The role of peroxiredoxin 6 in neutralization of X-ray mediated oxidative stress: effects on gene expression, preservation of radiosensitive tissues and postradiation survival of animals

Abstract

Peroxiredoxins are redox-sensing multifunctional enzymes, among them peroxiredoxin 6 (Prx6) can neutralize the most broadest range of hydroperoxides and play an important role in maintaining the redox homeostasis of the cell. In the present study, radioprotective and signaling regulatory effects of Prx6 were demonstrated and characterized. Intravenously administered exogenous Prx6 protects the organism of mice from the destructive action of ionizing radiation in the lethal dose range of 5–10 Gy. Dose reduction factor of 1.4 Prx6 injection reduces the severity of radiation-induced leuko- and thrombopenia in irradiated animals, also preventing the destruction of epithelial cells in the small intestine. Injecting exogenous Prx6 also as its mutated form of Prx6–C47S lacking peroxidase activity affects the expression of genes involved in antioxidant response, DNA reparation, apoptosis and inflammatory processes, in bone marrow cells both in intact animals and in those subjected to ionizing radiation. The radioprotective properties of Prx6 are based, on the one hand, on the capability for ROS neutralization, and on the other hand – on the potentiality for activation of reparation processes of the cell under oxidative stress conditions. Prx6 can be considered as a potentially perspective radioprotective agent for the reduction of risks from the damaging action of ionizing radiation on the mammalian organism.

Keywords:

• Peroxiredoxin
• antioxidant
• ionizing radiation
• radioprotection
• gene expression

Acknowledgements

The work was supported by the Russian Foundation for Basic Research (RFBR) (grant nos. 15-04-04021-a and 16-34-60017-mol_a_dk) and the “Molecular and Cell Biology” program of the Presidium of the Russian Academy of Sciences.

Disclosure statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Additional information

Funding

The work was supported by the Russian Foundation for Basic Research (RFBR) (grant nos. 15-04-04021-a and 16-34-60017-mol_a_dk) and the “Molecular and Cell Biology” program of the Presidium of the Russian Academy of Sciences.