title: 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.
authors.affiliation: a Institute of Cell Biophysics , Russian Academy of Sciences , Moscow , Russia.
authors.forename: M G
authors.initials: MG
authors.lastname: Sharapov
authors.affiliation: a Institute of Cell Biophysics , Russian Academy of Sciences , Moscow , Russia.
authors.forename: V I
authors.initials: VI
authors.lastname: Novoselov
authors.affiliation: a Institute of Cell Biophysics , Russian Academy of Sciences , Moscow , Russia.
authors.forename: E E
authors.initials: EE
authors.lastname: Fesenko
authors.affiliation: b Institute of Theoretical and Experimental Biophysics , Russian Academy of Sciences , Moscow , Russia.
authors.forename: V I
authors.initials: VI
authors.lastname: Bruskov
authors.affiliation: c A.M. Prokhorov General Physics Institute , Russian Academy of Sciences , Moscow , Russia.|d Lobachevsky State University of Nizhni Novgorod , Nizhni Novgorod , Russia.
authors.forename: S V
authors.initials: SV
authors.lastname: Gudkov
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D054465:Peroxiredoxin VI / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D015996:Survival Rate; D014965:X-Rays
chemical_list: D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D054465:Peroxiredoxin VI
keywords: Peroxiredoxin; antioxidant; gene expression; ionizing radiation; radioprotection