Abstract

The action of many exogenous factors as well as disturbed metabolic processes of cells contribute to the increased production of oxidants, which leads to redox imbalance and, as a consequence, metabolic changes, including death or tumor transformation of cells. However, each cell is equipped with antioxidants to prevent this type of situation.One of the antioxidant systems functioning in cells is the thioredoxin dependent system, which includes thioredoxin (Trx), thioredoxin reductase (TrxR) and thioredoxin peroxidase (TPx), which have the ability to reduce oxidized forms of cell components at the expense of nicotinamidoadenine dinucleotide phosphate (NADPH). This effect results from the spatial structure of Trx and TrxR, which allows the formation of an intramolecular disulfide bridge within the thioredoxin molecule and two intermolecular selenesulfide bridges within the thioredoxin reductase dimer. Another, equally important function of the thioredoxin-dependent system is to regulate the expression of many proteins through factors such as NFκB transcription factor and apoptosis regulating kinase (ASK-1), which trigger cascades of metabolic transformations ultimately leading to cell proliferation or apoptosis. The increase in expression /activity of Trx-dependent system components is observed in the development of many cancers. Therefore, the search for selective thioredoxin or thioredoxin reductase inhibitors is currently one of the main research directions in cancer pharmacotherapy. It has been shown that many naturally occurring polyphenolic compounds of natural origin with antioxidant activity (e.g. quercetin or curcumin) inactivate the Trx-dependent system. At the same time, a number of synthetic compounds, including complex compounds, that are used in cancer therapy (e.g. cisplatin, auranofin, gadolinium motexafin) also inhibit the action of the thioredoxin system.

References

• 1. Ahsan M.K., Lekli I., Ray D., Yodoi J., Das D.K.: Redox regulationof cell survival by the thioredoxin superfamily: An implicationof redox gene therapy in the heart. Antioxid. Redox Signal.,2009; 11: 2741–2758
  Google Scholar
• 2. An N., Kang Y.: Thioredoxin and hematologic malignancies. W:Advances in Cancer Research, t. 122, red.: D.M. Townsend, K.D. Tew.Academic Press, London, 2014, 245–279
  Google Scholar
• 3. Arnér E.S.: Focus on mammalian thioredoxin reductases – importantselenoproteins with versatile functions. Biochim. Biophys.Acta, 2009; 1790: 495–526
  Google Scholar
• 4. Arnér E.S.: Selenocysteine insertion and reactivity: Mammalianthioredoxin reductases in relation to cellular redox signaling. W:Cellular Implications of Redox Signaling, red.: C. Gitler, A. Danon.Imperial College Press, London 2003, 27–45
  Google Scholar
• 5. Avval F.Z., Holmgren A.: Molecular mechanisms of thioredoxinand glutaredoxin as hydrogen donors for Mammalian s phase ribonucleotidereductase. J. Biol. Chem., 2009; 284: 8233–8240
  Google Scholar
• 6. Baker A.F., Adab K.N., Raghunand N., Chow H., Stratton S.P.,Squire S.W., Boice M., Pestano L.A., Kirkpatrick D.L., Dragovich T.:A phase IB trial of 24-hour intravenous PX-12, a thioredoxin-1 inhibitor,in patients with advanced gastrointestinal cancers. Invest.New Drugs, 2013; 31: 631–641
  Google Scholar
• 7. Baker A.F., Dragovich T., Tate W.R., Ramanathan R.K., Roe D.,Hsu C.H., Kirkpatrick D.L., Powis G.: The antitumor thioredoxin-1inhibitor PX-12 (1-methylpropyl 2-imidazolyl disulfide) decreasesthioredoxin-1 and VEGF levels in cancer patient plasma. J. Lab.Clin. Med., 2006; 147: 83–90
  Google Scholar
• 8. Berdicevsky I., Kaufman G., Newman D.J., Horwitz B.A.: Preliminarystudy of activity of the thioredoxin inhibitor pleurotinagainst Trichophyton mentagrophytes: A novel anti-dermatophytepossibility. Mycoses, 2009; 52: 313–317
  Google Scholar
• 9. Berndt C., Lillig C.H., Holmgren A.: Thioredoxins and glutaredoxinsas facilitators of protein folding. Biochim. Biophys. Acta,2008; 1783: 641–650
  Google Scholar
• 10. Bignon E., Allega M.F., Lucchetta M., Tiberti M., Papaleo E.:Computational structural biology of S-nitrosylation of cancer targets.Front. Oncol., 2018; 8: 272
  Google Scholar
• 11. Bilska A., Kryczyk A., Włodek L.: Różne oblicza biologicznej roliglutationu. Postępy Hig. Med. Dośw., 2007; 61: 438–453
  Google Scholar
• 12. Brandstaedter C., Fritz-Wolf K., Weder S., Fischer M., HeckerB., Rahlfs S., Becker K.: Kinetic characterization of wild-type andmutant human thioredoxin glutathione reductase defines its reactionand regulatory mechanisms., FEBS J., 2018; 285; 542–558
  Google Scholar
• 13. Cai W., Zhang B., Duan D., Wu J., Fang J.: Curcumin targetingthe thioredoxin system elevates oxidative stress in HeLa cells.Toxicol. Appl. Pharmacol., 2012; 262: 341–348
  Google Scholar
• 14. Chen X., Tang W., Liu S., Yu L., Chen Z.: Thioredoxin-1 phosphorylatedat T100 is needed for its anti-apoptotic activity in HepG2cancer cells. Life Sci., 2010; 87, 254–260
  Google Scholar
• 15. Chondrogianni N., Petropoulos I., Grimm S., Georgila K., CatalgolB., Friguet B., Grune T., Gonos, E.S.: Protein damage, repairand proteolysis. Mol. Aspects Med., 2014; 35: 1–71
  Google Scholar
• 16. Circu M.L., Aw T.Y.: Reactive oxygen species, cellular redoxsystems, and apoptosis. Free Radic. Biol. Med., 2010; 48: 749–762
  Google Scholar
• 17. Citta A., Folda A., Scutari G., Cesaro L., Bindoli A., Rigobello,M.P.: Inhibition of thiore8doxin reductase by lanthanum chloride.J. Inorg. Biochem., 2012; 117: 18–24
  Google Scholar
• 18. Collet J.F., Messens J.: Structure, function, and mechanism ofthioredoxin proteins. Antioxid. Redox Signal., 2010; 13: 1205–1216
  Google Scholar
• 19. Cortes-Bratti X., Bassères E., Herrera-Rodriguez F., Botero-Kleiven S., Coppotelli G., Andersen J.B., Masucci M.G., HolmgrenA., Chaves-Olarte E., Frisan T., Avila-Carino J.: Thioredoxin 80-activated-monocytes (TAMs) inhibit the replication of intracellularpathogens. PLoS One, 2011; 6: e16960
  Google Scholar
• 20. Cutillas N., Yellol G.S., de Haro C., Vicente C., Rodríguez V., RuizJ.: Anticancer cyclometalated complexes of platinum group metalsand gold. Coord. Chem. Rev., 2013; 257: 2784–2791
  Google Scholar
• 21. de Oliveira K.N., Andermark V., Onambele L.A., Dahl G., ProkopA., Ott, I.: Organotin complexes containing carboxylate ligandswith maleimide and naphthalimide derived partial structures: TrxRinhibition, cytotoxicity and activity in resistant cancer cells. Eur.J. Med. Chem., 2014; 87: 794–800
  Google Scholar
• 22. Dmitrenko O., Orlova T., Terenetskaya I.: Medium controlledphotochemistry of provitamin D: From solutions to liquid crystals.J. Mol. Liq., 2018; 267: 428–435
  Google Scholar
• 23. Dobrovolska O., Rychkov G., Shumilina E., Nerinovski K.,Schmidt A., Shabalin K., Yakimov A., Dikiy A.: Structural insightsinto interaction between mammalian methionine sulfoxide reductaseB1 and thioredoxin. J. Biomed. Biotechnol., 2012; 2012: 586539
  Google Scholar
• 24. Dóka É., Pader I., Bíró A., Johansson K., Cheng Q., Ballagó K.,Prigge J.R., Pastor-Flores D., Dick T.P., Schmidt E.E., Arnér E.S., NagyP.: A novel persulfide detection method reveals protein persulfideandpolysulfide-reducing functions of thioredoxin and glutathionesystems. Sci. Adv., 2016; 2: e1500968
  Google Scholar
• 25. Ellgaard L. Ruddock L.W.: The human protein disulphideisomerase family: Substrate interactions and functional properties.EMBO Rep., 2005; 6: 28–32
  Google Scholar
• 26. Fang J., Holmgren A.: Inhibition of thioredoxin and thioredoxinreductase by 4-hydroxy-2-nonenal in vitro and in vivo. J.Am. Chem. Soc., 2006; 128: 1879–1885
  Google Scholar
• 27. Fujiwara N., Fujii T., Fujii J., Taniguchi N.: Roles of N-terminalactive cysteines and C-terminal cysteine-selenocysteine in thecatalytic mechanism of mammalian thioredoxin reductase. J. Biochem.,2001; 129: 803–812
  Google Scholar
• 28. Galligan J.J., Petersen D.R.: The human protein disulfideisomerase gene family. Hum. Genomics, 2012; 6: 6
  Google Scholar
• 29. Gandin V., Fernandes A.P.: Metal-and semimetal-containing inhibitorsof thioredoxin reductase as anticancer agents. Molecules,2015; 20: 12732–12756
  Google Scholar
• 30. Gaschler M.M., Stockwell B.R.: Lipid peroxidation in cell death.Biochem. Biophys. Res. Commun., 2017; 482: 419–425
  Google Scholar
• 31. Ghezzi P.: Protein glutathionylation in health and disease.Biochim. Biophys. Acta, 2013; 1830: 3165–3172
  Google Scholar
• 32. Gil-Bea F., Akterin S., Persson T., Mateos L., Sandebring A.,Avila-Cariño J., Gutierrez-Rodriguez A., Sundström E., HolmgrenA., Winblad B., Cedazo-Minguez A.: Thioredoxin-80 is a product ofalpha-secretase cleavage that inhibits amyloid-beta aggregationand is decreased in Alzheimer’s disease brain. EMBO Mol. Med.,2012; 4: 1097–1111
  Google Scholar
• 33. Goroncy A.K., Koshiba S., Tochio N., Tomizawa T., Inoue M.,Tanaka A., Sugano S., Kigawa T., Yokoyama S.: Solution structureof the C-terminal DUF1000 domain of the human thioredoxin-like 1 protein. Proteins, 2010; 78: 2176–2180
  Google Scholar
• 34. Gromer S., Urig S., Becker K.: The thioredoxin system – fromscience to clinic. Med. Res. Rev., 2004; 24: 40–89
  Google Scholar
• 35. Hashemy S.I., Ungerstedt J.S., Avval F.Z., Holmgren A.: Motexafingadolinium, a tumor-selective drug targeting thioredoxinreductase and ribonucleotide reductase. J. Biol. Chem., 2006; 281:10691–10697
  Google Scholar
• 36. Hatahet F., Ruddock L.W.: Protein disulfide isomerase: A criticalevaluation of its function in disulfide bond formation. Antioxid.Redox Signal., 2009; 11: 2807–2850
  Google Scholar
• 37. Hickey J.L., Ruhayel R.A., Barnard P.J., Baker M.V., Berners-PriceS.J., Filipovska A.: Mitochondria-targeted chemotherapeutics: Therational design of gold (I) N-heterocyclic carbene complexes thatare selectively toxic to cancer cells and target protein selenolsin preference to thiols. J. Am. Chem. Soc., 2008; 130: 12570–12571
  Google Scholar
• 38. Holmgren A., Lu J.: Thioredoxin and thioredoxin reductase:Current research with special reference to human disease. Biochem.Biophys. Res. Commun., 2010; 396: 120–124
  Google Scholar
• 39. Hruza L.L., Pentland A.P.: Mechanisms of UV–induced inflammation.J. Invest. Dermatol., 1993; 100: S35–S41
  Google Scholar
• 40. Ishii T., Funato Y., Miki H.: Thioredoxin-related protein 32(TRP32) specifically reduces oxidized phosphatase of regeneratingliver (PRL). J. Biol. Chem., 2013; 288: 7263–7270
  Google Scholar
• 41. Jiménez A., Zu W., Rawe V.Y., Pelto-Huikko M., Flickinger C.J.,Sutovsky P., Gustafsson J.Å. Oko R., Miranda-Vizuete A.: Spermatocyte/spermatid-specific thioredoxin-3, a novel Golgi apparatusassociatedthioredoxin, is a specific marker of aberrant spermatogenesis.J. Biol. Chem., 2004; 279: 34971–34982
  Google Scholar
• 42. Jones D.A.: Rosacea, reactive oxygen species, and azelaic acid.J. Clin. Aesthet. Dermatol., 2009; 2: 26–30
  Google Scholar
• 43. Ju Y., Wu L., Yang G.: Thioredoxin 1 regulation of protein Sdesulfhydration.Biochem. Biophys. Rep., 2016; 5: 27–34
  Google Scholar
• 44. Kakkar P., Singh B.K.: Mitochondria: A hub of redox activitiesand cellular distress control. Mol. Cell. Biochem., 2007; 305: 235–253
  Google Scholar
• 45. Karlenius T.C., Tonissen, K.F.: Thioredoxin and cancer:A rolefor thioredoxin in all states of tumor oxygenation. Cancers, 2010;2: 209–232
  Google Scholar
• 46. Korkina L.: Metabolic and redox barriers in the skin exposedto drugs and xenobiotics. Expert Opin. Drug Metab. Toxicol., 2016;12: 377–388
  Google Scholar
• 47. Lee S., Kim S.M., Lee R.T.: Thioredoxin and thioredoxin targetproteins: From molecular mechanisms to functional significance.Antioxid. Redox Signal., 2013; 18: 1165–1207
  Google Scholar
• 48. Lehmann B., Meurer M.: Vitamin D metabolism. Dermatol.Ther., 2010; 23, 2–12
  Google Scholar
• 49. Li G.Z., Liang H.F., Liao B., Zhang L., Ni Y.A., Zhou H.H., ZhangE.L., Zhang B.X., Chen X.P.: PX-12 inhibits the growth of hepatocelluarcarcinoma by inducing S-phase arrest, ROS-dependent apoptosisand enhances 5-FU cytotoxicity. Am. J. Transl. Res., 2015;7: 1528–1540
  Google Scholar
• 50. Li H., Xu C., Li Q., Gao X., Sugano E., Tomita H., Yang L., Shi S.:Thioredoxin 2 offers protection against mitochondrial oxidativestress in H9c2 cells and against myocardial hypertrophy inducedby hyperglycemia. Int. J. Mol. Sci., 2017; 18: 1958
  Google Scholar
• 51. Liao J., Wang K., Yao W., Yi X., Yan H., Chen M., Lan X.: Cloning,expression and antioxidant activity of a thioredoxin peroxidasefrom Branchiostoma belcheri tsingtaunese. PLoS One, 2017;12: e0175162
  Google Scholar
• 52. Lillig C.H., Holmgren A.: Thioredoxin and related molecules –from biology to health and disease. Antioxid. Redox Signal., 2007;9: 25–47
  Google Scholar
• 53. Lu J., Papp L.V., Fang J., Rodriguez-Nieto S., Zhivotovsky B.,Holmgren A.: Inhibition of mammalian thioredoxin reductase bysome flavonoids: Implications for myricetin and quercetin anticanceractivity. Cancer Res., 2006; 66: 4410–4418
  Google Scholar
• 54. Lu Y., Wang X., Liu Z., Jin B., Chu D., Zhai H., Zhang F., Li K.,Ren G., Miranda-Vizuete A., Guo X., Fan D.: Identification and distributionof thioredoxin-like 2 as the antigen for the monoclonalantibody MC3 specific to colorectal cancer. Proteomics, 2008; 8:2220–2229
  Google Scholar
• 55. Maillet A., Pervaiz S.: Redox regulation of p53, redox effectorsregulated by p53: A subtle balance. Antioxid. Redox Signal.,2012; 16: 1285–1294
  Google Scholar
• 56. Maulik N., Das D.K.: Emerging potential of thioredoxin andthioredoxin interacting proteins in various disease conditions.Biochim. Biophys. Acta, 2008; 1780: 1368–1382
  Google Scholar
• 57. Mukherjee A., Martin S.G.: The thioredoxin system: A key targetin tumour and endothelial cells. Br. J. Radiol., 2008; 81: S57–S68
  Google Scholar
• 58. Mura P., Camalli M., Bindoli A., Sorrentino F., Casini A., GabbianiC., Corsini M., Zanello P., Rigobello M.P., Messori L.: Activity ofrat cytosolic thioredoxin reductase is strongly decreased by trans-[bis (2-amino-5-methylthiazole) tetrachlororuthenate (III)]: Firstreport of relevant thioredoxin reductase inhibition for a rutheniumcompound. J. Med. Chem., 2007; 50: 5871–5874
  Google Scholar
• 59. Ng H.L., Chen S., Chew E.H., Chui W.K.: Applying the designedmultiple ligands approach to inhibit dihydrofolate reductase andthioredoxin reductase for anti-proliferative activity. Eur. J. Med.Chem., 2016; 115: 63–74
  Google Scholar
• 60. Oehninger L., Küster L.N., Schmidt C., Muñoz-Castro A., ProkopA., Ott I.: A chemical-biological evaluation of rhodium (I) N-heterocycliccarbene complexes as prospective anticancer drugs. Chem.Eur. J., 2013; 19: 17871–17880
  Google Scholar
• 61. Oguro A., Imaoka S.: Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport. Sci. Rep., 2019; 9: 15296
  Google Scholar
• 62. Oka O.B., Bulleid N.J.: Forming disulfides in the endoplasmicreticulum. Biochim. Biophys. Acta, 2013; 1833: 2425–2429
  Google Scholar
• 63. Orlova T.N., Terenetskaya I.P.: Possible use of provitamin D3photoisomerization for spectral dosimetry of bioactive antirachiticUV radiation. J. Appl. Spectrosc., 2009; 76, 240–244
  Google Scholar
• 64. Ortego L., Cardoso F., Martins S., Fillat M.F., Laguna A., MeirelesM., Villacampa M.D., Gimeno M.C.: Strong inhibition of thioredoxinreductase by highly cytotoxic gold (I) complexes. DNA bindingstudies. J. Inorg. Biochem., 2014; 130: 32–37
  Google Scholar
• 65. Palanisamy R., Bhatt P., Kumaresan V., Chaurasia M.K., GnanamA.J., Pasupuleti M., Kasi M., Arockiaraj J.: A redox active site containing murrel cytosolic thioredoxin: Analysis of immunologicalproperties. Fish Shellfish Immunol., 2014; 36: 141–150
  Google Scholar
• 66. Poet G.J., Oka O.B., van Lith M., Cao Z., Robinson P.J., PringleM.A., Arnér E.S., Bulleid N.J.: Cytosolic thioredoxin reductase 1 isrequired for correct disulfide formation in the ER. EMBO J., 2017;36: 693–702
  Google Scholar
• 67. Powis G., Wipf P., Lynch S.M., Birmingham A., Kirkpatrick D.L.:Molecular pharmacology and antitumor activity of palmarumycin-based inhibitors of thioredoxin reductase. Mol. Cancer Ther.,2006; 5: 630–636
  Google Scholar
• 68. Prast-Nielsen S., Huang H.H., Williams, D.L.: Thioredoxin glutathionereductase: Its role in redox biology and potential as a targetfor drugs against neglected diseases. Biochim. Biophys. Acta,2011; 1810: 1262–1271
  Google Scholar
• 69. Ramanathan R.K., Stephenson J.J., Weiss G.J., Pestano L.A., LoweA., Hiscox A., Leos R.A., Martin J.C., Kirkpatrick L., Richards D.A.:A phase I trial of PX-12, a small-molecule inhibitor of thioredoxin-1, administered as a 72-hour infusion every 21 days in patientswith advanced cancers refractory to standard therapy. Invest. NewDrugs, 2012; 30: 1591–1596
  Google Scholar
• 70. Raninga P.V., Di Trapani G., Vuckovic S., Bhatia M., TonissenK.F.: Inhibition of thioredoxin 1 leads to apoptosis in drug-resistantmultiple myeloma. Oncotarget, 2015; 6: 15410–15424
  Google Scholar
• 71. Ren X., Zou L., Lu J., Holmgren A.: Selenocysteine in mammalianthioredoxin reductase and application of ebselen as a therapeutic.Free Radic. Biol. Med., 2018; 127: 238–247
  Google Scholar
• 72. Ren X., Zou L., Zhang X., Branco V., Wang J., Carvalho C., HolmgrenA., Lu J.: Redox signaling mediated by thioredoxin and glutathionesystems in the central nervous system. Antioxid. RedoxSignal., 2017; 27: 989–1010
  Google Scholar
• 73. Rendón J.L., Miranda-Leyva M., Guevara-Flores A., Martínez-González J.J., Del Arenal I.P., Flores-Herrera O., Pardo J.P.: Insightinto the mechanistic basis of the hysteretic-like kinetic behaviorof thioredoxin-glutathione reductase (TGR). Enzyme Res., 2018;2018: 3215462
  Google Scholar
• 74. Rhee S.G.: Overview on peroxiredoxin. Mol. Cells, 2016; 39: 1–5
  Google Scholar
• 75. Rhee S.G., Woo H.A., Kil I.S., Bae S.H.: Peroxiredoxin functionsas a peroxidase and a regulator and sensor of local peroxides. J.Biol. Chem., 2012; 287: 4403–4410
  Google Scholar
• 76. Rodriguez-Garcia A., Hevia D., Mayo J.C., Gonzalez-MenendezP., Coppo L., Lu J., Holmgren A., Sainz R.M.: Thioredoxin 1 modulatesapoptosis induced by bioactive compounds in prostate cancercells. Redox Biol., 2017; 12: 634–647
  Google Scholar
• 77. Roos G., Foloppe N., Van Laer K., Wyns L., Nilsson L., GeerlingsP., Messens J.: How thioredoxin dissociates its mixed disulfide. PLoSComput. Biol., 2009; 5: e1000461
  Google Scholar
• 78. Saccoccia, F., Angelucci F., Boumis G., Carotti D., Desiato G.,Miele A.E., Bellelli A.: Thioredoxin reductase and its inhibitors.Curr. Protein Pept. Sci., 2014; 15, 621–646
  Google Scholar
• 79. Sandargo B., Thongbai B., Praditya D., Steinmann E., StadlerM., Surup F.: Antiviral 4-hydroxypleurogrisein and antimicrobialpleurotin derivatives from cultures of the nematophagous basidiomyceteHohenbuehelia grisea. Molecules, 2018; 23: 2697
  Google Scholar
• 80. Sugiura Y., Araki K., Iemura S.I., Natsume T., Hoseki J., Nagata,K.: Novel thioredoxin-related transmembrane protein TMX4 hasreductase activity. J. Biol. Chem., 2010; 285: 7135–7142
  Google Scholar
• 81. Sweeney M., Coyle R., Kavanagh P., Berezin A.A., Re D.L., ZissimouG.A., Koutentis P.A., Carty M.P., Aldabbagh F.: Discovery ofanti-cancer activity for benzo [1,2,4] triazin-7-ones: Very strongcorrelation to pleurotin and thioredoxin reductase inhibition.Bioorg. Med. Chem., 2016; 24: 3565–3570
  Google Scholar
• 82. Tan S.X., Greetham D., Raeth S., Grant C.M., Dawes I.W., PerroneG.G.: The thioredoxin-thioredoxin reductase system can functionin vivo as an alternative system to reduce oxidized glutathionein Saccharomyces cerevisiae. J. Biol. Chem., 2010; 285: 6118–6126
  Google Scholar
• 83. Toledano M.B., Delaunay-Moisan A., Outten C.E., Igbaria A.:Functions and cellular compartmentation of the thioredoxin andglutathione pathways in yeast. Antioxid. Redox Signal., 2013; 18:1699–1711
  Google Scholar
• 84. Tonissen K.F., Di Trapani G.: Thioredoxin system inhibitors asmediators of apoptosis for cancer therapy. Mol. Nutr. Food Res.,2009; 53: 87–103
  Google Scholar
• 85. Ukuwela A.A., Bush A.I., Wedd A.G., Xiao Z.: Glutaredoxinsemploy parallel monothiol-dithiol mechanisms to catalyze thioldisulfideexchanges with protein disulfides. Chem. Sci., 2018; 9:1173–1183
  Google Scholar
• 86. Vandervore L.V., Schot R., Milanese C., Smits D.J., Kasteleijn E.,Fry A.E., Pilz D.T., Brock S., Börklü-Yücel E., Post M., Bahi-BuissonN., Sánchez-Soler M.J., van Slegtenhors M., Keren B., Afenjar A.i wsp.: TMX2 is a crucial regulator of cellular redox state, and itsdysfunction causes severe brain developmental abnormalities. Am.J. Hum. Genet, 2019; 105: 1126–1147
  Google Scholar
• 87. Watanabe R., Nakamura H., Masutani H., Yodoi J.: Anti-oxidative,anti-cancer and anti-inflammatory actions by thioredoxin 1 and thioredoxin-binding protein-2. Pharmacol. Ther., 2010; 127:261–270
  Google Scholar
• 88. Wu C., Parrott A.M., Fu C., Liu T., Marino S.M., Gladyshev V.N.,Jain M.R., Baykal A.T., Li Q., Oka S., Sadoshima J., Beuve A., SimmonsW.J., Li H.: Thioredoxin 1-mediated post-translational modifications:Reduction, transnitrosylation, denitrosylation, and relatedproteomics methodologies. Antioxid. Redox Signal., 2011;15: 2565–2604
  Google Scholar
• 89. Yoshioka J.: Thioredoxin superfamily and its effects on cardiacphysiology and pathology. Compr. Physiol., 2011; 5: 513–530
  Google Scholar
• 90. Zeng H.H., Wang L.H.: Targeting thioredoxin reductase: Anticanceragents and chemopreventive compounds. Med. Chem.,2010; 6: 286–297
  Google Scholar
• 91. Zhang J., Zhang B., Li X., Han X., Liu R., Fang J.: Small moleculeinhibitors of mammalian thioredoxin reductase as potential anticanceragents: An update. Med. Res. Rev., 2019; 39: 5–39
  Google Scholar
• 92. Zhang J.J., Muenzner J.K., Abu El Maaty M.A., Karge B., SchobertR., Wölfl S., Ott I.: A multi-target caffeine derived rhodium (I) Nheterocycliccarbene complex: Evaluation of the mechanism ofaction. Dalton Trans., 2016; 45: 13161–13168
  Google Scholar
• 93. Zhu H., Tao X., Zhou L., Sheng B., Zhu X., Zhu X.: Expressionof thioredoxin 1 and peroxiredoxins in squamous cervical carcinomaand its predictive role in NACT. BMC Cancer, 2019; 19: 865
  Google Scholar

Full text