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

N. T. Moldogazieva1,a*, I. M. Mokhosoev2,b*, T. I. Mel’nikova1, S. P. Zavadskiy1, A. N. Kuz’menko1, and A. A. Terentiev2

1Sechenov First Moscow State Medical University, 119991 Moscow, Russia

2Pirogov Russian National Research Medical University, 117997 Moscow, Russia

* To whom correspondence should be addressed.

Received July 31, 2019; Revised August 6, 2019; Accepted August 9, 2019
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 post-translational chemical modifications of redox-sensitive amino acid residues in intracellular effectors of signal transduction pathways (protein kinases and protein phosphatases), transcription factors, etc. An important fine-tuning 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 highlight 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 non-enzymatic 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.
KEY WORDS: ROS, RNS, RHS, antioxidant system, NADPH oxidases, electron transport chain, NO synthases, CYP-containing monooxygenase system, xanthine oxidoreductase, heme-containing peroxidases

DOI: 10.1134/S0006297920140047