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Dual Character of Reactive Oxygen, Nitrogen, and Halogen Species: Endogenous Sources, Interconversions and Neutralization

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Abstract

Oxidative stress resulting from accumulation of reactive oxygen, nitrogen, and halogen species (ROS, RNS, and RHS, respectively) causes the damage of cells and biomolecules. However, over the long evolutionary time, living organisms have developed the mechanisms for adaptation to oxidative stress conditions including the activity of the antioxidant system (AOS), which maintains low intracellular levels of RONS (ROS and RNS) and RHS. Moreover, living organisms have adapted to use low concentrations of these electrophiles for the regulation of cell functions through the reversible posttrans lational chemical modifications of redoxsensitive amino acid residues in intracellular effectors of signal transduction path ways (protein kinases and protein phosphatases), transcription factors, etc. An important finetuning mechanism that ensures involvement of RONS and RHS in the regulation of physiological processes is interconversion between different reactive species. This review focuses on the complex networks of interacting RONS and RHS types and their endogenous sources, such as NOX family of NADPH oxidases, complexes I and III of the mitochondrial electron transport chain, NO synthases, cytochrome P450 containing monooxygenase system, xanthine oxidoreductase, and myeloperoxidases. We high light that kinetic parameters of reactions involving RONS and RHS determine the effects of these reactive species on cell functions. We also describe the functioning of enzymatic and nonenzymatic AOS components and the mechanisms of RONS and RHS scavenging under physiological conditions. We believe that analysis of interactions between RONS and relationships between different endogenous sources of these compounds will contribute to better understanding of their role in the maintenance of cell redox homeostasis as well as initiation and progression of diseases.

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Abbreviations

COX:

cyclooxygenase or prostaglandin G/H synthase

CYP:

cytochrome P450

ETC:

electron transport chain

GPx:

glutathione peroxidase

GR:

glutathione reductase

GSH:

reduced glutathione

LOX:

lipoxygenase

NOS:

nitric oxide synthase

NOX:

proteins

NADPH:

oxidase family proteins

Prx:

peroxiredoxin

RHS:

reactive halogen species

RNS:

reactive nitrogen species

RONS:

reactive oxygen and nitrogen species

ROS:

reactive oxygen species

SOD:

superoxide dismutase

Srx:

sulfiredoxin

Trx:

thioredoxin

TrxR:

thioredoxin reductase

XOR:

xanthine oxidoreductase

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Funding The work was supported by I. M. Sechenov First Moscow State Medical University Strategic Development Program under the Russian Academic Excellence 5100 Project.

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Russian Text © The Author(s), 2020, published in Uspekhi Biologicheskoi Khimii, 2020, Vol. 60, pp. 123–172.

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Moldogazieva, N.T., Mokhosoev, I.M., Mel’nikova, T.I. et al. Dual Character of Reactive Oxygen, Nitrogen, and Halogen Species: Endogenous Sources, Interconversions and Neutralization. Biochemistry Moscow 85 (Suppl 1), 56–78 (2020). https://doi.org/10.1134/S0006297920140047

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