The Experts below are selected from a list of 1590 Experts worldwide ranked by ideXlab platform

Aron B Fisher - One of the best experts on this subject based on the ideXlab platform.

  • genetic inactivation of the phospholipase a2 activity of Peroxiredoxin 6 in mice protects against lps induced acute lung injury
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2019
    Co-Authors: Sheldon I Feinstein, Elena M Sorokina, Jose Pablo Vazquezmedina, Priyal Patel, Renata Bannitzfernandes, Chandra Dodia, Shampa Chatterjee, Aron B Fisher
    Abstract:

    Peroxiredoxin 6 (Prdx6) is a multifunctional enzyme that serves important antioxidant roles by scavenging hydroperoxides and reducing peroxidized cell membranes. Prdx6 also plays a key role in cell...

  • hyperoxidation of Peroxiredoxin 6 induces alteration from dimeric to oligomeric state
    Antioxidants, 2019
    Co-Authors: Sharifun Shahnaj, Aron B Fisher, Rimpy Kaur Chowhan, Laishram Rajendrakumar Singh, Potshangbam Angamba Meetei, Pushpa Kakchingtabam, Khundrakpam Herojit Singh, Potshangbam Nongdam, Hamidur Rahaman
    Abstract:

    Peroxiredoxins(Prdx), the family of non-selenium glutathione peroxidases, are important antioxidant enzymes that defend our system from the toxic reactive oxygen species (ROS). They are thiol-based peroxidases that utilize self-oxidation of their peroxidatic cysteine (Cp) group to reduce peroxides and peroxidized biomolecules. However, because of its high affinity for hydrogen peroxide this peroxidatic cysteine moiety is extremely susceptible to hyperoxidation, forming peroxidase inactive sulfinic acid (Cys-SO2H) and sulfonic acid (Cys-SO3H) derivatives. With the exception of Peroxiredoxin 6 (Prdx6), hyperoxidized sulfinic forms of Prdx can be reversed to restore peroxidase activity by the ATP-dependent enzyme sulfiredoxin. Interestingly, hyperoxidized Prdx6 protein seems to have physiological significance as hyperoxidation has been reported to dramatically upregulate its calcium independent phospholipase A2 activity. Using biochemical studies and molecular dynamic (MD) simulation, we investigated the roles of thermodynamic, structural and internal flexibility of Prdx6 to comprehend the structural alteration of the protein in the oxidized state. We observed the loosening of the hydrophobic core of the enzyme in its secondary and tertiary structures. These changes do not affect the internal dynamics of the protein (as indicated by root-mean-square deviation, RMSD and root mean square fluctuation, RMSF plots). Native-PAGE and dynamic light scattering experiments revealed the formation of higher oligomers of Prdx6 under hyperoxidation. Our study demonstrates that post translational modification (like hyperoxidation) in Prdx6 can result in major alterations of its multimeric status.

  • the phospholipase a2 activity of Peroxiredoxin 6
    Journal of Lipid Research, 2018
    Co-Authors: Aron B Fisher
    Abstract:

    : Peroxiredoxin 6 (Prdx6) is a Ca2+-independent intracellular phospholipase A2 (called aiPLA2) that is localized to cytosol, lysosomes, and lysosomal-related organelles. Activity is minimal at cytosolic pH but is increased significantly with enzyme phosphorylation, at acidic pH, and in the presence of oxidized phospholipid substrate; maximal activity with phosphorylated aiPLA2 is ∼2 µmol/min/mg protein. Prdx6 is a "moonlighting" protein that also expresses glutathione peroxidase and lysophosphatidylcholine acyl transferase activities. The catalytic site for aiPLA2 activity is an S32-H26-D140 triad; S32-H26 is also the phospholipid binding site. Activity is inhibited by a serine "protease" inhibitor (diethyl p-nitrophenyl phosphate), an analog of the PLA2 transition state [1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol (MJ33)], and by two naturally occurring proteins (surfactant protein A and p67phox), but not by bromoenol lactone. aiPLA2 activity has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase type 2 (NOX2). The enzyme has been implicated in acute lung injury, carcinogenesis, neurodegenerative diseases, diabetes, male infertility, and sundry other conditions, although its specific roles have not been well defined. Protein mutations and animal models are now available to further investigate the roles of Prdx6-aiPLA2 activity in normal and pathological physiology.

  • Peroxiredoxin 6 phospholipid hydroperoxidase activity in the repair of peroxidized cell membranes
    Redox biology, 2018
    Co-Authors: Aron B Fisher, Elena M Sorokina, Chandra Dodia, Jose P Vasquezmedina, Sheldon I Feinstein
    Abstract:

    Abstract Although lipid peroxidation associated with oxidative stress can result in cellular death, sub-lethal lipid peroxidation can gradually resolve with return to the pre-exposure state. We have shown that resolution of lipid peroxidation is greatly delayed in lungs or cells that are null for Peroxiredoxin 6 (Prdx6) and that both the phospholipase A2 and the GSH peroxidase activities of Prdx6 are required for a maximal rate of recovery. Like other Peroxiredoxins, Prdx6 can reduce H2O2 and short chain hydroperoxides, but in addition can directly reduce phospholipid hydroperoxides. This study evaluated the relative role of these two different peroxidase activities of Prdx6 in the repair of peroxidized cell membranes. The His26 residue in Prdx6 is an important component of the binding site for phospholipids. Thus, we evaluated the lungs from H26A-Prdx6 expressing mice and generated H26A-Prdx6 expressing pulmonary microvascular endothelial cells (PMVEC) by lentiviral infection of Prdx6 null cells to compare with wild type in the repair of lipid peroxidation. Isolated lungs and PMVEC were exposed to tert-butyl hydroperoxide and mice were exposed to hyperoxia (> 95% O2). Assays for lipid peroxidation in wild type control and mutant lungs and cells showed ~4-fold increase at end-exposure. Control lungs and cells showed gradual resolution during a post-exposure recovery period. However, there was no recovery from lipid peroxidation by H26A-Prdx6 lungs or PMVEC. These studies confirm an important role for Prdx6 in recovery from membrane lipid peroxidation and indicate that reduction of H2O2 or short chain hydroperoxides does not play a role in the recovery process.

  • critical role of Peroxiredoxin 6 in the repair of peroxidized lung membrane phospholipids
    Free Radical Biology and Medicine, 2017
    Co-Authors: Aron B Fisher
    Abstract:

    Peroxidation of membrane lipids represents a severe threat to cellular integrity and its repair is crucial to prevent cell death. Peroxiredoxin 6 (Prdx6), a protein with both GSH peroxidase and phospholipase A2 (PLA2) activities, plays a major role in antioxidant defense of the lung, an organ with very low expression of GPx4.We investigated the role of Prdx6 in the repair of peroxidized cell membranes in intact mouse lungs and isolated pulmonary microvascular endothelial cells (PMVEC) treated with tert-butylhydroperoxide. Lipid peroxidation was evaluated by measurements of: a) thiobarbituric acid reactive substances (TBARS); b) oxidation of diphenyl-1-pyrenylphosphine (DPPP); and c) ferrous- xylenol orange (FOX). The exposure dose in the different models was varied to give a similar increase of about 4-fold over control in lipid peroxidation measurements at end-exposure. Values for lipid peroxidation returned to control levels within 2 h after oxidant removal in wild type (WT) lungs and PMVEC; however,there was essentially no repair in Pxdx6 null lungs or PMVEC. There also was no recovery in lungs and PMVEC that express H26A-Prdx6; this mutation abolishes the phospholipid hydroperoxidase function of Prdx6 but not its ability to reduce H2O2. An intermediate degree of repair was observed with lungs and PMVEC that express either C47S- or D140A-Prdx6; the former mutantion abolishes the peroxidase activity of Prdx6 while the latter abolishes PLA2 activity. Since repair was not seen with Prdx6 knock-out, GPx4 has no role in recovery from peroxidative stress by lung cells while Prdx6 plays a critical role; both the peroxidase and the PLA2 activities of Prdx6 contribute to the recovery process.

V I Novoselov - One of the best experts on this subject based on the ideXlab platform.

  • the effect of exogenous Peroxiredoxin 6 on the functional parameters of the isolated rat kidney
    Biophysics, 2020
    Co-Authors: A E Gordeeva, M G Sharapov, V I Novoselov, V A Evdokimov, E E Fesenko
    Abstract:

    Abstract—The aim of this study was to investigate the protective effect of exogenous Peroxiredoxins with ischemia–reperfusion of an isolated kidney. The study was carried out using a model of isolated rat kidney perfusion ex vivo. A recombinant Peroxiredoxin 6 was injected directly in the perfusion buffer. The high-molecular-weight dye Blue Dextran 2000 and urea were added to the perfusion buffer to determine the functionality of an isolated kidney. It was demonstrated that exogenous Peroxiredoxin 6 in the cortical layer of an isolated kidney was localized in the vessels of renal glomeruli; in the medulla it was found in microvessels surrounding the thin tubules. The use of Peroxiredoxin 6 decreases the degree of damage of nephron structures by two times compared with the damage in the control, which provides the preservation of ultrafiltration processes. A decrease in glomerular damage leads to a decrease in the content of Blue Dextran by two times compared with the damage in the control at the end of the perfusion period. A decrease in the damage of tubular structures indicates the active urea transport during perfusion. Thus, the inclusion of Peroxiredoxin 6 in the perfusion buffer mediated a decrease in the damage of nephron structures and maintenance of the multifunctional state of renal glomeruli and tubules.

  • Protective role of exogenous recombinant Peroxiredoxin 6 under ischemia-reperfusion injury of kidney
    Cell and Tissue Research, 2019
    Co-Authors: R G Goncharov, V I Novoselov, A A Temnov, K. A. Rogov, M G Sharapov
    Abstract:

    Peroxiredoxin 6 (Prx6) is an important antioxidant enzyme with various functions in the cell. Prx6 reduces a wide range of peroxide substrates, playing a leading role in maintaining the redox homeostasis of mammalian cells. In addition to the peroxidase activity, a phospholipase A2-like activity was demonstrated for Prx6, which plays an important role in the metabolism of membrane phospholipids. Besides that, due to its peroxidase and phospholipase activities, Prx6 participates in intracellular and intercellular signal transduction, thus triggering regenerative processes in the cell, suppressing apoptosis caused by various factors, including ischemia-reperfusion injuries. A nephroprotective effect of exogenous recombinant Prx6 administered before ischemia-reperfusion injury was demonstrated on an animal model. Exogenous Prx6 effectively alleviates the severeness of renal ischemia-reperfusion injuries and facilitates normalization of their structural and functional conditions. Infusion of exogenous Prx6 increases the survival rate of experimental animals by almost 3 times. Application of exogenous Prx6 can be an effective approach in the prevention and treatment of renal ischemia-reperfusion kidney lesions and in preserving isolated kidneys during transplantation.

  • radioprotective role of Peroxiredoxin 6
    Antioxidants, 2019
    Co-Authors: M G Sharapov, V I Novoselov, S V Gudkov
    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.

  • the effect of exogenous Peroxiredoxin 6 on the state of mesenteric vessels and the small intestine in ischemia reperfusion injury
    Biophysics, 2017
    Co-Authors: M G Sharapov, A E Gordeeva, E E Fesenko, V. K. Ravin, R G Goncharov, I V Tikhonova, A A Temnov, V I Novoselov
    Abstract:

    Oxidative stress is the main component of pathogenesis in ischemia–reperfusion injury. The administration of exogenous antioxidants suppresses oxidative stress and may decrease the severity of ischemia–reperfusion injury. The intestine is one of the most sensitive organs to the effect of ischemia–reperfusion. A rat model of a small intestine ischemia–reperfusion injury, based on occlusion of the superior mesenteric artery, was used in this work. Recombinant Peroxiredoxin 6, a representative of an ancient family of peroxidases that are able to neutralize a broad range of both organic and inorganic peroxides, was used as an exogenous antioxidant. The intravenous administration of the exogenous Peroxiredoxin 6 prior to ischemia–reperfusion minimizes tissue injury and reduces apoptotic cell death in the intestine and the mesenteric vessels. The impact of the exogenous Peroxiredoxin 6 upon the NO level elevation in animal blood has been shown to be correlated with the enhanced inducible NO synthase expression. Thus, the use of exogenous Peroxiredoxin 6 in ischemia–reperfusion injury of the intestine and the mesenteric vessels promotes normalization of the tissue redox homeostasis, structure protection, and restoration of the microvasculature.

  • The Effect of Exogenous Peroxiredoxin 6 on the State of Mesenteric Vessels and the Small Intestine in Ischemia–Reperfusion Injury
    Biophysics, 2017
    Co-Authors: M G Sharapov, A E Gordeeva, E E Fesenko, V. K. Ravin, R G Goncharov, I V Tikhonova, A A Temnov, V I Novoselov
    Abstract:

    Oxidative stress is the main component of pathogenesis in ischemia–reperfusion injury. The administration of exogenous antioxidants suppresses oxidative stress and may decrease the severity of ischemia–reperfusion injury. The intestine is one of the most sensitive organs to the effect of ischemia–reperfusion. A rat model of a small intestine ischemia–reperfusion injury, based on occlusion of the superior mesenteric artery, was used in this work. Recombinant Peroxiredoxin 6, a representative of an ancient family of peroxidases that are able to neutralize a broad range of both organic and inorganic peroxides, was used as an exogenous antioxidant. The intravenous administration of the exogenous Peroxiredoxin 6 prior to ischemia–reperfusion minimizes tissue injury and reduces apoptotic cell death in the intestine and the mesenteric vessels. The impact of the exogenous Peroxiredoxin 6 upon the NO level elevation in animal blood has been shown to be correlated with the enhanced inducible NO synthase expression. Thus, the use of exogenous Peroxiredoxin 6 in ischemia–reperfusion injury of the intestine and the mesenteric vessels promotes normalization of the tissue redox homeostasis, structure protection, and restoration of the microvasculature.

Sheldon I Feinstein - One of the best experts on this subject based on the ideXlab platform.

  • genetic inactivation of the phospholipase a2 activity of Peroxiredoxin 6 in mice protects against lps induced acute lung injury
    American Journal of Physiology-lung Cellular and Molecular Physiology, 2019
    Co-Authors: Sheldon I Feinstein, Elena M Sorokina, Jose Pablo Vazquezmedina, Priyal Patel, Renata Bannitzfernandes, Chandra Dodia, Shampa Chatterjee, Aron B Fisher
    Abstract:

    Peroxiredoxin 6 (Prdx6) is a multifunctional enzyme that serves important antioxidant roles by scavenging hydroperoxides and reducing peroxidized cell membranes. Prdx6 also plays a key role in cell...

  • mouse models of genetically altered Peroxiredoxin 6
    Antioxidants, 2019
    Co-Authors: Sheldon I Feinstein
    Abstract:

    Peroxiredoxin 6 (Prdx6) has been shown to have three enzymatic activities: peroxidase, phospholipase A2 (PLA2) and acyl transferase. The peroxidase activity is unusual, as it is capable of reducing phospholipid hydroperoxides (as well as hydrogen peroxide and short chain organic peroxides). Knockout and overexpressing mice have been produced that demonstrate the effect that eliminating or overproducing Prdx6 has on the animals’ physiology. In addition, mutations in various amino acids of Prdx6 have been identified that interfere with different enzymatic functions as well as protein transport. These mutations were originally characterized biochemically; subsequently, several knock-in mouse strains have been produced, each containing one mutation. These mice include the S32T knock-in that affects protein transport, the C47S knock-in that inactivates the peroxidase enzymatic activity, the D140A knock-in that inactivates the PLA2 enzymatic activity and the H26A knock-in that inactivates the peroxidase and blocks binding to phospholipids. This review summarizes the properties of these mice based upon studies conducted with the knockout, overexpressing and knock-in mice and the effect of the genetic changes on the biochemistry and physiology of these mice. The availability of these mice is also briefly discussed.

  • Peroxiredoxin 6 phospholipid hydroperoxidase activity in the repair of peroxidized cell membranes
    Redox biology, 2018
    Co-Authors: Aron B Fisher, Elena M Sorokina, Chandra Dodia, Jose P Vasquezmedina, Sheldon I Feinstein
    Abstract:

    Abstract Although lipid peroxidation associated with oxidative stress can result in cellular death, sub-lethal lipid peroxidation can gradually resolve with return to the pre-exposure state. We have shown that resolution of lipid peroxidation is greatly delayed in lungs or cells that are null for Peroxiredoxin 6 (Prdx6) and that both the phospholipase A2 and the GSH peroxidase activities of Prdx6 are required for a maximal rate of recovery. Like other Peroxiredoxins, Prdx6 can reduce H2O2 and short chain hydroperoxides, but in addition can directly reduce phospholipid hydroperoxides. This study evaluated the relative role of these two different peroxidase activities of Prdx6 in the repair of peroxidized cell membranes. The His26 residue in Prdx6 is an important component of the binding site for phospholipids. Thus, we evaluated the lungs from H26A-Prdx6 expressing mice and generated H26A-Prdx6 expressing pulmonary microvascular endothelial cells (PMVEC) by lentiviral infection of Prdx6 null cells to compare with wild type in the repair of lipid peroxidation. Isolated lungs and PMVEC were exposed to tert-butyl hydroperoxide and mice were exposed to hyperoxia (> 95% O2). Assays for lipid peroxidation in wild type control and mutant lungs and cells showed ~4-fold increase at end-exposure. Control lungs and cells showed gradual resolution during a post-exposure recovery period. However, there was no recovery from lipid peroxidation by H26A-Prdx6 lungs or PMVEC. These studies confirm an important role for Prdx6 in recovery from membrane lipid peroxidation and indicate that reduction of H2O2 or short chain hydroperoxides does not play a role in the recovery process.

  • the phospholipase a2 activity of Peroxiredoxin 6 modulates nadph oxidase 2 activation via lysophosphatidic acid receptor signaling in the pulmonary endothelium and alveolar macrophages
    The FASEB Journal, 2016
    Co-Authors: Jose Pablo Vazquezmedina, Sheldon I Feinstein, Chandra Dodia, Shampa Chatterjee, Liwei Weng, Clementina Mesaros, Ian A Blair, Aron B Fisher
    Abstract:

    Peroxiredoxin 6 (Prdx6) is essential for activation of NADPH oxidase type 2 (NOX2) in pulmonary microvascular endothelial cells (PMVECs), alveolar macrophages (AMs), and polymorphonuclear leukocyte...

  • binding sites for interaction of Peroxiredoxin 6 with surfactant protein a
    Biochimica et Biophysica Acta, 2016
    Co-Authors: Saikumari Y Krishnaiah, Sheldon I Feinstein, Elena M Sorokina, Chandra Dodia, Haitao Li, Aron B Fisher
    Abstract:

    Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase and phospholipase A2 (PLA2) activities. This protein participates in the degradation and remodeling of internalized dipalmitoylphosphatidylcholine (DPPC), the major phospholipid component of lung surfactant. We have shown previously that the PLA2 activity of Prdx6 is inhibited by the lung surfactant-associated protein called surfactant protein A (SP-A) through direct protein-protein interaction. Docking of SPA and Prdx6 was modeled using the ZDOCK (zlab.bu.edu) program in order to predict molecular sites for binding of the two proteins. The predicted peptide sequences were evaluated for binding to the opposite protein using isothermal titration calorimetry and circular dichroism measurement followed by determination of the effect of the SP-A peptide on the PLA2 activity of Prdx6. The sequences 195EEEAKKLFPK204.in the Prdx6 helix and 83DEELQTELYEIKHQIL99 in SP-A were identified as the sites for hydrophobic interaction and H+-bonding between the 2 proteins. Treatment of mouse endothelial cells with the SP-A peptide inhibited their recovery from lipid peroxidation associated with oxidative stress indicating inhibition of Prdx6 activity by the peptide in the intact cell.

M G Sharapov - One of the best experts on this subject based on the ideXlab platform.

  • the effect of exogenous Peroxiredoxin 6 on the functional parameters of the isolated rat kidney
    Biophysics, 2020
    Co-Authors: A E Gordeeva, M G Sharapov, V I Novoselov, V A Evdokimov, E E Fesenko
    Abstract:

    Abstract—The aim of this study was to investigate the protective effect of exogenous Peroxiredoxins with ischemia–reperfusion of an isolated kidney. The study was carried out using a model of isolated rat kidney perfusion ex vivo. A recombinant Peroxiredoxin 6 was injected directly in the perfusion buffer. The high-molecular-weight dye Blue Dextran 2000 and urea were added to the perfusion buffer to determine the functionality of an isolated kidney. It was demonstrated that exogenous Peroxiredoxin 6 in the cortical layer of an isolated kidney was localized in the vessels of renal glomeruli; in the medulla it was found in microvessels surrounding the thin tubules. The use of Peroxiredoxin 6 decreases the degree of damage of nephron structures by two times compared with the damage in the control, which provides the preservation of ultrafiltration processes. A decrease in glomerular damage leads to a decrease in the content of Blue Dextran by two times compared with the damage in the control at the end of the perfusion period. A decrease in the damage of tubular structures indicates the active urea transport during perfusion. Thus, the inclusion of Peroxiredoxin 6 in the perfusion buffer mediated a decrease in the damage of nephron structures and maintenance of the multifunctional state of renal glomeruli and tubules.

  • Protective role of exogenous recombinant Peroxiredoxin 6 under ischemia-reperfusion injury of kidney
    Cell and Tissue Research, 2019
    Co-Authors: R G Goncharov, V I Novoselov, A A Temnov, K. A. Rogov, M G Sharapov
    Abstract:

    Peroxiredoxin 6 (Prx6) is an important antioxidant enzyme with various functions in the cell. Prx6 reduces a wide range of peroxide substrates, playing a leading role in maintaining the redox homeostasis of mammalian cells. In addition to the peroxidase activity, a phospholipase A2-like activity was demonstrated for Prx6, which plays an important role in the metabolism of membrane phospholipids. Besides that, due to its peroxidase and phospholipase activities, Prx6 participates in intracellular and intercellular signal transduction, thus triggering regenerative processes in the cell, suppressing apoptosis caused by various factors, including ischemia-reperfusion injuries. A nephroprotective effect of exogenous recombinant Prx6 administered before ischemia-reperfusion injury was demonstrated on an animal model. Exogenous Prx6 effectively alleviates the severeness of renal ischemia-reperfusion injuries and facilitates normalization of their structural and functional conditions. Infusion of exogenous Prx6 increases the survival rate of experimental animals by almost 3 times. Application of exogenous Prx6 can be an effective approach in the prevention and treatment of renal ischemia-reperfusion kidney lesions and in preserving isolated kidneys during transplantation.

  • radioprotective role of Peroxiredoxin 6
    Antioxidants, 2019
    Co-Authors: M G Sharapov, V I Novoselov, S V Gudkov
    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.

  • the effect of exogenous Peroxiredoxin 6 on the state of mesenteric vessels and the small intestine in ischemia reperfusion injury
    Biophysics, 2017
    Co-Authors: M G Sharapov, A E Gordeeva, E E Fesenko, V. K. Ravin, R G Goncharov, I V Tikhonova, A A Temnov, V I Novoselov
    Abstract:

    Oxidative stress is the main component of pathogenesis in ischemia–reperfusion injury. The administration of exogenous antioxidants suppresses oxidative stress and may decrease the severity of ischemia–reperfusion injury. The intestine is one of the most sensitive organs to the effect of ischemia–reperfusion. A rat model of a small intestine ischemia–reperfusion injury, based on occlusion of the superior mesenteric artery, was used in this work. Recombinant Peroxiredoxin 6, a representative of an ancient family of peroxidases that are able to neutralize a broad range of both organic and inorganic peroxides, was used as an exogenous antioxidant. The intravenous administration of the exogenous Peroxiredoxin 6 prior to ischemia–reperfusion minimizes tissue injury and reduces apoptotic cell death in the intestine and the mesenteric vessels. The impact of the exogenous Peroxiredoxin 6 upon the NO level elevation in animal blood has been shown to be correlated with the enhanced inducible NO synthase expression. Thus, the use of exogenous Peroxiredoxin 6 in ischemia–reperfusion injury of the intestine and the mesenteric vessels promotes normalization of the tissue redox homeostasis, structure protection, and restoration of the microvasculature.

  • The Effect of Exogenous Peroxiredoxin 6 on the State of Mesenteric Vessels and the Small Intestine in Ischemia–Reperfusion Injury
    Biophysics, 2017
    Co-Authors: M G Sharapov, A E Gordeeva, E E Fesenko, V. K. Ravin, R G Goncharov, I V Tikhonova, A A Temnov, V I Novoselov
    Abstract:

    Oxidative stress is the main component of pathogenesis in ischemia–reperfusion injury. The administration of exogenous antioxidants suppresses oxidative stress and may decrease the severity of ischemia–reperfusion injury. The intestine is one of the most sensitive organs to the effect of ischemia–reperfusion. A rat model of a small intestine ischemia–reperfusion injury, based on occlusion of the superior mesenteric artery, was used in this work. Recombinant Peroxiredoxin 6, a representative of an ancient family of peroxidases that are able to neutralize a broad range of both organic and inorganic peroxides, was used as an exogenous antioxidant. The intravenous administration of the exogenous Peroxiredoxin 6 prior to ischemia–reperfusion minimizes tissue injury and reduces apoptotic cell death in the intestine and the mesenteric vessels. The impact of the exogenous Peroxiredoxin 6 upon the NO level elevation in animal blood has been shown to be correlated with the enhanced inducible NO synthase expression. Thus, the use of exogenous Peroxiredoxin 6 in ischemia–reperfusion injury of the intestine and the mesenteric vessels promotes normalization of the tissue redox homeostasis, structure protection, and restoration of the microvasculature.

A E Gordeeva - One of the best experts on this subject based on the ideXlab platform.

  • the effect of exogenous Peroxiredoxin 6 on the functional parameters of the isolated rat kidney
    Biophysics, 2020
    Co-Authors: A E Gordeeva, M G Sharapov, V I Novoselov, V A Evdokimov, E E Fesenko
    Abstract:

    Abstract—The aim of this study was to investigate the protective effect of exogenous Peroxiredoxins with ischemia–reperfusion of an isolated kidney. The study was carried out using a model of isolated rat kidney perfusion ex vivo. A recombinant Peroxiredoxin 6 was injected directly in the perfusion buffer. The high-molecular-weight dye Blue Dextran 2000 and urea were added to the perfusion buffer to determine the functionality of an isolated kidney. It was demonstrated that exogenous Peroxiredoxin 6 in the cortical layer of an isolated kidney was localized in the vessels of renal glomeruli; in the medulla it was found in microvessels surrounding the thin tubules. The use of Peroxiredoxin 6 decreases the degree of damage of nephron structures by two times compared with the damage in the control, which provides the preservation of ultrafiltration processes. A decrease in glomerular damage leads to a decrease in the content of Blue Dextran by two times compared with the damage in the control at the end of the perfusion period. A decrease in the damage of tubular structures indicates the active urea transport during perfusion. Thus, the inclusion of Peroxiredoxin 6 in the perfusion buffer mediated a decrease in the damage of nephron structures and maintenance of the multifunctional state of renal glomeruli and tubules.

  • expression of caspase 3 and the cytokine level in experimental reperfusion syndrome upon treatment with Peroxiredoxin 6
    Biophysics, 2017
    Co-Authors: A V Kubyshkin, A E Gordeeva, S V Novosyolov, I I Fomochkina, V Z Kharchenko, A A Pisarev, A A Beketov, A V Kochkina, M I Fedosov, L V Anisimova
    Abstract:

    Ischemia-reperfusion injury is a significant problem; there is a need for interpretation of its pathogenetic mechanism and a search for potential methods of correction. The aim of this study was to investigate the cytokine content and the proapoptotic protein expression, including caspase-3, in experimental ischemia–reperfusion injury, and to assess the effectiveness of Peroxiredoxin 6 treatment. Studies were conducted on 56 white male Wistar line rats weighing 180–200 g, in which ischemia–reperfusion injury was simulated by cross clamping both hind limbs. Proinflammatory cytokines in blood serum, the expression of caspase-3 in the cells of blood vessels, lungs, and kidneys were analyzed after ischemia–reperfusion injury and upon the Peroxiredoxin 6 preventive treatment. It was found that the progression of ischemia–reperfusion injury is followed by proinflammatory cytokine activation in the rat blood: the maximum values of interleukin 1β, which were almost 10 times higher than the control, have been observed by 12 h of reperfusion. Ischemia–reperfusion injury was accompanied by an caspase-3 increase in the cells of rat limb vessels and the lungs after 6 h of reperfusion. Peroxiredoxin 6 treatment neutralizes oxidative stress primarily in the limb blood vessels, reducing the degree of vessel tissue destruction in the hind limbs that should be considered as a target for therapy of ischemia–reperfusion injury.

  • the effect of exogenous Peroxiredoxin 6 on the state of mesenteric vessels and the small intestine in ischemia reperfusion injury
    Biophysics, 2017
    Co-Authors: M G Sharapov, A E Gordeeva, E E Fesenko, V. K. Ravin, R G Goncharov, I V Tikhonova, A A Temnov, V I Novoselov
    Abstract:

    Oxidative stress is the main component of pathogenesis in ischemia–reperfusion injury. The administration of exogenous antioxidants suppresses oxidative stress and may decrease the severity of ischemia–reperfusion injury. The intestine is one of the most sensitive organs to the effect of ischemia–reperfusion. A rat model of a small intestine ischemia–reperfusion injury, based on occlusion of the superior mesenteric artery, was used in this work. Recombinant Peroxiredoxin 6, a representative of an ancient family of peroxidases that are able to neutralize a broad range of both organic and inorganic peroxides, was used as an exogenous antioxidant. The intravenous administration of the exogenous Peroxiredoxin 6 prior to ischemia–reperfusion minimizes tissue injury and reduces apoptotic cell death in the intestine and the mesenteric vessels. The impact of the exogenous Peroxiredoxin 6 upon the NO level elevation in animal blood has been shown to be correlated with the enhanced inducible NO synthase expression. Thus, the use of exogenous Peroxiredoxin 6 in ischemia–reperfusion injury of the intestine and the mesenteric vessels promotes normalization of the tissue redox homeostasis, structure protection, and restoration of the microvasculature.

  • The Effect of Exogenous Peroxiredoxin 6 on the State of Mesenteric Vessels and the Small Intestine in Ischemia–Reperfusion Injury
    Biophysics, 2017
    Co-Authors: M G Sharapov, A E Gordeeva, E E Fesenko, V. K. Ravin, R G Goncharov, I V Tikhonova, A A Temnov, V I Novoselov
    Abstract:

    Oxidative stress is the main component of pathogenesis in ischemia–reperfusion injury. The administration of exogenous antioxidants suppresses oxidative stress and may decrease the severity of ischemia–reperfusion injury. The intestine is one of the most sensitive organs to the effect of ischemia–reperfusion. A rat model of a small intestine ischemia–reperfusion injury, based on occlusion of the superior mesenteric artery, was used in this work. Recombinant Peroxiredoxin 6, a representative of an ancient family of peroxidases that are able to neutralize a broad range of both organic and inorganic peroxides, was used as an exogenous antioxidant. The intravenous administration of the exogenous Peroxiredoxin 6 prior to ischemia–reperfusion minimizes tissue injury and reduces apoptotic cell death in the intestine and the mesenteric vessels. The impact of the exogenous Peroxiredoxin 6 upon the NO level elevation in animal blood has been shown to be correlated with the enhanced inducible NO synthase expression. Thus, the use of exogenous Peroxiredoxin 6 in ischemia–reperfusion injury of the intestine and the mesenteric vessels promotes normalization of the tissue redox homeostasis, structure protection, and restoration of the microvasculature.

  • Peroxiredoxin 6 is a natural radioprotector
    Doklady Biochemistry and Biophysics, 2016
    Co-Authors: M G Sharapov, S V Gudkov, A E Gordeeva, O E Karp, V E Ivanov, O V Shelkovskaya, V I Bruskov, V I Novoselov, E E Fesenko
    Abstract:

    After injection of 20 mg/kg Peroxiredoxin 6 to male Kv:SHK mice 15 min before X-ray irradiation in the range of lethal doses (7–10 Gy), the mice remained alive for 30 days, whereas the mortality of the control animals was 100%. In the irradiated animals, Peroxiredoxin 6 decreased the severity of radiation-induced leucopenia, granulocytopenia, and thrombocytopenia, increased the number of blood corpuscles, and prevented the mass death of epithelial cells and the destruction of the small intestine. Thus, Peroxiredoxin 6 can be regarded as a prophylactic radioprotective agent.