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.

Comparative Study of Protective Action of Exogenous 2-Cys Peroxiredoxins (Prx1 and Prx2) Under Renal Ischemia-Reperfusion Injury

“…Previously, it has been shown that Prx1, Prx2, Prx5 and Prx6 are potent DAMPs in ischemic stroke, with TLR4 being their main recognition receptor. Through interaction with the TLR4 receptor, peroxiredoxins (Prx1, Prx2, Prx5 and Prx6) express pro-inflammatory/regenerative factors via the TLR4/MyD88/NF-kB signaling pathway [ 14 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. Moreover, we suggest that intravenous injection of recombinant Prx1 or Prx2 in animals before renal I/R injury can provide a preconditioning effect, through stimulation of the TLR4/NF-kB signaling pathway.…”

“…To test the therapeutic effect of exogenous Prx1 and Prx2 proteins, the solution of the corresponding recombinant protein was injected into the tail vein to a final concentration of 20 μg/g of bodyweight 15 min before the beginning of ischemia. Selection of the injection method and the concentrations of protein solutions was carried out according to previous studies [ 13 , 14 ].…”

“…It must be noted that some Prx representatives have been investigated previously in models of artificially induced oxidative stress: total irradiation, renal ischemia-reperfusion injury, small intestine, etc. [ 13 , 14 , 15 , 16 , 17 ]. It is the Prx family proteins that have shown high efficiency in oxidative stress neutralization, which is associated with the high antioxidant activity of these enzymes and a wide range of neutralizable hydroperoxides, both organic and inorganic in nature.…”

Peroxiredoxin 6 Attenuates Alloxan-Induced Type 1 Diabetes Mellitus in Mice and Cytokine-Induced Cytotoxicity in RIN-m5F Beta Cells

“…Recombinant proteins harbored His-tag, so the enzymes were purified by affinity chromatography on Ni-NTA-agarose (Thermo Fisher Scientific, USA), according to the manufacturer's recommendations. The technique of protein isolation was described earlier [23]. According to electrophoresis in 12% SDS-PAAG, the purity of the obtained enzymes was at least 98%.…”

Approximation of new generation pharmacological enzyme researches to clinical practice

“…Кардиопротекторный эффект подтверждался нормализацией частоты сердечных сокращений, поддержанием контрактильной функции миокарда и предупреждением губительного действия окислительного стресса. Благодаря снижению уровня окисли-тельного стресса у мышей (индуцированного ионизирующим излучением в летальных дозах 5-10 Гр) посредством внутривенного введения экзогенного пероксиредоксина-6 был продемонстрирован радиопротекторный эффект [48]. Значение фактора изменения дозы составило 1,45.…”