 years for a clear understanding of the chemical basis of free radical/RONS biology to emerge. This review is predominantly based on selected reviews, elaborating on different aspects of RONS activity and thought to be a guide through a large body of literature existing on this topic

Chemical Basics
Oxidative Stress
Signaling
Superoxide Radical
Hydrogen Peroxide
Secondary RONS
Conclusions

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