Peroxidases are enzymes that reduce hydroperoxide substrates. In many cases, hydroperoxide reduction is coupled to the formation of a disulfide bond, which is transferred onto specific acceptor molecules, the so-called reducing substrates. As such, peroxidases control the spatiotemporal distribution of diffusible second messengers such as hydrogen peroxide (H2O2) and generate new disulfides. Members of two families of peroxidases, peroxiredoxins (Prxs) and glutathione peroxidases (GPxs), reside in different subcellular compartments or are secreted from cells. This review discusses the properties and physiological roles of PrxIV, GPx7, and GPx8 in the endoplasmic reticulum (ER) of higher eukaryotic cells where H2O2 and—possibly—lipid hydroperoxides are regularly produced. Different peroxide sources and reducing substrates for ER peroxidases are critically evaluated. Peroxidase-catalyzed detoxification of hydroperoxides coupled to the productive use of disulfides, for instance, in the ER-associated process of oxidative protein folding, appears to emerge as a common theme. Nonetheless, in vitro and in vivo studies have demonstrated that individual peroxidases serve specific, nonoverlapping roles in ER physiology. 1. Introduction Hydrogen peroxide (H2O2) is an intracellular metabolite, which serves important roles as a second messenger in redox signaling [1]. However, since elevated levels of H2O2 (and of other reactive oxygen species, ROS) can damage proteins, nucleic acids, and lipids by peroxidation, temporal and spatial limitation of H2O2 levels is critically important. Thus, half-life and spatial distribution of H2O2 in the cell are tightly regulated by nonenzymatic antioxidants as well as by specific scavenging enzymes, including the so-called peroxidases of the peroxiredoxin (Prx) or glutathione peroxidase (GPx) families [2]. Prx and GPx isoforms reside in different subcellular compartments where they catalyze the reduction of H2O2 to H2O [2]. The most relevant producers of intracellular ROS/H2O2 are the transmembrane enzyme complexes of the nicotinamide adenine dinucleotide oxidase (NOX) family, various enzymes and the respiratory chain in mitochondria, peroxisomal enzymes, and sulfhydryl oxidases in the endoplasmic reticulum (ER) [3–7]. Due to the presence of specific aquaporin channels in cellular membranes, the local diffusion of H2O2 is usually not restricted by organelle boundaries [8, 9]. There are a total of six isoforms of Prx in mammals, all of which form distinct types of antiparallel homooligomers [10]. H2O2-mediated oxidation of the
References
[1]
A. Bindoli and M. P. Rigobello, “Principles in redox signaling: from chemistry to functional significance,” Antioxidants & Redox Signaling, vol. 18, no. 13, pp. 1557–1593, 2013.
[2]
L. Flohé, S. Toppo, G. Cozza, and F. Ursini, “A comparison of thiol peroxidase mechanisms,” Antioxidants & Redox Signaling, vol. 15, no. 3, pp. 763–780, 2011.
[3]
D. I. Brown and K. K. Griendling, “Nox proteins in signal transduction,” Free Radical Biology and Medicine, vol. 47, no. 9, pp. 1239–1253, 2009.
[4]
T. Finkel, “Signal transduction by reactive oxygen species,” The Journal of Cell Biology, vol. 194, no. 1, pp. 7–15, 2011.
[5]
R. B. Hamanaka and N. S. Chandel, “Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes,” Trends in Biochemical Sciences, vol. 35, no. 9, pp. 505–513, 2010.
[6]
Y. Shimizu and L. M. Hendershot, “Oxidative folding: cellular strategies for dealing with the resultant equimolar production of reactive oxygen species,” Antioxidants & Redox Signaling, vol. 11, no. 9, pp. 2317–2331, 2009.
[7]
B. P. Tu and J. S. Weissman, “Oxidative protein folding in eukaryotes: mechanisms and consequences,” The Journal of Cell Biology, vol. 164, no. 3, pp. 341–346, 2004.
[8]
M. Bertolotti, S. Bestetti, J. M. Garcia-Manteiga et al., “Tyrosine kinase signal modulation: a matter of H2O2 membrane permeability?” Antioxidants & Redox Signaling, 2013.
[9]
G. P. Bienert, A. L. B. M？ller, K. A. Kristiansen et al., “Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes,” The Journal of Biological Chemistry, vol. 282, no. 2, pp. 1183–1192, 2007.
[10]
Z. A. Wood, E. Schr？der, J. Robin Harris, and L. B. Poole, “Structure, mechanism and regulation of peroxiredoxins,” Trends in Biochemical Sciences, vol. 28, no. 1, pp. 32–40, 2003.
[11]
E. M. Hanschmann, M. E. L？nn, L. D. Schütte et al., “Both thioredoxin 2 and glutaredoxin 2 contribute to the reduction of the mitochondrial 2-Cys peroxiredoxin Prx3,” The Journal of Biological Chemistry, vol. 285, no. 52, pp. 40699–40705, 2010.
[12]
E. Zito, “PRDX4, an endoplasmic reticulum-localized peroxiredoxin at the crossroads between enzymatic oxidative protein folding and nonenzymatic protein oxidation,” Antioxidants & Redox Signaling, vol. 18, no. 13, pp. 1666–1674, 2013.
[13]
A. B. Fisher, “Peroxiredoxin 6: a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities,” Antioxidants & Redox Signaling, vol. 15, no. 3, pp. 831–844, 2011.
[14]
L. A. Ralat, Y. Manevich, A. B. Fisher, and R. F. Colman, “Direct evidence for the formation of a complex between 1-cysteine peroxiredoxin and glutathione S-transferase π with activity changes in both enzymes,” Biochemistry, vol. 45, no. 2, pp. 360–372, 2006.
[15]
W. T. Lowther and A. C. Haynes, “Reduction of cysteine sulfinic acid in eukaryotic, typical 2-Cys peroxiredoxins by sulfiredoxin,” Antioxidants & Redox Signaling, vol. 15, no. 1, pp. 99–109, 2011.
[16]
S. G. Rhee and H. A. Woo, “Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger H2O2, and protein chaperones,” Antioxidants & Redox Signaling, vol. 15, no. 3, pp. 781–794, 2011.
[17]
S. G. Rhee, H. A. Woo, I. S. Kil, and S. H. Bae, “Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides,” The Journal of Biological Chemistry, vol. 287, no. 7, pp. 4403–4410, 2012.
[18]
W. Jeong, S. H. Bae, M. B. Toledano, and S. G. Rhee, “Role of sulfiredoxin as a regulator of peroxiredoxin function and regulation of its expression,” Free Radical Biology and Medicine, vol. 53, no. 3, pp. 447–456, 2012.
[19]
Y. H. Noh, J. Y. Baek, W. Jeong, S. G. Rhee, and T. S. Chang, “Sulfiredoxin translocation into mitochondria plays a crucial role in reducing hyperoxidized peroxiredoxin III,” The Journal of Biological Chemistry, vol. 284, no. 13, pp. 8470–8477, 2009.
[20]
S. C. E. Tosatto, V. Bosello, F. Fogolari et al., “The catalytic site of glutathione peroxidases,” Antioxidants & Redox Signaling, vol. 10, no. 9, pp. 1515–1526, 2008.
[21]
R. Brigelius-Flohe and M. Maiorino, “Glutathione peroxidases,” Biochimica Et Biophysica Acta, vol. 1830, no. 5, pp. 3289–3303, 2013.
[22]
M. Bj？rnstedt, J. Xue, W. Huang, B. ？kesson, and A. Holmgren, “The thioredoxin and glutaredoxin systems are efficient electron donors to human plasma glutathione peroxidase,” The Journal of Biological Chemistry, vol. 269, no. 47, pp. 29382–29384, 1994.
[23]
C. Godeas, F. Tramer, F. Micali et al., “Phospholipid hydroperoxide glutathione peroxidase (PHGPx) in rat testis nuclei is bound to chromatin,” Biochemical and Molecular Medicine, vol. 59, no. 2, pp. 118–124, 1996.
[24]
M. Maiorino, A. Roveri, L. Benazzi et al., “Functional interaction of phospholipid hydroperoxide glutathione peroxidase with sperm mitochondrion-associated cysteine-rich protein discloses the adjacent cysteine motif as a new substrate of the selenoperoxidase,” The Journal of Biological Chemistry, vol. 280, no. 46, pp. 38395–38402, 2005.
[25]
F. Ursini, S. Heim, M. Kiess et al., “Dual function of the selenoprotein PHGPx during sperm maturation,” Science, vol. 285, no. 5432, pp. 1393–1396, 1999.
[26]
M. Maiorino, F. Ursini, V. Bosello et al., “The thioredoxin specificity of Drosophila GPx: a paradigm for a peroxiredoxin-like mechanism of many glutathione peroxidases,” Journal of Molecular Biology, vol. 365, no. 4, pp. 1033–1046, 2007.
[27]
S. Toppo, S. Vanin, V. Bosello, and S. C. E. Tosatto, “Evolutionary and structural insights into the multifaceted glutathione peroxidase (Gpx) superfamily,” Antioxidants & Redox Signaling, vol. 10, no. 9, pp. 1501–1514, 2008.
[28]
M. Schuldiner and B. Schwappach, “From rags to riches—the history of the endoplasmic reticulum,” Biochimica et Biophysica Acta, vol. 1833, no. 11, pp. 2389–2391, 2013.
[29]
N. J. Bulleid and L. Ellgaard, “Multiple ways to make disulfides,” Trends in Biochemical Sciences, vol. 36, no. 9, pp. 485–492, 2011.
[30]
E. Gross, C. S. Sevier, N. Heldman et al., “Generating disulfides enzymatically: reaction products and electron acceptors of the endoplasmic reticulum thiol oxidase Ero1p,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 2, pp. 299–304, 2006.
[31]
K. Chen, M. T. Kirber, H. Xiao, Y. Yang, and J. F. Keaney Jr., “Regulation of ROS signal transduction by NADPH oxidase 4 localization,” The Journal of Cell Biology, vol. 181, no. 7, pp. 1129–1139, 2008.
[32]
E. Pedruzzi, C. Guichard, V. Ollivier et al., “NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells,” Molecular and Cellular Biology, vol. 24, no. 24, pp. 10703–10717, 2004.
[33]
R. F. Wu, Z. Ma, Z. Liu, and L. S. Terada, “Nox4-derived H2O2 mediates endoplasmic reticulum signaling through local Ras activation,” Molecular and Cellular Biology, vol. 30, no. 14, pp. 3553–3568, 2010.
[34]
V. K. Kodali and C. Thorpe, “Oxidative protein folding and the Quiescin-sulfhydryl oxidase family of flavoproteins,” Antioxidants & Redox Signaling, vol. 13, no. 8, pp. 1217–1230, 2010.
[35]
T. Ilani, A. Alon, I. Grossman et al., “A secreted disulfide catalyst controls extracellular matrix composition and function,” Science, vol. 341, no. 6141, pp. 74–76, 2013.
[36]
L. A. Rutkevich and D. B. Williams, “Vitamin K epoxide reductase contributes to protein disulfide formation and redox homeostasis within the endoplasmic reticulum,” Molecular Biology of the Cell, vol. 23, no. 11, pp. 2017–2027, 2012.
[37]
C. S. Sevier, “Erv2 and quiescin sulfhydryl oxidases: Erv-domain enzymes associated with the secretory pathway,” Antioxidants & Redox Signaling, vol. 16, no. 8, pp. 800–808, 2012.
[38]
Y. Yang, Y. Song, and J. Loscalzo, “Regulation of the protein disulfide proteome by mitochondria in mammalian cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 26, pp. 10813–10817, 2007.
[39]
R. S. Balaban, S. Nemoto, and T. Finkel, “Mitochondria, oxidants, and aging,” Cell, vol. 120, no. 4, pp. 483–495, 2005.
[40]
M. Giorgio, E. Migliaccio, F. Orsini et al., “Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis,” Cell, vol. 122, no. 2, pp. 221–233, 2005.
[41]
A. A. Rowland and G. K. Voeltz, “Endoplasmic reticulum-mitochondria contacts: function of the junction,” Nature Reviews Molecular Cell Biology, vol. 13, pp. 607–625, 2012.
[42]
K. Araki and K. Inaba, “Structure, mechanism, and evolution of Ero1 family enzymes,” Antioxidants & Redox Signaling, vol. 16, no. 8, pp. 790–799, 2012.
[43]
A. J. Meyer and T. P. Dick, “Fluorescent protein-based redox probes,” Antioxidants & Redox Signaling, vol. 13, no. 5, pp. 621–650, 2010.
[44]
B. Enyedi, P. Várnai, and M. Geiszt, “Redox state of the endoplasmic reticulum is controlled by Ero1l-alpha and intraluminal calcium,” Antioxidants & Redox Signaling, vol. 13, no. 6, pp. 721–729, 2010.
[45]
M. Malinouski, Y. Zhou, V. V. Belousov, D. L. Hatfield, and V. N. Gladyshev, “Hydrogen peroxide probes directed to different cellular compartments,” PLoS ONE, vol. 6, no. 1, Article ID e14564, 2011.
[46]
I. Mehmeti, S. Lortz, and S. Lenzen, “The H2O2-sensitive HyPer protein targeted to the endoplasmic reticulum as a mirror of the oxidizing thiol-disulfide milieu,” Free Radical Biology and Medicine, vol. 53, no. 7, pp. 1451–1458, 2012.
[47]
D. R. Gough and T. G. Cotter, “Hydrogen peroxide: a Jekyll and Hyde signalling molecule,” Cell Death & Disease, vol. 2, no. 10, article e213, 2011.
[48]
G. Groeger, C. Quiney, and T. G. Cotter, “Hydrogen peroxide as a cell-survival signaling molecule,” Antioxidants & Redox Signaling, vol. 11, no. 11, pp. 2655–2671, 2009.
[49]
N. M. Mishina, P. A. Tyurin-Kuzmin, K. N. Markvicheva et al., “Does cellular hydrogen peroxide diffuse or act locally?” Antioxidants & Redox Signaling, vol. 14, no. 1, pp. 1–7, 2011.
[50]
M. B. Toledano, A.-G. Planson, and A. Delaunay-Moisan, “Reining in H2O2 for safe signaling,” Cell, vol. 140, no. 4, pp. 454–456, 2010.
[51]
V. V. Belousov, A. F. Fradkov, K. A. Lukyanov et al., “Genetically encoded fluorescent indicator for intracellular hydrogen peroxide,” Nature Methods, vol. 3, no. 4, pp. 281–286, 2006.
[52]
J. Birk, T. Ramming, A. Odermatt, and C. Appenzeller-Herzog, “Green fluorescent protein-based monitoring of endoplasmic reticulum redox poise,” Frontiers in Genetics, vol. 4, p. 108, 2013.
[53]
C. C. Winterbourn, “Reconciling the chemistry and biology of reactive oxygen species,” Nature Chemical Biology, vol. 4, no. 5, pp. 278–286, 2008.
[54]
Y. S. Bae, S. W. Kang, M. S. Seo et al., “Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor-mediated tyrosine phosphorylation,” The Journal of Biological Chemistry, vol. 272, no. 1, pp. 217–221, 1997.
[55]
M. Sundaresan, Z. X. Yu, V. J. Ferrans, K. Irani, and T. Finkel, “Requirement for generation of H2O2 for platelet-derived growth factor signal transduction,” Science, vol. 270, no. 5234, pp. 296–299, 1995.
[56]
K. Mahadev, A. Zilbering, L. Zhu, and B. J. Goldstein, “Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine phosphatase 1B in vivo and enhances the early insulin action cascade,” The Journal of Biological Chemistry, vol. 276, no. 24, pp. 21938–21942, 2001.
[57]
T. C. Meng, T. Fukada, and N. K. Tonks, “Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo,” Molecular Cell, vol. 9, no. 2, pp. 387–399, 2002.
[58]
M. Reth, “Hydrogen peroxide as second messenger in lymphocyte activation,” Nature Immunology, vol. 3, no. 12, pp. 1129–1134, 2002.
[59]
N. K. Tonks, “Protein tyrosine phosphatases: from genes, to function, to disease,” Nature Reviews Molecular Cell Biology, vol. 7, no. 11, pp. 833–846, 2006.
[60]
H. A. Woo, S. H. Yim, D. H. Shin, D. Kang, D. Y. Yu, and S. G. Rhee, “Inactivation of peroxiredoxin I by phosphorylation allows localized H2O2 accumulation for cell signaling,” Cell, vol. 140, no. 4, pp. 517–528, 2010.
[61]
F. G. Haj, P. J. Verveer, A. Squire, B. G. Neel, and P. I. H. Bastiaens, “Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum,” Science, vol. 295, no. 5560, pp. 1708–1711, 2002.
[62]
K. Palande, O. Roovers, J. Gits et al., “Peroxiredoxin-controlled G-CSF signalling at the endoplasmic reticulum-early endosome interface,” Journal of Cell Science, vol. 124, no. 21, pp. 3695–3705, 2011.
[63]
C. Hetz, “The unfolded protein response: controlling cell fate decisions under ER stress and beyond,” Nature Reviews Molecular Cell Biology, vol. 13, no. 2, pp. 89–102, 2012.
[64]
C. He, H. Zhu, W. Zhang et al., “7-Ketocholesterol induces autophagy in vascular smooth muscle cells through Nox4 and Atg4B,” The American Journal of Pathology, vol. 183, no. 2, pp. 626–637, 2013.
[65]
T. Kakihana, K. Nagata, and R. Sitia, “Peroxides and peroxidases in the endoplasmic reticulum: integrating redox homeostasis and oxidative folding,” Antioxidants & Redox Signaling, vol. 16, no. 8, pp. 763–771, 2012.
[66]
T. J. Tavender, A. M. Sheppard, and N. J. Bulleid, “Peroxiredoxin IV is an endoplasmic reticulum-localized enzyme forming oligomeric complexes in human cells,” Biochemical Journal, vol. 411, no. 1, pp. 191–199, 2008.
[67]
T. Kakihana, K. Araki, S. Vavassori et al., “Dynamic regulation of Ero1alpha and Prx4 localization in the secretory pathway,” The Journal of Biological Chemistry, 2013.
[68]
V. Haridas, J. Ni, A. Meager et al., “Cutting edge: TRANK, a novel cytokine that activates NF-κB and c-Jun N-terminal kinase,” The Journal of Immunology, vol. 161, no. 1, pp. 1–6, 1998.
[69]
Y. Iuchi, F. Okada, S. Tsunoda et al., “Peroxiredoxin 4 knockout results in elevated spermatogenic cell death via oxidative stress,” Biochemical Journal, vol. 419, no. 1, pp. 149–158, 2009.
[70]
D. Y. Jin, H. Z. Chae, S. G. Rhee, and K. T. Jeang, “Regulatory role for a novel human thioredoxin peroxidase in NF-κB activation,” The Journal of Biological Chemistry, vol. 272, no. 49, pp. 30952–30961, 1997.
[71]
A. Matsumoto, A. Okado, T. Fujii et al., “Cloning of the peroxiredoxin gene family in rats and characterization of the fourth member,” FEBS Letters, vol. 443, no. 3, pp. 246–250, 1999.
[72]
A. Okado-Matsumoto, A. Matsumoto, J. Fujii, and N. Taniguchi, “Peroxiredoxin IV is a secretable protein with heparin-binding properties under reduced conditions,” Journal of Biochemistry, vol. 127, no. 3, pp. 493–501, 2000.
[73]
S. Barranco-Medina, J. J. Lázaro, and K. J. Dietz, “The oligomeric conformation of peroxiredoxins links redox state to function,” FEBS Letters, vol. 583, no. 12, pp. 1809–1816, 2009.
[74]
Z. Cao, T. J. Tavender, A. W. Roszak, R. J. Cogdell, and N. J. Bulleid, “Crystal structure of reduced and of oxidized peroxiredoxin IV enzyme reveals a stable oxidized decamer and a non-disulfide-bonded intermediate in the catalytic cycle,” The Journal of Biological Chemistry, vol. 286, no. 49, pp. 42257–42266, 2011.
[75]
T. J. Tavender, J. J. Springate, and N. J. Bulleid, “Recycling of peroxiredoxin IV provides a novel pathway for disulphide formation in the endoplasmic reticulum,” The EMBO Journal, vol. 29, no. 24, pp. 4185–4197, 2010.
[76]
X. Wang, L. Wang, X. Wang, F. Sun, and C.-C. Wang, “Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4,” Biochemical Journal, vol. 441, no. 1, pp. 113–118, 2012.
[77]
Y. Ikeda, R. Ito, H. Ihara, T. Okada, and J. Fujii, “Expression of N-terminally truncated forms of rat peroxiredoxin-4 in insect cells,” Protein Expression and Purification, vol. 72, no. 1, pp. 1–7, 2010.
[78]
T. Ramming and C. Appenzeller-Herzog, “The physiological functions of mammalian endoplasmic oxidoreductin 1: on disulfides and more,” Antioxidants & Redox Signaling, vol. 16, no. 10, pp. 1109–1118, 2012.
[79]
D. Fass, “Hunting for alternative disulfide bond formation pathways: endoplasmic reticulum janitor turns professor and teaches a lesson,” Molecular Cell, vol. 40, no. 5, pp. 685–686, 2010.
[80]
T. J. Tavender and N. J. Bulleid, “Peroxiredoxin IV protects cells from oxidative stress by removing H2O2 produced during disulphide formation,” Journal of Cell Science, vol. 123, no. 15, pp. 2672–2679, 2010.
[81]
E. Zito, E. P. Melo, Y. Yang, ？. Wahlander, T. A. Neubert, and D. Ron, “Oxidative protein folding by an endoplasmic reticulum-localized peroxiredoxin,” Molecular Cell, vol. 40, no. 5, pp. 787–797, 2010.
[82]
E. Zito, H. G. Hansen, G. S. Yeo, J. Fujii, and D. Ron, “Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice,” Molecular Cell, vol. 48, pp. 39–51, 2012.
[83]
Y. Sato, R. Kojima, M. Okumura et al., “Synergistic cooperation of PDI family members in peroxiredoxin 4-driven oxidative protein folding,” Scientific Reports, vol. 3, article 2456, 2013.
[84]
I. Raykhel, H. Alanen, K. Salo et al., “A molecular specificity code for the three mammalian KDEL receptors,” The Journal of Cell Biology, vol. 179, no. 6, pp. 1193–1204, 2007.
[85]
A. Spang, “Retrograde traffic from the Golgi to the endoplasmic reticulum,” Cold Spring Harbor Perspectives in Biology, vol. 5, no. 6, Article ID a013391, 2013.
[86]
V. Bosello-Travain, M. Conrad, G. Cozza et al., “Protein disulfide isomerase and glutathione are alternative substrates in the one Cys catalytic cycle of glutathione peroxidase 7,” Biochimica et Biophysica Acta, vol. 1830, no. 6, pp. 3846–3857, 2013.
[87]
H. Imai and Y. Nakagawa, “Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells,” Free Radical Biology and Medicine, vol. 34, no. 2, pp. 145–169, 2003.
[88]
V. D. Nguyen, M. J. Saaranen, A.-R. Karala et al., “Two endoplasmic reticulum PDI peroxidases increase the efficiency of the use of peroxide during disulfide bond formation,” Journal of Molecular Biology, vol. 406, no. 3, pp. 503–515, 2011.
[89]
L. Wang, L. Zhang, Y. Niu, R. Sitia, and C. C. Wang, “Glutathione peroxidase 7 utilizes hydrogen peroxide generated by Ero1alpha to promote oxidative protein folding,” Antioxidants & Redox Signaling, 2013.
[90]
P. C. Wei, Y. H. Hsieh, M. I. Su et al., “Loss of the oxidative stress sensor NPGPx compromises GRP78 chaperone activity and induces systemic disease,” Molecular Cell, vol. 48, pp. 747–759, 2012.
[91]
M. Gutscher, M. C. Sobotta, G. H. Wabnitz et al., “Proximity-based protein thiol oxidation by H2O2-scavenging peroxidases,” The Journal of Biological Chemistry, vol. 284, no. 46, pp. 31532–31540, 2009.
[92]
A. K. Lappi and L. W. Ruddock, “Reexamination of the role of interplay between glutathione and protein disulfide isomerase,” Journal of Molecular Biology, vol. 409, no. 2, pp. 238–249, 2011.
[93]
P. C. Wei, W. T. Lo, M. I. Su, J. Y. Shew, and W. H. Lee, “Non-targeting siRNA induces NPGPx expression to cooperate with exoribonuclease XRN2 for releasing the stress,” Nucleic Acids Research, vol. 40, no. 1, pp. 323–332, 2012.
[94]
P. C. Wei, Z. F. Wang, W. T. Lo et al., “A cis-element with mixed G-quadruplex structure of NPGPx promoter is essential for nucleolin-mediated transactivation on non-targeting siRNA stress,” Nucleic Acids Research, vol. 41, pp. 1533–1543, 2013.
[95]
S. Li, L. Liu, X. Zhuang et al., “MicroRNAs inhibit the translation of target mRNAs on the endoplasmic reticulum in Arabidopsis,” Cell, vol. 153, no. 3, pp. 562–574, 2013.
[96]
L. Stalder, W. Heusermann, L. Sokol et al., “The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing,” The EMBO Journal, vol. 32, pp. 1115–1127, 2013.
[97]
A. R. Frand and C. A. Kaiser, “Ero1p oxidizes protein disulfide isomerase in a pathway for disulfide bond formation in the endoplasmic reticulum,” Molecular Cell, vol. 4, no. 4, pp. 469–477, 1999.
[98]
B. P. Tu, S. C. Ho-Schleyer, K. J. Travers, and J. S. Weissman, “Biochemical basis of oxidative protein folding in the endoplasmic reticulum,” Science, vol. 290, no. 5496, pp. 1571–1574, 2000.
[99]
C. Appenzeller-Herzog, “Glutathione- and non-glutathione-based oxidant control in the endoplasmic reticulum,” Journal of Cell Science, vol. 124, no. 6, pp. 847–855, 2011.
[100]
F. Hatahet and L. W. Ruddock, “Substrate recognition by the protein disulfide isomerases,” FEBS Journal, vol. 274, no. 20, pp. 5223–5234, 2007.
[101]
C. Appenzeller-Herzog, J. Riemer, B. Christensen, E. S. S？rensen, and L. Ellgaard, “A novel disulphide switch mechanism in Ero1α balances ER oxidation in human cells,” The EMBO Journal, vol. 27, no. 22, pp. 2977–2987, 2008.
[102]
S. N. Radyuk, V. I. Klichko, K. Michalak, and W. C. Orr, “The effect of peroxiredoxin 4 on fly physiology is a complex interplay of antioxidant and signaling functions,” FASEB Journal, vol. 27, pp. 1426–1438, 2013.
[103]
X. Guo, S. Yamada, A. Tanimoto et al., “Overexpression of peroxiredoxin 4 attenuates atherosclerosis in apolipoprotein E knockout mice,” Antioxidants & Redox Signaling, vol. 17, no. 10, pp. 1362–1375, 2012.
[104]
Y. Ding, S. Yamada, K.-Y. Wang et al., “Overexpression of peroxiredoxin 4 protects against high-dose streptozotocin-induced diabetes by suppressing oxidative stress and cytokines in transgenic mice,” Antioxidants & Redox Signaling, vol. 13, no. 10, pp. 1477–1490, 2010.
[105]
A. Nabeshima, S. Yamada, X. Guo et al., “Peroxiredoxin 4 protects against nonalcoholic steatohepatitis and type 2 diabetes in a nongenetic mouse model,” Antioxidants & Redox Signaling, 2013.
[106]
M. Bertolotti, S. H. Yim, J. M. Garcia-Manteiga et al., “B- to plasma-cell terminal differentiation entails oxidative stress and profound reshaping of the antioxidant responses,” Antioxidants & Redox Signaling, vol. 13, no. 8, pp. 1133–1144, 2010.
[107]
R. Vené, L. Delfino, P. Castellani et al., “Redox remodeling allows and controls B-cell activation and differentiation,” Antioxidants & Redox Signaling, vol. 13, no. 8, pp. 1145–1155, 2010.
[108]
R. E. Hansen, M. Otsu, I. Braakman, and J. R. Winther, “Quantifying changes in the cellular thiol-disulfide status during differentiation of B cells into antibody-secreting plasma cells,” International Journal of Cell Biology, vol. 2013, Article ID 898563, 9 pages, 2013.
[109]
D. Peng, T. Hu, M. Soutto, A. Belkhiri, A. Zaika, and W. El-Rifai, “Glutathione peroxidase 7 has potential tumour suppressor functions that are silenced by location-specific methylation in oesophageal adenocarcinoma,” Gut. In press.
[110]
D. F. Peng, M. Razvi, H. Chen et al., “DNA hypermethylation regulates the expression of members of the Mu-class glutathione S-transferases and glutathione peroxidases in Barrett's adenocarcinoma,” Gut, vol. 58, no. 1, pp. 5–15, 2009.
[111]
D. F. Peng, A. Belkhiri, T. L. Hu et al., “Glutathione peroxidase 7 protects against oxidative DNA damage in oesophageal cells,” Gut, vol. 61, no. 9, pp. 1250–1260, 2012.
[112]
D. M. Battle, S. D. Gunasekara, G. R. Watson et al., “Expression of the endoplasmic reticulum oxidoreductase Ero1alpha in gastro-intestinal cancer reveals a link between homocysteine and oxidative protein folding,” Antioxidants & Redox Signaling, vol. 19, no. 1, pp. 24–35, 2013.
[113]
J. Han, S. H. Back, J. Hur et al., “ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death,” Nature Cell Biology, vol. 15, pp. 481–490, 2013.
[114]
G. Li, M. Mongillo, K.-T. Chin et al., “Role of ERO1-α-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis,” The Journal of Cell Biology, vol. 186, no. 6, pp. 783–792, 2009.
[115]
S. J. Marciniak, C. Y. Yun, S. Oyadomari et al., “CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum,” Genes & Development, vol. 18, no. 24, pp. 3066–3077, 2004.
