Sharapov Mars G, Novoselov Vladimir I, Gudkov Sergey V
Laboratory of Mechanisms of Reception, Institute of Cell Biophysics of the Russian Academy of Sciences, 142290 Pushchino, Russia.
Wave Research Center, Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia.
Antioxidants (Basel). 2019 Jan 5;8(1):15. doi: 10.3390/antiox8010015.
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.
过氧化物酶体增殖物激活受体6(Prdx6)是过氧化物酶家族中一个进化古老的成员,在细胞中具有多种功能。Prdx6是一种重要的酶促抗氧化剂。它能还原细胞内多种过氧化物底物,从而在维持哺乳动物细胞氧化还原稳态中起主导作用。除过氧化物酶活性外,Prdx6还被证明具有磷脂酶A2活性,该酶在膜磷脂代谢中起重要作用。此外,Prdx6因其过氧化物酶和磷脂酶活性参与细胞间和细胞内信号转导,从而促进细胞再生过程的启动、抑制细胞凋亡并激活细胞增殖。作为一种有效且重要的抗氧化酶,Prdx6在中和包括电离辐射作用在内的各种因素引起的氧化应激中起关键作用。内源性Prdx6已在细胞和动物模型中显示出显著的辐射防护潜力。此外,在以致死或亚致死剂量照射动物前静脉注射重组Prdx6已显示出其高度的辐射防护作用。外源性Prdx6有效减轻辐射损伤的严重程度,使放射敏感器官和组织的功能状态恢复正常,并导致动物存活率显著提高。Prdx6可被视为一种有效且有前景的辐射防护剂,用于减轻电离辐射对哺乳动物机体的病理影响。本综述讨论了Prdx6的辐射防护特性及辐射防护作用机制。