Radioprotective Role of Peroxiredoxin 6

Abstract

Peroxiredoxin 6 (Prdx6) is a member of an evolutionary ancient family of peroxidase enzymes with diverse functions in the cell. Prdx6 is an important enzymatic antioxidant. It reduces a wide range of peroxide substrates in the cell, thus playing a leading role in the maintenance of the redox homeostasis in mammalian cells. Beside peroxidase activity, Prdx6 has been shown to possess an activity of phospholipase A2, an enzyme playing an important role in membrane phospholipid metabolism. Moreover, Prdx6 takes part in intercellular and intracellular signal transduction due to its peroxidase and phospholipase activity, thus facilitating the initiation of regenerative processes in the cell, suppression of apoptosis, and activation of cell proliferation. Being an effective and important antioxidant enzyme, Prdx6 plays an essential role in neutralizing oxidative stress caused by various factors, including action of ionizing radiation. Endogenous Prdx6 has been shown to possess a significant radioprotective potential in cellular and animal models. Moreover, intravenous infusion of recombinant Prdx6 to animals before irradiation at lethal or sublethal doses has shown its high radioprotective effect. Exogenous Prdx6 effectively alleviates the severeness of radiation lesions, providing normalization of the functional state of radiosensitive organs and tissues, and leads to a significant elevation of the survival rate of animals. Prdx6 can be considered as a potent and promising radioprotective agent for reducing the pathological effect of ionizing radiation on mammalian organisms. The radioprotective properties and mechanisms of radioprotective action of Prdx6 are discussed in the current review.

Prdx6 Plays a Main Role in the Crosstalk between Aging and Metabolic Sarcopenia

“…Accordingly, Prdx6 levels were inversely correlated with cellular aging; a decline of Prdx6 expression, indeed, was reported in aged ocular cells [11]. It is important to remark that the subcellular localization of Prdx6 is crucial for its enzymatic activities [12]. Prdx6 has higher phospholipase A2 activity at an acidic pH, and higher peroxidase activity at a neutral pH [12].…”

“…It is important to remark that the subcellular localization of Prdx6 is crucial for its enzymatic activities [12]. Prdx6 has higher phospholipase A2 activity at an acidic pH, and higher peroxidase activity at a neutral pH [12]. Moreover, Prdx6 from the cytosol and lysosomal-type organelles can move to the mitochondria and cellular membrane, by controlling cellular oxidative stress status [12].…”

“…Prdx6 has higher phospholipase A2 activity at an acidic pH, and higher peroxidase activity at a neutral pH [12]. Moreover, Prdx6 from the cytosol and lysosomal-type organelles can move to the mitochondria and cellular membrane, by controlling cellular oxidative stress status [12]. All these Prdx6 functions may be influenced by cellular redox state that may change across aging and other metabolic variations.…”

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

“…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.…”

Antioxidants Special Issue: Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family

“…One of those pathologies, Fuchs endothelial corneal dystrophy (FECD), is a leading indication for corneal endothelial transplantation as described in the subsequent article by Lovatt et al; this report of original research is focused on the role of Prdx6 in the preservation of corneal endothelial cellular integrity [27]. The ninth article by Sharapov et al reviews the ability of Prdx6 to protect against X-irradiation-induced injury such as that used for treatment of cancer [28]. Both exogenous Prdx6 as well as increased expression of endogenous Prdx6 provide radioprotection.…”