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Hydroperoxide-Reducing Enzymes in the Regulation of Free-Radical Processes

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Abstract

The review presents current concepts of the molecular mechanisms of oxidative stress development and describes main stages of the free-radical reactions in oxidative stress. Endogenous and exogenous factors of the oxidative stress development, including dysfunction of cell oxidoreductase systems, as well as the effects of various external physicochemical factors, are discussed. The review also describes the main components of the antioxidant defense system and stages of its evolution, with a special focus on peroxiredoxins, glutathione peroxidases, and glutathione S-transferases, which share some phylogenetic, structural, and catalytic properties. The substrate specificity, as well as the similarities and differences in the catalytic mechanisms of these enzymes, are discussed in detail. The role of peroxiredoxins, glutathione peroxidases, and glutathione S-transferases in the regulation of hydroperoxide-mediated intracellular and intercellular signaling and interactions of these enzymes with receptors and non-receptor proteins are described. An important contribution of hydroperoxide-reducing enzymes to the antioxidant protection and regulation of such cell processes as growth, differentiation, and apoptosis is demonstrated.

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Abbreviations

CP :

peroxidatic cysteine

CR :

resolving cysteine

Grx:

glutaredoxin

GPx:

glutathione peroxidase

GR:

glutathione reductase

GSH:

glutathione, reduced

HO• :

hydroxyl radical

In• :

antioxidant free radical

L• :

lipid alkyl radical

LH:

polyunsaturated fatty acid

LO• :

lipoxal radical

LOO• :

lipoperoxy radical

LOOH:

lipid hydroperoxide

RHS:

reactive halogen species

ROS:

reactive oxygen species

RNS:

reactive nitrogen species

LPO:

lipid peroxidation

O2 •− :

superoxide anion radical

GST:

glutathione S-transferase

PDI:

protein disulfide isomerase

Prx:

peroxiredoxin

RO• :

alkoxy radical

SOD:

superoxide dismutase

Trx:

thioredoxin

TrxR:

thioredoxin reductase

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Acknowledgments

The authors express their gratitude to Dr. V. I. Novoselov for his invaluable comments on the manuscript.

Funding

This work was supported by the Russian Foundation for Basic Research (project no. 20-14-50114).

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Mars G. Sharapov

  2. Prokhorov Institute of General Physics, Russian Academy of Sciences, 119991, Moscow, Russia

    Sergey V. Gudkov

  3. Lobachevsky State University of Nizhny Novgorod, 603022, Nizhny Novgorod, Russia

    Sergey V. Gudkov

  4. All-Russian Research Institute of Phytopathology, 143050, Bolshiye Vyazemy, Russia

    Sergey V. Gudkov

  5. National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, 121552, Moscow, Russia

    Vadim Z. Lankin

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  1. Mars G. Sharapov
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Correspondence to Mars G. Sharapov.

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Sharapov, M.G., Gudkov, S.V. & Lankin, V.Z. Hydroperoxide-Reducing Enzymes in the Regulation of Free-Radical Processes. Biochemistry Moscow 86, 1256–1274 (2021). https://doi.org/10.1134/S0006297921100084

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