Peroxiredoxins in the Lung with Emphasis on Peroxiredoxin VI

  • Bruno Schremmer
  • Yefim Manevich
  • Sheldon I. Feinstein
  • Aron B. Fisher
Part of the Subcellular Biochemistry book series (SCBI, volume 44)


All six mammalian peroxiredoxins are expressed in the lung. Peroxiredoxin (Prx) VI is the isoform expressed at the highest level and its lung expression exceeds that for other organs. The predominant location of Prx VI is the cytosol and acidic organelles of Clara cells of the conducting airways and type II epithelial cells and macrophages in the alveoli. Prx I and VI show developmental induction of transcription at birth. PrxVI shares structural homology with other peroxiredoxins exhibiting a thioredoxin fold and a conserved catalytic Cys residue in the N-terminus of the protein. This enzyme is highly inducible by oxidative stress in both the neonatal and adult lung consistent with a role in antioxidant defense. Prx VI has several properties that distinguish its peroxidase activity from other peroxiredoxins: it can reduce phospholipid hydroperoxides in addition to other organic hydroperoxides and H2O2; the electron donor that serves to reduce the oxidized peroxidatic cysteine is not thioredoxin but GSH; instead of homodimerization, heterodimerization with pi-glutathione S-transferase is required for regeneration of the active enzyme. Prx VI also expresses a phospholipase A2 activity that is Ca2+-independent, maximal at acidic pH, and dependent on a serine-based catalytic triad and nucleophilic elbow at the surface of the protein. Models of altered Prx VI expression at the cellular, organ and whole animal levels have demonstrated that Prx VI functions as an important anti-oxidant enzyme with levels of protection that exceed those ascribed to GSH peroxidase (GPx1). The phospholipase A2 activity plays an important role in lung surfactant homeostasis and is responsible for the bulk of the degradation of internalized phosphatidylcholine and its resynthesis by the reacylation pathway. Expression of peroxiredoxins is elevated in several lung diseases including lung cancer, mesothelioma and sarcoidosis, although the mechanism for these alterations is not known. The unique properties of Prx VI enable it to play an important role in lung cell function


Gluathione peroxidase Glutathione S-transferase Phospholipase A2 Anti-oxidant defense Surfactant metabolism 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Akiba, S., Dodia, C., Chen, X., Fisher, A.B., 1998, Characterization of acidic Ca(2+)-independent phospholipase A2 of bovine lung. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 120: 393–404.PubMedCrossRefGoogle Scholar
  2. Antunes, F., Han, D., Cadenas, E., 2002, Relative contributions of heart mitochondria glutathione peroxidase and catalase to H(2)O(2) detoxification in vivo conditions. Free Radic. Biol. Med. 33: 1260–1267.PubMedCrossRefGoogle Scholar
  3. Arbibe, L., Koumanov, K., Vial, D., Rougeot, C., Faure, G., Havet, N., Longacre, S., Vargaftig, B.B., Bereziat, G., Voelker, D.R., Wolf, C., Touqui, L., 1998, Generation of lyso-phospholipids from surfactant in acute lung injury is mediated by type-II phospholipase A2 and inhibited by a direct surfactant protein A-phospholipase A2 protein interaction. J. Clin. Invest. 102: 1152–1160.PubMedCrossRefGoogle Scholar
  4. Batenburg, J J., Haagsman, H.P., 1998, The lipids of pulmonary surfactant: dynamics and interactions with proteins. Prog. Lipid Res. 37: 235–276.PubMedCrossRefGoogle Scholar
  5. Baughman, R.P., Lower, E.E., du Bois, R.M., 2003, Sarcoidosis. Lancet 361: 1111–1118.PubMedCrossRefGoogle Scholar
  6. Bouhafs, R.K., Jarstrand, C., 1999, Lipid peroxidation of lung surfactant by bacteria. Lung 177: 101–110.PubMedCrossRefGoogle Scholar
  7. Bouhafs, R.K., Samuelson, A., Jarstrand, C., 2003, Lipid peroxidation of lung surfactant due to reactive oxygen species released from phagocytes stimulated by bacteria from children with cystic fibrosis. Free Radic. Res. 37: 909–917.PubMedCrossRefGoogle Scholar
  8. Brenner, S., 1988, The molecular evolution of genes and proteins: a tale of two serines. Nature 334: 528–530. PubMedCrossRefGoogle Scholar
  9. Chae, H.Z., Kim, H.J., Kang, S.W., Rhee, S.G., 1999, Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin. Diabetes Res. Clin. Pract. 45: 101–112. PubMedCrossRefGoogle Scholar
  10. Chang, J.W., Jeon, H.B., Lee, J.H., Yoo, J.S., Chun, J.S., Kim, J.H., Yoo, Y.J., 2001, Augmented expression of peroxiredoxin I in lung cancer. Biochem. Biophys. Res. Commun. 289: 507–512.PubMedCrossRefGoogle Scholar
  11. Chang, J.W., Lee, S.H., Jeong, J.Y., Chae, H.Z., Kim, Y.C., Park, Z.Y., Yoo, Y.J., 2005, Peroxiredoxin-I is an autoimmunogenic tumor antigen in non-small cell lung cancer. FEBS Lett. 579: 2873–2877.PubMedCrossRefGoogle Scholar
  12. Chang, T.S., Jeong, W., Woo, H.A., Lee, S.M., Park, S., Rhee, S.G., 2004, Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine. J. Biol. Chem. 279: 50994–51001.PubMedCrossRefGoogle Scholar
  13. Chen, JW., Dodia, C., Feinstein, S.I., Jain, M.K., Fisher, A.B., 2000, 1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities. J. Biol. Chem. 275: 28421–28427.PubMedCrossRefGoogle Scholar
  14. Chen, M.F., Keng, P.C., Shau, H., Wu, C.T., Hu, Y.C., Liao, S.K., Chen, W.C., 2006, Inhibition of lung tumor growth and augmentation of radiosensitivity by decreasing peroxiredoxin I expression. Int. J. Radiat. Oncol. Biol. Phys. 64: 581–591.PubMedGoogle Scholar
  15. Choi, H.J., Kang, S.W., Yang, C.H., Rhee, S.G., Ryu, S.E., 1998, Crystal structure of a novel human peroxidase enzyme at 2.0 A resolution. Nat. Struct. Biol. 5: 400–406.PubMedCrossRefGoogle Scholar
  16. Das, K.C., Pahl, P.M., Guo, X.L., White, C.W., 2001, Induction of peroxiredoxin gene expression by oxygen in lungs of newborn primates. Am. J. Respir. Cell. Mol. Biol. 25: 226–232.PubMedGoogle Scholar
  17. Declercq, J.P., Evrard, C., Clippe, A., Stricht, D.V., Bernard, A., Knoops, B., 2001, Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 A resolution. J. Mol. Biol. 311: 751–759.PubMedCrossRefGoogle Scholar
  18. Dierick, J.F., Wenders, F., Chainiaux, F., Remacle, J., Fisher, A.B., Toussaint, O., 2003, Retrovirally mediated overexpression of peroxiredoxin VI increases the survival of WI-38 human diploid fibroblasts exposed to cytotoxic doses of tert-butylhydroperoxide and UVB. Biogerontology 4: 125–131.PubMedCrossRefGoogle Scholar
  19. Ding, L., Liu, Z., Zhu, Z., Luo, G., Zhao, D., Ni, J., 1998, Biochemical characterization of selenium-containing catalytic antibody as a cytosolic glutathione peroxidase mimic. Biochem. J. 332 (Pt 1): 251–255.PubMedGoogle Scholar
  20. Evrard, C., Capron, A., Marchand, C., Clippe, A., Wattiez, R., Soumillion, P., Knoops, B., Declercq, J.P., 2004, Crystal structure of a dimeric oxidized form of human peroxiredoxin 5. J. Mol. Biol. 337: 1079–1090.PubMedCrossRefGoogle Scholar
  21. Fisher, A.B., Al-Mehdi, A.B., Muzykantov, V., 1999a, Activation of endothelial NADPH oxidase as the source of a reactive oxygen species in lung ischemia. Chest 116: 25S-26S.CrossRefGoogle Scholar
  22. Fisher, A.B., Dodia, C., 1996, Role of phospholipase A2 enzymes in degradation of dipalmitoylphosphatidylcholine by granular pneumocytes. J. Lipid Res. 37: 1057–1064.PubMedGoogle Scholar
  23. Fisher, A.B., Dodia, C., 1997, Role of acidic Ca2+-independent phospholipase A2 in synthesis of lung dipalmitoyl phosphatidylcholine. Am. J. Physiol. 272: L238–243.PubMedGoogle Scholar
  24. Fisher, A.B., Dodia, C., 2001, Lysosomal-type PLA2 and turnover of alveolar DPPC. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L748–754.PubMedGoogle Scholar
  25. Fisher, A.B., Dodia, C., Chander, A., 1994, Inhibition of lung calcium-independent phospholipase A2 by surfactant protein A. Am. J. Physiol. 267: L335–341.PubMedGoogle Scholar
  26. Fisher, A.B., Dodia, C., Feinstein, S.I., Ho, Y. S., 2005, Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A2. J. Lipid Res. 46: 1248–1256.PubMedCrossRefGoogle Scholar
  27. Fisher, A.B., Dodia, C., Manevich, Y., Chen, J.W., Feinstein, S.I., 1999b, Phospholipid hydroperoxides are substrates for non-selenium glutathione peroxidase. J. Biol. Chem. 274: 21326–21334.CrossRefGoogle Scholar
  28. Fisher, A.B., Dodia, C., Yu, K., Manevich, Y., Feinstein, S.I., 2006, Lung phospholipid metabolism in transgenic mice overexpressing peroxiredoxin 6. Biochim. Biophys. Acta 1761: 785–792.PubMedGoogle Scholar
  29. Flohè, L., Brigelius-Flohè, R., 2001, Selenoproteins of the glutathione system. in D. L. Hatfield: Selenium. Its Molecular Biology and Role in Human Health. London, Kluwer Academic Publishers, pp. 157–178.Google Scholar
  30. Fujii, T., Fujii, J. Taniguchi, N., 2001, Augmented expression of peroxiredoxin VI in rat lung and kidney after birth implies an antioxidative role. Eu.r J. Biochem. 268: 218–225.CrossRefGoogle Scholar
  31. Fukuhara, R., Kageyama, T., 2005, Structure, gene expression, and evolution of primate glutathione peroxidases. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 141: 428–436.PubMedCrossRefGoogle Scholar
  32. Gilliard, N., Heldt, G.P., Loredo, J., Gasser, H., Redl, H., Merritt, T.A., Spragg, R.G., 1994, Exposure of the hydrophobic components of porcine lung surfactant to oxidant stress alters surface tension properties. J. Clin. Invest. 93: 2608–2615.PubMedCrossRefGoogle Scholar
  33. Grossmann, A., Wendel, A., 1983, Non-reactivity of the selenoenzyme glutathione peroxidase with enzymatically hydroperoxidized phospholipids. Eur. J. Biochem. 135: 549–552.PubMedCrossRefGoogle Scholar
  34. Hirotsu, S., Abe, Y., Okada, K., Nagahara, N., Hori, H., Nishino, T., Hakoshima, T., 1999, Crystal structure of a multifunctional 2-Cys peroxiredoxin heme-binding protein 23 kDa/proliferation-associated gene product. Proc. Natl. Acad. Sci. U S A 96: 12333–12338.PubMedCrossRefGoogle Scholar
  35. Ho, Y.S., Magnenat, J.L., Bronson, R T., Cao, J., Gargano, M., Sugawara, M., Funk, C.D., 1997, Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J. Biol. Chem. 272: 16644–16651.PubMedCrossRefGoogle Scholar
  36. Hofmann, B., Hecht, H.J., Flohè, L., 2002, Peroxiredoxins. Biol. Chem. 383: 347–364.PubMedCrossRefGoogle Scholar
  37. Iakoubova, O.A., Pacella, L.A., Her, H., Beier, D.R., 1997, LTW4 protein on mouse chromosome 1 is a member of a family of antioxidant proteins. Genomics 42: 474–478.PubMedCrossRefGoogle Scholar
  38. Jain, D., Dodia, C., Bates, S.R., Hawgood, S., Poulain, F.R., Fisher, A.B., 2003, SP-A is necessary for increased clearance of alveolar DPPC with hyperventilation or secretagogues. Am. J. Physiol. Lung Cell. Mol. Physiol. 284: L759–765.PubMedGoogle Scholar
  39. Kang, S.W., Baines, I.C., Rhee, S.G., 1998, Characterization of a mammalian peroxiredoxin that contains one conserved cysteine. J. Biol. Chem. 273: 6303–6311.PubMedCrossRefGoogle Scholar
  40. Kim, H. S., Kang, S. W., Rhee, S. G., and Clerch, L. B., 2001, Rat lung peroxiredoxins I and II are differentially regulated during development and by hyperoxia. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L1212–1217.PubMedGoogle Scholar
  41. Kim, H.S., Manevich, Y., Feinstein, S.I., Pak, J.H., Ho, Y.S., Fisher, A.B., 2003, Induction of 1-cys peroxiredoxin expression by oxidative stress in lung epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 285: L363–369.PubMedGoogle Scholar
  42. Kim, H.S., Pak, J.H., Gonzales, L.W., Feinstein, S.I., Fisher, A.B., 2002, Regulation of 1-cys peroxiredoxin expression in lung epithelial cells. Am. J. Respir. Cell. Mol. Biol. 27: 227–233.PubMedGoogle Scholar
  43. Kim, T.S., Dodia, C., Chen, X., Hennigan, B.B., Jain, M., Feinstein, S.I., Fisher, A.B., 1998, Cloning and expression of rat lung acidic Ca(2+)-independent PLA2 and its organ distribution. Am. J. Physiol. 274: L750–761.PubMedGoogle Scholar
  44. Kim, T.S., Sundaresh, C.S., Feinstein, S.I., Dodia, C., Skach, W.R., Jain, M.K., Nagase, T., Seki, N., Ishikawa, K., Nomura, N., Fisher, A.B., 1997, Identification of a human cDNA clone for lysosomal type Ca2+-independent phospholipase A2 and properties of the expressed protein. J. Biol. Chem. 272: 2542–2550.PubMedCrossRefGoogle Scholar
  45. Kinnula, V.L., Lehtonen, S., Kaarteenaho-Wiik, R., Lakari, E., Paakko, P., Kang, S.W., Rhee, S.G., Soini, Y., 2002a, Cell specific expression of peroxiredoxins in human lung and pulmonary sarcoidosis. Thorax 57: 157–164.CrossRefGoogle Scholar
  46. Kinnula, V.L., Lehtonen, S., Sormunen, R., Kaarteenaho-Wiik, R., Kang, S. W., Rhee, S.G., Soini, Y., 2002b, Overexpression of peroxiredoxins I, II, III, V, and VI in malignant mesothelioma. J. Pathol. 196: 316–323.CrossRefGoogle Scholar
  47. Kinnula, V.L., Paakko, P., Soini, Y., 2004, Antioxidant enzymes and redox regulating thiol proteins in malignancies of human lung. FEBS Lett. 569: 1–6.PubMedCrossRefGoogle Scholar
  48. Knoops, B., Clippe, A., Bogard, C., Arsalane, K., Wattiez, R., Hermans, C., Duconseille, E., Falmagne, P., Bernard, A., 1999, Cloning and characterization of AOEB166, a novel mammalian antioxidant enzyme of the peroxiredoxin family. J. Biol.Chem. 274: 30451–30458.PubMedCrossRefGoogle Scholar
  49. Koura, T., Gon, Y., Hashimoto, S., Azuma, A., Kudoh, S., Fukuda, Y., Sugawara, I., Yodoi, J., Horie, T., 2000, Expression of thioredoxin in granulomas of sarcoidosis: possible role in the development of T lymphocyte activation. Thorax 55: 755–761.PubMedCrossRefGoogle Scholar
  50. Kuzmenko, A.I., Wu, H., Bridges, J.P., McCormack, F.X., 2004, Surfactant lipid peroxidation damages surfactant protein A and inhibits interactions with phospholipid vesicles. J. Lipid Res. 45: 1061–1068.PubMedCrossRefGoogle Scholar
  51. Lakari, E., Paakko, P., Kinnula, V.L., 1998, Manganese superoxide dismutase, but not CuZn superoxide dismutase, is highly expressed in the granulomas of pulmonary sarcoidosis and extrinsic allergic alveolitis. Am. J. Respi.r Crit. Care Med. 158: 589–596.Google Scholar
  52. Leavey, P.J., Gonzalez-Aller, C., Thurman, G., Kleinberg, M., Rinckel, L., Ambruso, D. W., Freeman, S., Kuypers, F.A., Ambruso, D.R., 2002, A 29-kDa protein associated with p67phox expresses both peroxiredoxin and phospholipase A2 activity and enhances superoxide anion production by a cell-free system of NADPH oxidase activity. J. Biol. Chem. 277: 45181–45187.PubMedCrossRefGoogle Scholar
  53. Lee, J.H., Daud, A.N., Cribbs, L.L., Lacerda, A.E., Pereverzev, A., Klockner, U., Schneider, T., Perez-Reyes, E., 1999, Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family. J. Neurosci. 19: 1912–1921.PubMedGoogle Scholar
  54. Lee, S.P., Hwang, Y.S., Kim, Y.J., Kwon, K.S., Kim, H.J., Kim, K., Chae, H.Z., 2001, Cyclophilin a binds to peroxiredoxins and activates its peroxidase activity. J. Biol. Chem. 276: 29826–29832.PubMedCrossRefGoogle Scholar
  55. Lee, T.H., Kim, S.J., Kang, S.W., Lee, K.K., Rhee, S.G., Yu, D.Y., 2000, Molecular cloning and characterization of the mouse peroxiredoxin V gene. Biochem. Biophys. Res. Commun. 270: 356–362.PubMedCrossRefGoogle Scholar
  56. Lehtonen, S.T., Svensk, A.M., Soini, Y., Paakko, P., Hirvikoski, P., Kang, S.W., Saily, M., Kinnula, V.L., 2004, Peroxiredoxins, a novel protein family in lung cancer. Int. J. Cancer 111: 514–521.PubMedCrossRefGoogle Scholar
  57. Leyens, G., Donnay, I., Knoops, B., 2003, Cloning of bovine peroxiredoxins-gene expression in bovine tissues and amino acid sequence comparison with rat, mouse and primate peroxiredoxins. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 136: 943–955.PubMedCrossRefGoogle Scholar
  58. Manevich, Y., Feinstein, S.I., Fisher, A.B., 2004, Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires glutathionylation mediated by heterodimerization with pi GST. Pro.c Natl. Acad. Sci. U S A 101: 3780–3785.CrossRefGoogle Scholar
  59. Manevich, Y., Fisher, A.B., 2005, Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism. Free Radic. Biol. Med. 38: 1422–1432.PubMedCrossRefGoogle Scholar
  60. Manevich, Y., Reddy, K. S., Shuvaeva, T., Feinstein, S.I., Fisher, A.B. (2005). Circular dichroism (CD) and fluorescence studies of phospholipids to peroxiredoxin 6 (Prdx 6). Faseb J..Google Scholar
  61. Manevich, Y., Sweitzer, T., Pak, J.H., Feinstein, S.I., Muzykantov, V., Fisher, A.B., 2002, 1-Cys peroxiredoxin overexpression protects cells against phospholipid peroxidation-mediated membrane damage. Proc. Natl. Acad. Sci.U S A 99: 11599–11604.PubMedCrossRefGoogle Scholar
  62. Matsumoto, A., Okado, A., Fujii, T., Fujii, J., Egashira, M., Niikawa, N., Taniguchi, N., 1999, Cloning of the peroxiredoxin gene family in rats and characterization of the fourth member. FEBS Lett. 443: 246–250.PubMedCrossRefGoogle Scholar
  63. Michiels, C., Raes, M., Toussaint, O., Remacle, J., 1994, Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic. Biol. Med. 17: 235–248.PubMedCrossRefGoogle Scholar
  64. Mo, Y., Feinstein, S. I., Manevich, Y., Zhang, Q., Lu, L., Ho, Y.S., Fisher, A.B., 2003, 1-Cys peroxiredoxin knock-out mice express mRNA but not protein for a highly related intronless gene. FEBS Lett. 555: 192–198.PubMedCrossRefGoogle Scholar
  65. Mossman, B.T., Churg, A., 1998, Mechanisms in the pathogenesis of asbestosis and silicosis. Am. J. Respir. Crit. Care Med. 157: 1666–1680.PubMedGoogle Scholar
  66. Munz, B., Frank, S., Hubner, G., Olsen, E., Werner, S., 1997, A novel type of glutathione peroxidase: expression and regulation during wound repair. Biochem. J. 326 (Pt 2): 579–585.PubMedGoogle Scholar
  67. Nagase, T., Miyajima, N., Tanaka, A., Sazuka, T., Seki, N., Sato, S., Tabata, S., Ishikawa, K., Kawarabayasi, Y., Kotani, H., et al., 1995, Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1 (supplement). DNA Res. 2: 51–59.PubMedCrossRefGoogle Scholar
  68. Nardini, M., Dijkstra, B.W., 1999, Alpha/beta hydrolase fold enzymes: the family keeps growing. Curr. Opin. Struct. Biol. 9: 732–737.PubMedCrossRefGoogle Scholar
  69. Noguera-Mazon, V., Lemoine, J., Walker, O., Rouhier, N., Salvador, A., Jacquot, J.P., Lancelin, J.M., Krimm, I., 2006, Glutathionylation induces the dissociation of 1-Cys D-peroxiredoxin non-covalent homodimer. J. Biol. Chem. 281: 31736–31742.PubMedCrossRefGoogle Scholar
  70. Ollis, D.L., Cheah, E., Cygler, M., Dijkstra, B., Frolow, F., Franken, S.M., Harel, M., Remington, S.J., Silman, I., Schrag, J., et al., 1992, The alpha/beta hydrolase fold. Protein Eng. 5: 197–211.PubMedCrossRefGoogle Scholar
  71. Pak, J.H., Manevich, Y., Kim, H.S., Feinstein, S.I., Fisher, A.B., 2002, An antisense oligonucleotide to 1-cys peroxiredoxin causes lipid peroxidation and apoptosis in lung epithelial cells. J. Biol. Chem. 277: 49927–49934.PubMedCrossRefGoogle Scholar
  72. Peshenko, I.V., Novoselov, V.I., Evdokimov, V.A., Nikolaev Y.V., Shuvaeva, T.M., Lipkin, V.M., Fesenko, E.E., 1996, Novel 28-kDa secretory protein from rat olfactory epithelium. FEBS Lett. 381: 12–14.PubMedCrossRefGoogle Scholar
  73. Peshenko, I.V., Novoselov, V.I., Evdokimov, V.A., Nikolaev, Y.V., Kamzalov, S.S., Shuvaeva, T.M., Lipkin, V.M., Fesenko, E.E., 1998, Identification of a 28 kDa secretory protein from rat olfactory epithelium as a thiol-specific antioxidant. Free Radic. Biol. Med. 25: 654–659.PubMedCrossRefGoogle Scholar
  74. Peshenko, I.V., Shichi, H., 2001, Oxidation of active center cysteine of bovine 1-Cys peroxiredoxin to the cysteine sulfenic acid form by peroxide and peroxynitrite. Free Radic. Biol. Med. 31: 292–303.PubMedCrossRefGoogle Scholar
  75. Peshenko, I.V., Singh, A.K., Shichi, H., 2001, Bovine eye 1-Cys peroxiredoxin: expression in E. coli and antioxidant properties. J. Ocul. Pharmacol. Ther. 17: 93–99.PubMedCrossRefGoogle Scholar
  76. Phelan, S.A., Beier, D.R., Higgins, D.C., Paigen, B., 2002, Confirmation and high resolution mapping of an atherosclerosis susceptibility gene in mice on Chromosome 1. Mamm. Genome 13: 548–553.PubMedCrossRefGoogle Scholar
  77. Phelan, S.A., Johnson, K.A., Beier, D.R., Paigen, B., 1998, Characterization of the murine gene encoding Aop2 (antioxidant protein 2) and identification of two highly related genes. Genomics 54: 132–139.PubMedCrossRefGoogle Scholar
  78. Pisani, R.J., Colby, T.V., Williams, D.E., 1988, Malignant mesothelioma of the pleura. Mayo Clin. Proc. 63: 1234–1244.PubMedGoogle Scholar
  79. Poole, L.B., Karplus, P.A., Claiborne, A., 2004, Protein sulfenic acids in redox signaling. Annu. Rev. Pharmacol. Toxicol. 44: 325–347.PubMedCrossRefGoogle Scholar
  80. Power, J.H., Nicholas, T.E., 1999, Immunohistochemical localization and characterization of a rat Clara cell 26-kDa protein (CC26) with similarities to glutathione peroxidase and phospholipase A2. Exp. Lung. Res. 25: 379–392.PubMedCrossRefGoogle Scholar
  81. Ralat, L.A., Manevich, Y., Fisher, A.B., Colman, R.F., 2006, Direct evidence for the formation of a complex between 1-cysteine peroxiredoxin and glutathione S-transferase pi with activity changes in both enzymes. Biochemistry 45: 360–372.PubMedCrossRefGoogle Scholar
  82. Rhee, S.G., Kang, S.W., Chang, T.S., Jeong, W., Kim, K., 2001, Peroxiredoxin, a novel family of peroxidases. IUBMB Life 52: 35–41.PubMedCrossRefGoogle Scholar
  83. Rhee, S.G., Kang, S.W., Jeong, W., Chang, T.S., Yang, K.S., Woo, H.A., 2005, Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins. Curr. Opin. Cell Biol. 17: 183–189.PubMedCrossRefGoogle Scholar
  84. Rhee, S.G., Kang, S.W., Netto, L.E., Seo, M.S., Stadtman, E.R., 1999, A family of novel peroxidases, peroxiredoxins. Biofactors 10: 207–209.PubMedCrossRefGoogle Scholar
  85. Sevanian, A., Muakkassah-Kelly, S.F., Montestruque, S., 1983, The influence of phospholipase A2 and glutathione peroxidase on the elimination of membrane lipid peroxides. Arch. Biochem. Biophys. 223: 441–452.PubMedCrossRefGoogle Scholar
  86. Shichi, H., 1990, Glutathione-dependent detoxification of peroxide in bovine ciliary body. Ex.p Eye Res. 50: 813–818.CrossRefGoogle Scholar
  87. Shichi, H., Demar, J.C., 1990, Non-selenium glutathione peroxidase without glutathione S-transferase activity from bovine ciliary body. Exp. Eye Res. 50: 513–520.PubMedCrossRefGoogle Scholar
  88. Simeone, M., Phelan, S.A., 2005, Transcripts associated with Prdx6 (peroxiredoxin 6) and related genes in mouse. Mamm. Genome 16: 103–111.PubMedCrossRefGoogle Scholar
  89. Sinning, I., Kleywegt, G. J., Cowan, S.W., Reinemer, P., Dirr, H.W., Huber, R., Gilliland, G.L., Armstrong, R.N., Ji, X., Board, P.G., et al., 1993, Structure determination and refinement of human alpha class glutathione transferase A1–1, and a comparison with the Mu and Pi class enzymes. J. Mol. Biol. 232: 192–212.PubMedCrossRefGoogle Scholar
  90. Six, D.A., Dennis, E.A., 2000, The expanding superfamily of phospholipase A(2) enzymes: classification and characterization. Biochim. Biophys. Acta 1488: 1–19.PubMedGoogle Scholar
  91. Sparling, N.E., Phelan, S.A., 2003, Identification of multiple transcripts for antioxidant protein 2 (Aop2): differential regulation by oxidative stress and growth factors. Redox Rep. 8: 87–94.PubMedCrossRefGoogle Scholar
  92. Stripp, B.R., Reynolds, S.D., Boe, I.M., Lund, J., Power, J.H., Coppens, J.T., Wong, C.M., Reynolds, P.R., Plopper, C.G., 2002, Clara cell secretory protein deficiency alters clara cell secretory apparatus and the protein composition of airway lining fluid. Am. J. Respir. Cell. Mol. Biol. 27: 170–178.PubMedGoogle Scholar
  93. Tolle, A., Schlame, M., Charlier, N., Guthmann, F., Rustow, B., 2005, Vitamin E differentially regulates the expression of peroxiredoxin-1 and -6 in alveolar type II cells. Free Radic. Biol. Med. 38: 1401–1408.PubMedCrossRefGoogle Scholar
  94. Ursini, F., Maiorino, M., Brigelius-Flohe, R., Aumann, K.D., Roveri, A., Schomburg, D., Flohe, L., 1995, Diversity of glutathione peroxidases. Methods Enzymol. 252: 38–53.PubMedCrossRefGoogle Scholar
  95. Wang, X., Phelan, S.A., Forsman-Semb, K., Taylor, E.F., Petros, C., Brown, A., Lerner, C.P., Paigen, B., 2003, Mice with targeted mutation of peroxiredoxin 6 develop normally but are susceptible to oxidative stress. J. Biol. Chem. 278: 25179–25190.PubMedCrossRefGoogle Scholar
  96. Wang, X., Phelan, S.A., Petros, C., Taylor, E.F., Ledinski, G., Jurgens, G., Forsman-Semb, K., Paigen, B., 2004a, Peroxiredoxin 6 deficiency and atherosclerosis susceptibility in mice: significance of genetic background for assessing atherosclerosis. Atherosclerosis 177: 61–70.CrossRefGoogle Scholar
  97. Wang, Y., Feinstein, S.I., Manevich, Y., Ho, Y.S., Fisher, A.B., 2004b, Lung injury and mortality with hyperoxia are increased in peroxiredoxin 6 gene-targeted mice. Free Radic. Biol. Med. 37: 1736–1743.CrossRefGoogle Scholar
  98. Wang, Y., Feinstein, S.I., Manevich, Y., Ho, Y.S., Fisher, A.B., 2006a, Peroxiredoxin 6 gene-targeted mice show increased lung injury with paraquat-induced oxidative stress. Antioxid. Redox Signal. 8: 229–237.CrossRefGoogle Scholar
  99. Wang, Y., Manevich, Y., Feinstein, S.I., Fisher, A.B., 2004c, Adenovirus-mediated transfer of the 1-cys peroxiredoxin gene to mouse lung protects against hyperoxic injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L1188–1193.CrossRefGoogle Scholar
  100. Wang, Y., Phelan, S.A., Manevich, Y., Feinstein, S.I., Fisher, A.B., 2006, Transgenic mice overexpressing peroxiredoxin 6 show increased resistance to lung injury in hyperoxia. Am. J. Respir. Cell Mol. Biol. 34: 481–486.PubMedCrossRefGoogle Scholar
  101. Wattiez, R., Hermans, C., Bernard, A., Lesur, O., Falmagne, P., 1999, Human bronchoalveolar lavage fluid: two-dimensional gel electrophoresis, amino acid microsequencing and identification of major proteins. Electrophoresis 20: 1634–1645.PubMedCrossRefGoogle Scholar
  102. Wattiez, R., Hermans, C., Cruyt, C., Bernard, A., Falmagne, P., 2000, Human bronchoalveolar lavage fluid protein two-dimensional database: study of interstitial lung diseases. Electrophoresis 21: 2703–2712.PubMedCrossRefGoogle Scholar
  103. Whitsett, J.A., Weaver, T.E., 2002, Hydrophobic surfactant proteins in lung function and disease. New Engl. J. Med. 347: 2141–2148.PubMedCrossRefGoogle Scholar
  104. Wood, Z.A., Schroder, E., Harris, J.R., Poole, L.B., 2003, Structure, mechanism and regulation of peroxiredoxins. Trends Biochem. Sci. 28: 32–40.PubMedCrossRefGoogle Scholar
  105. Wu, Y.Z., Manevich, Y., Baldwin, J.L., Dodia, C., Yu, K., Feinstein, S.I., Fisher, A.B., 2006, Interaction of surfactant protein A with peroxiredoxin 6 regulates phospholipase A2 activity. J. Biol. Chem. 281: 7515–7525.PubMedCrossRefGoogle Scholar
  106. Zhao, L., Wang, H.P., Zhang, H.J., Weydert, C.J., Domann, F.E., Oberley, L.W., Buettner, G.R., 2003, L-PhGPx expression can be suppressed by antisense oligodeoxynucleotides. Arch. Biochem. Biophys. 417: 212–218.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Bruno Schremmer
    • 1
  • Yefim Manevich
    • 1
  • Sheldon I. Feinstein
    • 1
  • Aron B. Fisher
    • 1
  1. 1.Institute for Environmental MedicineUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations