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Reactive Oxygen Species: Participation in Cellular Processes and Progression of Pathology

Abstract

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are not only side products of chemical reactions, but participants in various cellular processes as well. ROS and RNS are involved in the defense against pathogenic microorganisms (H2O2, HOCl, ONOO, \({\text{O}}_{2}^{{\centerdot - }},\) and OH), fertilization (H2O2), cell division \(\left( {{\text{O}}_{2}^{{\centerdot - }}} \right),\) apoptosis (H2O2), regeneration (H2O2), coordination of a direction of the cellular movement, regulation of the vascular tone (NO), etc. A balance between the production and the removal of ROS and RNS results in an intracellular homeostasis, whereas their overproduction causes cell damage and most probably leads to changes in the cellular metabolism. ROS and RNS can act as intracellular messengers, i.e., change the intracellular oxidative–reductive state and/or structure and function of a protein by means of a modification of amino acid residues (mainly cysteines), and the red-ox state of a number of proteins can affect the cellular metabolism. Hydrogen peroxide is the main form of ROS which participates in oxidative–reductive transduction of signals in eukaryotes. Alterations in antioxidant systems contribute to aging and a development of the age-related diseases. Primarily, aging is associated with an increased level of oxidative stress, various types of macromolecular changes, and an accumulation of DNA damage. Ageing can, to some extent, be a consequence of disorders in the proteostasis regulation and changes in the proteome functioning, because proteins are responsible for most of the cellular functions. Moreover, not all the cellular proteins can be resynthesized due to the age-related DNA damage. Thus, reactive oxygen and nitrogen species that are permanently generated in an organism are important participants in regulatory mechanisms in a cell, but also a reason for several pathological states, including cancers. ROSs are known to regulate the metabolism of signal molecules which are necessary for the cell cycle. Moreover, ROSs are able to change the activity of the iron-containing proteins. The aging that is associated with an ineffective functioning of the antioxidant defense is connected with the oxidative stress, various changes in cellular structures and macromolecules, an accumulation of metabolic products which can have a negative effect, the DNA damage (for example, owing to mistakes during a replication by DNA polymerases), and disorders in functioning of reparation systems.

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Correspondence to R. K. Kostin.

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Translated by L. Onoprienko

Abbreviations: DNA, deoxyribonucleic acid; 2dDR1P, 2-deoxy-D-riboso-1-phosphate; ERL, lumen of the endoplasmic reticulum; iNOS, inducible NO synthase; NOX, NADPH oxidase; Prx, peroxiredoxin; RNS, reactive nitrogen species; ROS, reactive oxygen species; SOD, superoxide dismutase; TP, thymidine phosphorylase; UPR, response of an unfolded protein.

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Shlapakova, T.I., Kostin, R.K. & Tyagunova, E.E. Reactive Oxygen Species: Participation in Cellular Processes and Progression of Pathology. Russ J Bioorg Chem 46, 657–674 (2020). https://doi.org/10.1134/S1068162020050222

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Keywords:

  • reactive oxygen species
  • reactive nitrogen species
  • antioxidant defense
  • intracellular messengers
  • redox signaling
  • hydrogen peroxide
  • superoxide anion
  • hydroxyl radical
  • hypochlorous acid
  • hypobromous acid
  • hypothiocyanic acid
  • peroxynitrite
  • nitric oxide
  • ferroptosis
  • iron-sulfur clusters
  • aging
  • antioxidants