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Exogenous 8-oxo-7,8-dihydro-2′-deoxyguanosine: Biomedical properties, mechanisms of action, and therapeutic potential

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Abstract

Abstract—8-Oxo-7,8-dihydroguanine (8-oxo-G) is a key biomarker of oxidative damage to DNA in cells, and its genotox- icity is well-studied. In recent years, it has been confirmed experimentally that free 8-oxo-G and molecules containing it are not merely inert products of DNA repair or degradation, but they are actively involved in intracellular signaling. In this review, data are systematized indicating that free 8-oxo-G and oxidized (containing 8-oxo-G) extracellular DNA function in the body as mediators of stress signaling and initiate inflammatory and immune responses to maintain homeostasis under the action of external pathogens, whereas exogenous 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGuo) exhibits pro- nounced antiinflammatory and antioxidant properties. This review describes known action mechanisms of oxidized guanine and 8-oxo-G-containing molecules. Prospects for their use as a therapeutic target are considered, as well as a pharmaceu- tical agent for treatment of a wide range of diseases whose pathogenesis is significantly contributed to by inflammation and oxidative stress.

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Abbreviations

A:

adenine

BER:

base excision repair

DAMP:

damage-associated molecular patterns

ecDNA:

extracellular DNA; G, guanine

MAPK:

mitogen-activated protein kinases

OGG1:

8-oxoguanine-DNA-glycosylase 1

8-oxo-dGuo:

8-oxo-7,8-dihydro-2'-deoxyguanosine (8-hydroxydeoxyguano-sine)

8-oxo-G:

8-oxo-7,8-dihydroguanine (8-hydroxygua-nine)

8-oxo-Guo:

8-oxo-7,8-dihydroguanosine (8-hydroxy-guanosine)

RNS:

reactive nitrogen species

ROS:

reactive oxy- gen species

TLR:

Toll-like receptors

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Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142292, Pushchino, Moscow Region, Russia

    A. V. Chernikov, A. M. Usacheva & V. I. Bruskov

  2. Moscow Regional Research and Clinical Institute (MONIKI), 129110, Moscow, Russia

    S. V. Gudkov

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

    S. V. Gudkov

  4. Lobachevsky State University of Nizhnii Novgorod, 603950, Nizhnii Novgorod, Russia

    S. V. Gudkov

  5. Pushchino State Research Institute for Natural Sciences, 142290 Pushchino, Moscow Region, Russia

    V. I. Bruskov

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Original Russian Text © A. V. Chernikov, S. V. Gudkov, A. M. Usacheva, V. I. Bruskov, 2017, published in Uspekhi Biologicheskoi Khimii, 2017, Vol. 57, pp. 267-302.

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Chernikov, A.V., Gudkov, S.V., Usacheva, A.M. et al. Exogenous 8-oxo-7,8-dihydro-2′-deoxyguanosine: Biomedical properties, mechanisms of action, and therapeutic potential. Biochemistry Moscow 82, 1686–1701 (2017). https://doi.org/10.1134/S0006297917130089

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