JOURNAL BROWSE
Search
Advanced SearchSearch Tips
The Roles of Peroxiredoxin and Thioredoxin in Hydrogen Peroxide Sensing and in Signal Transduction
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : Molecules and Cells
  • Volume 39, Issue 1,  2016, pp.65-71
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2349
 Title & Authors
The Roles of Peroxiredoxin and Thioredoxin in Hydrogen Peroxide Sensing and in Signal Transduction
Netto, Luis E.S.; Antunes, Fernando;
  PDF(new window)
 Abstract
A challenge in the redox field is the elucidation of the molecular mechanisms, by which mediates signal transduction in cells. This is relevant since redox pathways are disturbed in some pathologies. The transcription factor OxyR is the sensor in bacteria, whereas Cys-based peroxidases are involved in the perception of this oxidant in eukaryotic cells. Three possible mechanisms may be involved in signaling that are not mutually exclusive. In the simplest pathway, signals through direct oxidation of the signaling protein, such as a phosphatase or a transcription factor. Although signaling proteins are frequently observed in the oxidized state in biological systems, in most cases their direct oxidation by is too slow ( range) to outcompete Cys-based peroxidases and glutathione. In some particular cellular compartments (such as vicinity of NADPH oxidases), it is possible that a signaling protein faces extremely high concentrations, making the direct oxidation feasible. Alternatively, high levels can hyperoxidize peroxiredoxins leading to local building up of that then could oxidize a signaling protein (floodgate hypothesis). In a second model, oxidizes Cys-based peroxidases that then through thiol-disulfide reshuffling would transmit the oxidized equivalents to the signaling protein. The third model of signaling is centered on the reducing substrate of Cys-based peroxidases that in most cases is thioredoxin. Is this model, peroxiredoxins would signal by modulating the thioredoxin redox status. More kinetic data is required to allow the identification of the complex network of thiol switches.
 Keywords
;Peroxiredoxin;signal transduction;thiol;thiol-disulfide exchange;thioredoxin;
 Language
English
 Cited by
1.
Overview on Peroxiredoxin,;

Molecules and Cells, 2016. vol.39. 1, pp.1-5 crossref(new window)
1.
New Challenges to Study Heterogeneity in Cancer Redox Metabolism, Frontiers in Cell and Developmental Biology, 2017, 5  crossref(new windwow)
2.
Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation, Redox Biology, 2016, 10, 233  crossref(new windwow)
3.
Oxidative stress, metabolomics profiling, and mechanism of local anesthetic induced cell death in yeast, Redox Biology, 2017, 12, 139  crossref(new windwow)
4.
Hyperoxidation of Peroxiredoxins: Gain or Loss of Function?, Antioxidants & Redox Signaling, 2017  crossref(new windwow)
5.
The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage, Frontiers in Physiology, 2017, 8  crossref(new windwow)
6.
The Role of Peroxiredoxins in the Transduction of H2O2 Signals, Antioxidants & Redox Signaling, 2017  crossref(new windwow)
7.
Peroxiredoxin 1 - an antioxidant enzyme in cancer, Journal of Cellular and Molecular Medicine, 2017, 21, 1, 193  crossref(new windwow)
8.
Quantitative biology of hydrogen peroxide signaling, Redox Biology, 2017, 13, 1  crossref(new windwow)
9.
Disulfide Stress Targets Modulators of Excitotoxicity in Otherwise Healthy Brains, Neurochemical Research, 2016, 41, 10, 2763  crossref(new windwow)
10.
An Atlas of Peroxiredoxins Created Using an Active Site Profile-Based Approach to Functionally Relevant Clustering of Proteins, PLOS Computational Biology, 2017, 13, 2, e1005284  crossref(new windwow)
11.
Thioredoxin and redox signaling: Roles of the thioredoxin system in control of cell fate, Archives of Biochemistry and Biophysics, 2017, 617, 101  crossref(new windwow)
12.
Mitochondrial peroxiredoxins are essential in regulating the relationship between Drosophila immunity and aging, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2017, 1863, 1, 68  crossref(new windwow)
13.
Cardiac Cell Senescence and Redox Signaling, Frontiers in Cardiovascular Medicine, 2017, 4  crossref(new windwow)
14.
Overview on Peroxiredoxin, Molecules and Cells, 2016, 39, 1, 1  crossref(new windwow)
15.
Experimentally Dissecting the Origins of Peroxiredoxin Catalysis, Antioxidants & Redox Signaling, 2017  crossref(new windwow)
16.
The Conundrum of Hydrogen Peroxide Signaling and the Emerging Role of Peroxiredoxins as Redox Relay Hubs, Antioxidants & Redox Signaling, 2017  crossref(new windwow)
17.
Novel insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit F, Biochimica et Biophysica Acta (BBA) - General Subjects, 2017  crossref(new windwow)
18.
Targeting and synergistic action of an antifungal peptide in an antibiotic drug-delivery system, Journal of Controlled Release, 2017, 256, 46  crossref(new windwow)
19.
Redox stress and signaling during vertebrate embryonic development: Regulation and responses, Seminars in Cell & Developmental Biology, 2017  crossref(new windwow)
20.
Peroxisomes as Modulators of Cellular Protein Thiol Oxidation: A New Model System, Antioxidants & Redox Signaling, 2017  crossref(new windwow)
21.
The Peroxisome-Mitochondria Connection: How and Why?, International Journal of Molecular Sciences, 2017, 18, 6, 1126  crossref(new windwow)
22.
Catalytic Thr or Ser Residue Modulates Structural Switches in 2-Cys Peroxiredoxin by Distinct Mechanisms, Scientific Reports, 2016, 6, 1  crossref(new windwow)
23.
Localized redox relays as a privileged mode of cytoplasmic hydrogen peroxide signaling, Redox Biology, 2017, 12, 233  crossref(new windwow)
24.
Mitochondrial ROS versus ER ROS: Which Comes First in Myocardial Calcium Dysregulation?, Frontiers in Cardiovascular Medicine, 2016, 3  crossref(new windwow)
25.
PRDX2 in Myocyte Hypertrophy and Survival is Mediated by TLR4 in Acute Infarcted Myocardium, Scientific Reports, 2017, 7, 1  crossref(new windwow)
 References
1.
Abbasi, A., Corpeleijn, E., Gansevoort, R.T., Gans, R.O.B., Struck, J., Schulte, J., Hillege, H.L., van der Harst, P., Stolk, R.P., Navis, G., et al. (2014). Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study. Diabetologia 57, 1842-1849. crossref(new window)

2.
Ahsan, M.K., Lekli, I., Ray, D., Yodoi, J., and Das, D.K. (2009). Redox regulation of cell survival by the thioredoxin superfamily: an implication of redox gene therapy in the heart Antioxid. Redox Signal. 11, 2741-2758. crossref(new window)

3.
Aslund, F., Zheng, M., Beckwith, J., and Storz, G. (1999). Regulation of the OxyR transcription factor by hydrogen peroxide and the cellular thiol-disulfide status. Proc. Natl. Acad. Sci. USA 96, 6161-6165. crossref(new window)

4.
Berndt, C., Lillig, C.H., and Holmgren, A. (2007). Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: implications for diseases in the cardiovascular system. Am. J. Physiol. Heart Circ. Physiol. 292, H1227-H1236.

5.
Biteau, B., Labarre, J., and Toledano, M.B. (2003). ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin. Nature 425, 980-984. crossref(new window)

6.
Boisnard, S., Lagniel, G., Garmendia-Torres, C. Molin, M., Boy-Marcotte, E., Jacquet, M., Toledano, M.B., Labarre, J., and Chedin, S. (2009). $H_2O_2$ activates the nuclear localization of Msn2 and Maf1 through thioredoxins in Saccharomyces cerevisiae. Eukaryot. Cell 8, 1429-1438. crossref(new window)

7.
Boronat, S., Domenech, A., Paulo, E., Calvo, I.A., Garcia-Santamarina, S., Garcia, P., Encinar Del Dedo, J., Barcons, A., Serrano, E., Carmona, M., et al. (2014). Thiol-based $H_2O_2$ signalling in microbial systems. Redox Biol. 2, 395-399 crossref(new window)

8.
Branco, M.R., Marinho, H.S., Cyrne, L., and Antunes, F. (2004). Decrease of $H_2O_2$ plasma membrane permeability during adaptation to $H_2O_2$ in Saccharomyces cerevisiae. J. Biol. Chem. 279, 6501-6506.

9.
Brito, P.M., and Antunes, F. (2014). Estimation of kinetic parameters related to biochemical interactions between hydrogen peroxide and signal transduction proteins. Front Chem. 2, 82.

10.
Brown, J.D., Day, A.M., Taylor, S.R., Tomalin, L.E., Morgan, B.A., and Veal, E.A. (2013). A peroxiredoxin promotes $H_2O_2$ signaling and oxidative stress resistance by oxidizing a thioredoxin family protein. Cell Rep. 5, 1425-1435. crossref(new window)

11.
Calvo, I.A., Boronat, S., Domenech, A., Garcia-Santamarina, S., Ayte, J., and Hidalgo, E. (2013). Dissection of a redox relay:$H_2O_2$-dependent activation of the transcription factor Pap1 through the peroxidatic Tpx1-thioredoxin cycle. Cell Rep. 5, 1413-1424. crossref(new window)

12.
Cao, J., Schulte, J., Knight, A., Leslie, N.R., Zagozdzon, A., Bronson, R., Manevich, Y., Beeson, C., and Neumann, C.A. (2009).Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity. EMBO J. 28, 1505-1517. crossref(new window)

13.
Chae, H.Z., Chung, S.J., and Rhee, S.G. (1994).Thioredoxindependent peroxide reductase from yeast. J. Biol. Chem. 269, 27670-27678.

14.
Chen, K., Kirber, M.T., Xiao, H., Yang, Y., and Keaney, J.F. (2008). Regulation of ROS signal transduction by NADPH oxidase 4 localization. J. Cell Biol. 181, 1129-1139. crossref(new window)

15.
Dagnell, M., Frijhoff, J., Pader, I., Augsten, M., Boivin, B., Xu, J., Mandal, P.K., Tonks, N.K., Hellberg, C., Conrad, M., et al. (2013). Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-receptor tyrosine kinase signaling. Proc. Natl. Acad. Sci. USA 110, 13398-13403. crossref(new window)

16.
Day, A.M., Brown, J.D., Taylor, S.R., Rand, J.D., Morgan, B.A., and Veal, E.A. (2012). Inactivation of a peroxiredoxin by hydrogen peroxide is critical for thioredoxin-mediated repair of oxidized proteins and cell survival .Mol. Cell 45, 398-408. crossref(new window)

17.
Delaunay, A., Pflieger, D., Barrault, M. B., Vinh, J., and Toledano, M. B. (2002). A thiol peroxidase is an $H_2O_2$ receptor and redoxtransducer in gene activation. Cell 111, 471-481. crossref(new window)

18.
Denu, J.M., and Tanner, K.G. (1998). Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation. Biochemistry 37, 5633-5642. crossref(new window)

19.
Du, Y., Zhang, H., Zhang, X., Lu, J., and Holmgren, A. (2013). Thioredoxin 1 is inactivated due to oxidation induced by peroxiredoxin under oxidative stress and reactivated by the glutaredoxin system. J. Biol. Chem. 288, 32241-32247. crossref(new window)

20.
Ferrer-Sueta, G., Manta, B., Botti, H., Radi, R., Trujillo, M., and Denicola, A. (2011). Factors affecting protein thiol reactivity and specificity in peroxide reduction. Chem. Res. Toxicol. 24, 434-450. crossref(new window)

21.
Fomenko, D.E., Koc, A., Agisheva, N., Jacobsen, M., Kaya, A., Malinouski, M., Rutherford, J.C., Siu, K.L., Jin, D.Y., Winge, D.R., et al. (2011). Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide. Proc. Natl. Acad. Sci. USA 108, 2729-2734. crossref(new window)

22.
Gutscher, M., Sobotta, M.C., Wabnitz, G.H., Ballikaya, S., Meyer, A.J., Samstag, Y., and Dick, T.P.(2009) Proximity-based protein thiol oxidation by $H_2O_2$-scavenging peroxidases. J. Biol. Chem. 284, 31532-31540. crossref(new window)

23.
Hall, A., Nelson, K., Poole, L.B., and Karplus, P.A. (2011). Structurebased insights into the catalytic power and conformational dexterity of peroxiredoxins. Antioxid. Redox Signal. 15, 795-815. crossref(new window)

24.
Hayashi, T., Ueno, Y., and Okamoto, T. (1993). Oxidoreductive regulation of nuclear factor kappa B. Involvement of a cellular reducing catalyst thioredoxin. J. Biol. Chem. 268, 11380-11388.

25.
Harald, H.H.W., Schmidt, R.S., Vollbracht, C., Paulsen, G., Riley, D., Daiber, A., and Cuadrado, A. (2015). Antioxidants in translational medicine. Antioxid. Redox Signal. 10, 1130-1143.

26.
Irwin, M.E., Rivera-Del Valle, N., and Chandra, J. (2013). Redox control of leukemia: from molecular mechanisms to therapeutic opportunities Antioxid. Redox Signal. 18, 1349-1383 crossref(new window)

27.
Jang, H.H., Lee, K.O., Chi, Y.H., Jung, B.G., Park, S.K., Park, J.H., Lee, J.R., Lee, S.S., Moon, J.C., Yun, J. W., et al. (2004). Two enzymes in one: two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function. Cell 117, 625-635 crossref(new window)

28.
Jarvis, R.M., Hughes, S.M., and Ledgerwood, E.C. (2012). Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells. Free Radic. Biol. Med. 53, 1522-1530. crossref(new window)

29.
Jones, D.P. (2006). Redefining oxidative stress. Antioxid. Redox Signal. 8, 1865-1879. crossref(new window)

30.
Kaszubska, W., Falls, H.D., Schaefer, V.G., Haasch, D., Frost, L., Hessler, P., Kroeger, P.E., White, D.W., Jirousek, M.R., and Trevillyan, J.M. (2002). Protein tyrosine phosphatase 1B negatively regulates leptin signaling in a hypothalamic cell line. Mol. Cell. Endocrinol. 195, 109-118. crossref(new window)

31.
Krapfenbauer, K., Engidawork, E., Cairns, N., Fountoulakis, M., and Lubec, G. (2003). Aberrant expression of peroxiredoxin subtypes in neurodegenerative disorders. Brain Res. 967, 152-160. crossref(new window)

32.
Kwon, J., Lee, S.R., Yang, K.S., Ahn, Y., Kim, Y.J., Stadtman, E.R., and Rhee, S.G. (2004). Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors. Proc. Natl. Acad. Sci. USA 101, 16419-16424. crossref(new window)

33.
Lee, S.R., Kwon, K.S., Kim, S.R., and Rhee, S.G. (1998). Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J. Biol. Chem. 273, 15366-15372. crossref(new window)

34.
Lee, C., Lee, S.M., Mukhopadhyay, P., Kim, S.J., Lee, S.C., Ahn, W.S., Yu, M.H., Storz, G., and Ryu, S.E. (2004). Redox regulation of OxyR requires specific disulfide bond formation involving a rapid kinetic reaction path. Nat. Struct. Mol. Biol. 11, 1179-1185. crossref(new window)

35.
Lee, S., Kim, S.M., and Lee, R.T. (2013). Thioredoxin and thioredoxin target proteins: from molecular mechanisms to functional significance. Antioxid. Redox Signal. 18, 1165-1207 crossref(new window)

36.
Little, C., and O'Brien, P.J. (1969). Mechanism of peroxideinactivation of the sulphydryl enzyme glyceraldehyde-3-phophate dehydrogenase. Eur. J. Biochem.10, 533-538.

37.
MacDiarmid, C.W., Taggart, J., Kerdsomboon, K., Kubisiak, M., Panascharoen, S., Schelble, K., and Eide, D.J. (2013). Peroxiredoxin chaperone activity is critical for protein homeostasis in zinc-deficient yeast. J. Biol. Chem. 288, 31313-31327. crossref(new window)

38.
Mahadev, K., Zilbering, A., Zhu, L., and Goldstein, B. J. (2001). Insulin-stimulated hydrogen peroxide reversibly inhibits proteintyrosine phosphatase 1b in vivo and enhances the early insulin action cascade. J. Biol. Chem. 276, 21938-21942. crossref(new window)

39.
Marinho, H.S., Real, C., Cyrne, L., Soares, H., and Antunes, F. (2014). Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol. 2, 535-562. crossref(new window)

40.
Matthews, J.R., Wakasugi, N., Virelizier, J.L., Yodoi, J., and Hay, R.T. (1992). Thioredoxin regulates the DNA binding activity of NF-${\kappa}B$ by reduction of a disulphide bond involving cysteine 62. Nucleic Acids Res. 20, 3821-3830. crossref(new window)

41.
Meng, T., Fukada, T., and Tonks, N.K. (2002). Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol. Cell 9, 387-399. crossref(new window)

42.
Meyer, Y., Buchanan, B.B., Vignols, F., and Reichheld, J.P. (2009). Thioredoxins and glutaredoxins: unifying elements in redox biology. Annu. Rev. Genet. 43, 335-367. crossref(new window)

43.
Miller, E.W., Dickinson, B.C., and Chang, C.J. (2010). Aquaporin-3 mediates hydrogen peroxide uptake to regulate downstream intracellular signaling. Proc. Natl. Acad. Sci. USA 107, 15681-15686. crossref(new window)

44.
Mishina, N.M., Tyurin-Kuzmin, P.A., Markvicheva, K.N., Vorotnikov, A.V., Tkachuk, V.A., Laketa, V., et al. (2011). Does cellular hydrogen peroxide diffuse or act locally? Antioxid. Redox Signal. 14, 1-7. crossref(new window)

45.
Nelson, K.J., Knutson, S.T., Soito, L., Klomsiri, C., Poole, L.B., and Fetrow, J.S. (2011). Analysis of the peroxiredoxin family: using active-site structure and sequence information for global classification and residue analysis. Proteins 79, 947-964. crossref(new window)

46.
Netto, L.E.S., Chae, H.Z., Kang, S.W., Rhee, S.G., and Stadtman, E.R. (1996). Removal of hydrogen peroxide by thiol-specific antioxidant enzyme (TSA) is involved with its antioxidant properties. TSA possesses thiol peroxidase activity. J. Biol. Chem. 271, 15315-15321. crossref(new window)

47.
Netto, L.E.S., Oliveira, M.A., Tairum-Jr, C., and da Silva Neto, J.F. (2015). Conferring specificity in redox pathways by enzymatic thiol/disulfide exchange reactions. Free Radic. Res. 16, 1-99.

48.
Nystrom, T., Yang, J., and Molin, M. (2012). Peroxiredoxins, gerontogenes linking aging to genome instability and cancer. Genes Dev. 26, 2001-2008. crossref(new window)

49.
Ogusucu, R., Rettori, D., Munhoz, D.C., Netto, L.E.S., and Augusto, O. (2007). Reactions of yeast thioredoxin peroxidases I and II with hydrogen peroxide and peroxynitrite: rate constants by competitive kinetics. Free Radic. Biol. Med. 42, 326-334. crossref(new window)

50.
Oliveira, M.A., Discola, K.F., Alves, S. V., Medrano, F. J., Guimaraes, B.G., and Netto, L.E.S. (2010). Insights into the specificity of thioredoxin reductase-thioredoxin interactions. A structural and functional investigation of the yeast thioredoxin system. Biochemistry 49, 3317-3326. crossref(new window)

51.
Palde, P.B., and Carroll, K.S. (2015). A universal entropy-driven mechanism for thioredoxin-target recognition. Proc. Natl. Acad. Sci. USA 112, 7960-7965. crossref(new window)

52.
Parsonage, D., Youngblood, D.S., Sarma, G.N., Wood, Z.A., Karplus, P.A., and Poole, L.B. (2005). Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin. Biochemistry 44, 10583-10592. crossref(new window)

53.
Parsons, Z.D., and Gates, K.S. (2013). Thiol-dependent recovery of catalytic activity from oxidized protein tyrosine phosphatases. Biochemistry 52, 6412-6423. crossref(new window)

54.
Paulsen, C.E., Truong, T.H., Garcia, F.J., Homann, A., Gupta, V., Leonard, S.E., and Carrol, K.S. (2012). Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity. Nat. Chem. Biol. 8, 57-64.

55.
Pedroso, N., Matias, A.C., Cyrne, L., Antunes, F., Borges, C., Malho, R., de Almeida, R.F.M., Herrero, E., Marinho, H.S. (2009). Modulation of plasma membrane lipid profile and microdomains by $H_2O_2$ in Saccharomyces cerevisiae. Free Radic. Biol. Med. 46, 289-298. crossref(new window)

56.
Peralta, D., Bronowska, A.K., Morgan, B., Doka, E., Van Laer, K., Nagy, P., Grater, F., and Dick, T.P. (2015). A proton relay enhances $H_2O_2$ sensitivity of GAPDH to facilitate metabolic adaptation. Nat. Chem. Biol. 11, 156-163. crossref(new window)

57.
Peskin, A.V., Low, F.M., Paton, L.N., Maghzal, G.J., Hampton, M.B., and Winterbourn, C.C. (2007). The high reactivity of peroxiredoxin 2 with $H_2O_2$ is not reflected in its reaction with other oxidants and thiol reagents. J. Biol. Chem. 282, 11885-11892. crossref(new window)

58.
Peskin, A. V., Pace, P.E., Behring, J.B., Paton, L. N., Soethoudt, M., Bachschmid, M.M., and Winterbourn, C.C. (2016). Glutathionylation of the active site cysteines of peroxiredoxin 2 and recycling by glutaredoxin. J. Biol. Chem. [Epub ahead of print]

59.
Rawat, S.J., Creasy, C.L., Peterson, J.R., and Chernoff, J. (2013). The tumor suppressor Mst1 promotes changes in the cellular redox state by phosphorylation and inactivation of peroxiredoxin-1 protein. J. Biol. Chem. 288, 8762-8771. crossref(new window)

60.
Ragu, S., Dardalhon, M., Sharma, S., Iraqui, I, Buhagiar-Labarchede, G., Grondin, V., Kienda, G., Vernis, L, Chanet, R., Kolodner, R.D., et al. (2014). Loss of the thioredoxin reductase Trr1 suppresses the genomic instability of peroxiredoxin tsa1 mutants. PLoS One 9, e108123. crossref(new window)

61.
Rhee, S. G., and Woo, H. A. (2011) Multiple functions of peroxiredoxins:peroxidases, sensors and regulators of the intracellular messenger $H_2O_2$, and protein chaperones. Antioxid. Redox Signal. 15, 781-794. crossref(new window)

62.
Rhee, S.G., Woo, H.A., Kil, I.S., and Bae, S.H. (2012). Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides J. Biol. Chem. 287, 4403-4410. crossref(new window)

63.
Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K., and Ichijo, H. (1998). Mammalian thioredoxin is a direct inhibitor of apoptosis signal‐regulating kinase (ASK). EMBO J. 17, 2596-2606. crossref(new window)

64.
Schroder, K., Zhang, M., Benkhoff, S., Mieth, A., Pliquett, R., Kosowski, J., Kruse, C., Luedike, P., Michaelis, U.R., Weissmann, N., et al. (2012). Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase. Circ. Res. 110, 1217-1225. crossref(new window)

65.
Sies, H. (2014). Role of metabolic $H_2O_2$ generation: redox signaling and oxidative stress. J. Biol. Chem. 289, 8735-8741. crossref(new window)

66.
Seidler, N.W. (2013). GAPDH: Biological Properties and Diversity. Vol. 985 (Springer).

67.
Sobotta, M.C., Liou, W., Stocker, S., Talwar, D., Oehler, M., Ruppert, T., Scharf, A.N., and Dick, T.P. (2015). Peroxiredoxin-2 and STAT3 form a redox relay for $H_2O_2$ signaling. Nat. Chem. Biol. 11, 64-70.

68.
Tachibana, T., Okazaki, S., Murayama, A., Naganuma, A., Nomoto, A., and Kuge, S. (2009). A major peroxiredoxin-induced activation of Yap1 transcription factor is mediated by reduction sensitive disulfide bonds and reveals a low level of transcriptional activation. J. Biol. Chem. 284, 4464-4472. crossref(new window)

69.
Tairum Jr., C.A., de Oliveira, M.A., Horta, B.B., Zara, F.J., and Netto, L.E.S. (2012). Disulfide biochemistry in 2-cys peroxiredoxin: requirement of Glu50 and Arg146 for the reduction of yeast Tsa1 by thioredoxin. J. Mol. Biol. 424, 28-41. crossref(new window)

70.
Tanner, J.J., Parsons, Z.D., Cummings, A.H., Zhou, H., and Gates, K.S. (2011). Redox regulation of protein tyrosine phosphatases:structural and chemical aspects. Antioxid. Redox Signal. 15, 77-97. crossref(new window)

71.
Toledo, J.C., Audi, R., Ogusucu, R., Monteiro, G., Netto, L.E.S., and Augusto, O. (2011). Horseradish peroxidase compound I as a tool to investigate reactive protein-cysteine residues: from quantification to kinetics. Free Radic. Biol. Med. 50, 1032-1038. crossref(new window)

72.
Trujillo, M., Clippe, A., Manta, B., Ferrer-Sueta, G., Smeets, A., Declercq, J.P., Knoops, B., and Radi, R. (2007). Pre-steady state kinetic characterization of human peroxiredoxin 5: taking advantage of Trp84 fluorescence increase upon oxidation. Arch. Biochem. Biophys. 467, 95-106. crossref(new window)

73.
Turner-Ivey, B., Manevich, Y., Schulte, J., Kistner-Griffin, E., Jezierska-Drutel, A., Liu, Y., and Neumann, C.A. (2013). Role for Prdx1 as a specific sensor in redox-regulated senescence in breast cancer. Oncogene 32, 5302-5314. crossref(new window)

74.
Veal, E.A., Ross, S.J., Malakasi, P., Peacock, E., and Morgan, B.A. (2003). Ybp1 is required for the hydrogen peroxide-induced oxidation of the Yap1 transcription factor. J. Biol. Chem. 278, 30896-30904. crossref(new window)

75.
Watson, W.H., Pohl, J., Montfort, W.R., Stuchlik, O., Reed, M.S., Powis, G., and Jones, D.P. (2003). Redox potential of human thioredoxin 1 and identification of a second dithiol/disulfide motif. J. Biol. Chem. 278, 33408-33415. crossref(new window)

76.
Winterbourn, C.C. (2008). Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol. 4, 278-286. crossref(new window)

77.
Winterbourn, C.C., and Hampton, M.B. (2008). Thiol chemistry and specificity in redox signaling. Free Radic. Biol. Med. 45, 549-561. crossref(new window)

78.
Winterbourn, C.C., and Metodiewa, D. (1999). Reactivity of biologically important thiol compounds with superoxide and hydrogen peroxide. Free Radic. Biol. Med. 27, 322-328. crossref(new window)

79.
Woo, H.A., Yim, S.H., Shin, D.H., Kang, D., Yu, D.Y., and Rhee, S.G. (2010). Inactivation of peroxiredoxin I by phosphorylation allows localized $H_2O_2$ accumulation for cell signaling. Cell 140, 517-528. crossref(new window)

80.
Wood, Z.A., Poole, L.B., and Karplus, P.A. (2003). Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling .Science 300, 650-653. crossref(new window)

81.
Ying, J., Clavreul, N., Sethuraman, M., Adachi, T., and Cohen, R.A. (2007). Thiol oxidation in signaling and response to stress: detection and quantification of physiological and pathophysiological thiol modifications. Free Radic. Biol. Med 43, 1099-1108. crossref(new window)