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Effect of Peroxiredoxin 6 on p53 Transcription Factor Level

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Abstract

Peroxiredoxin 6 (Prdx6) is an important antioxidant enzyme with multiple functions in the cell. Prdx6 neutralizes a wide range of hydroperoxides, participates in phospholipid metabolism and cell membrane repair, and in transmission of intracellular and intercellular signals. Disruption of normal Prdx6 expression in the cell leads to the development of pathological conditions. Decrease in the Prdx6 concentration leads to increase in oxidative damage to the cell. At the same time, hyperproduction of Prdx6 is associated with increase in antioxidant status, suppression of apoptosis, and carcinogenesis. Currently, mechanisms of carcinogenic action of peroxiredoxins are poorly understood. In this work we established that the 3-4-fold increase in Prdx6 production in mouse embryonic fibroblast 3T3 cells leads to the 4-5-fold decrease in the level of oncosuppressor p53. At the same time, hyperproduction of Prdx6 leads to the increased expression of RELA and HIF1A, which have oncogenic effects. The 3-4-fold increase in intracellular Prdx6 increases intensity of cell proliferation by 20-30%, promotes increase in antioxidant activity by 30-50%, and increases radioresistance of the transfected 3T3 cells by 30-40%. Increase of the level of intranuclear Prdx6 leads to the decrease in expression of the DNA repair genes in response to radiation, indicating decrease in the genomic DNA damage. This work discusses possible molecular mechanisms of p53 suppression during Prdx6 hyperproduction, which could be used in the development of new approaches in cancer therapy.

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Abbreviations

AP-1:

Activating Protein-1

carboxy-H2DCFDA:

6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate

GFP:

green fluorescent protein

HIF-1α:

hypoxia-inducible factor 1-alpha

NF-κB:

nuclear factor kappa-light-chain-enhancer of activated B cells

Nrf2:

nuclear factor erythroid 2-related factor 2

p53:

transcription factor

Prdx:

peroxiredoxin

ROS:

reactive oxygen species

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Acknowledgments

Equipment of the Center for Collective Use of the Center of Biological Studies, Russian Academy of Sciences was used: department of optical microscopy and spectrophotometry (Leica TCS SP-5, Leica, Germany), department of the sources of ionizing radiation (RUT-15, Mosrentgen, Russia). Part of the study was carried out using a microplate reader (Infinite 200, Tecan, Austria) from the Center for Collective Use of the Institute of Experimental Biology, Russian Academy of Sciences.

Funding

This work was financially supported by the Russian Foundation for Basic Research (project no. 20-015-00216A).

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Authors and Affiliations

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

    Mars G. Sharapov, Ruslan G. Goncharov, Svetlana B. Parfenyuk & Olga V. Glushkova

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  1. Mars G. Sharapov
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  2. Ruslan G. Goncharov
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  3. Svetlana B. Parfenyuk
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Contributions

M. G. Sharapov, O. V. Glushkova – concept of the study and supervision; M. G. Sharapov, R. G. Goncharov, S. B. Parfenyuk, O. V. Glushkova – conducting experiments and discussion of results; M. G. Sharapov – writing the paper; O. V. Glushkova – editing the paper.

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Correspondence to Mars G. Sharapov.

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The authors declare no conflicts of interest in financial or any other sphere. This article does not contain any studies with human participants or animals performed by any of the authors.

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Sharapov, M.G., Goncharov, R.G., Parfenyuk, S.B. et al. Effect of Peroxiredoxin 6 on p53 Transcription Factor Level. Biochemistry Moscow 87, 839–849 (2022). https://doi.org/10.1134/S0006297922080156

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