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

Weidinger A, Kozlov AV - Biomolecules (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Donaueschingenstraße 13, 1200 Vienna, Austria. adelheid.weidinger@trauma.lbg.ac.at.

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.

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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.
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biomolecules-05-00472-f001: 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.

Mentions: We assume that whether RONS have a beneficial or deleterious effect is primarily defined by their quality, being primary or secondary RONS, and only secondly by their quantity (Figure 1). Therefore, we think that the common statement that at low concentrations ROS regulate physiological processes and at high concentrations are deleterious is not completely correct. Critical consideration of the existing literature shows that deleterious effects, termed as oxidative stress, do not appear if only one primary species is present in a biological system, even at high concentrations. To develop deleterious effects, a primary species reacts with another or a transition metal, yielding highly reactive secondary species, such as ONOO− or •OH. The secondary RONS are catalytically very active, not tightly controlled and consequently may not act as signal transducers. In contrast, primary RONS are well controlled; their reactions with targets are reversible; and they do not damage target molecules. This makes them ideal for intracellular signaling processes. Unfortunately, the majority of papers on signaling refers to RONS without specifying their types. In this review, we highlight an approach allowing one to distinguish the contribution of different RONS. This can be used to define the origin of RONS contributing to intracellular signaling cascades in future studies.


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

Weidinger A, Kozlov AV - Biomolecules (2015)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496681&req=5

biomolecules-05-00472-f001: 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.
Mentions: We assume that whether RONS have a beneficial or deleterious effect is primarily defined by their quality, being primary or secondary RONS, and only secondly by their quantity (Figure 1). Therefore, we think that the common statement that at low concentrations ROS regulate physiological processes and at high concentrations are deleterious is not completely correct. Critical consideration of the existing literature shows that deleterious effects, termed as oxidative stress, do not appear if only one primary species is present in a biological system, even at high concentrations. To develop deleterious effects, a primary species reacts with another or a transition metal, yielding highly reactive secondary species, such as ONOO− or •OH. The secondary RONS are catalytically very active, not tightly controlled and consequently may not act as signal transducers. In contrast, primary RONS are well controlled; their reactions with targets are reversible; and they do not damage target molecules. This makes them ideal for intracellular signaling processes. Unfortunately, the majority of papers on signaling refers to RONS without specifying their types. In this review, we highlight an approach allowing one to distinguish the contribution of different RONS. This can be used to define the origin of RONS contributing to intracellular signaling cascades in future studies.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Donaueschingenstraße 13, 1200 Vienna, Austria. adelheid.weidinger@trauma.lbg.ac.at.

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.

Show MeSH
Related in: MedlinePlus