Cellular and Molecular Life Sciences

, Volume 75, Issue 9, pp 1567–1586 | Cite as

The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?

  • Alexey A. Tinkov
  • Geir BjørklundEmail author
  • Anatoly V. Skalny
  • Arne Holmgren
  • Margarita G. Skalnaya
  • Salvatore Chirumbolo
  • Jan Aaseth


Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell’s major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Genetic and environmental factors like selenium status influence the activity of TrxR. Research shows that the Trx/TrxR system plays a significant role in the physiology of the adipose tissue, in carbohydrate metabolism, insulin production and sensitivity, blood pressure regulation, inflammation, chemotactic activity of macrophages, and atherogenesis. Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported.


Selenium Thioredoxin reductase Diabetes Obesity Thioredoxin interacting protein 



Human immunodeficiency virus


Nicotinamide adenine dinucleotide phosphate


Peroxisome-proliferator-activated receptor-gamma






Thioredoxin reductase


Thioredoxin reductase



This paper was financially supported by the Ministry of Education and Science of the Russian Federation on the program to improve the competitiveness of Peoples’ Friendship University of Russia (RUDN University) among the world’s leading research and education centers in 2016–2020.


  1. 1.
    Zhang J, Svehlíková V, Bao Y, Howie AF, Beckett GJ, Williamson G (2003) Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional and translational modulation. Carcinogenesis 24:497–503PubMedCrossRefGoogle Scholar
  2. 2.
    Campbell L, Howie F, Arthur JR, Nicol F, Beckett G (2007) Selenium and sulforaphane modify the expression of selenoenzymes in the human endothelial cell line EAhy926 and protect cells from oxidative damage. Nutrition 23:138–144 (Erratum in: Nutrition; 23:378) PubMedCrossRefGoogle Scholar
  3. 3.
    Wataha JC, Lewis JB, McCloud VV, Shaw M, Omata Y, Lockwood PE, Messer RL, Hansen JM (2008) Effect of mercury(II) on Nrf2, thioredoxin reductase-1 and thioredoxin-1 in human monocytes. Dent Mater 24:765–772PubMedCrossRefGoogle Scholar
  4. 4.
    Crane MS, Howie AF, Arthur JR, Nicol F, Crosley LK, Beckett GJ (2009) Modulation of thioredoxin reductase-2 expression in EAhy926 cells: implications for endothelial selenoprotein hierarchy. Biochim Biophys Acta 1790:1191–1197PubMedCrossRefGoogle Scholar
  5. 5.
    Erkhembayar S, Mollbrink A, Eriksson M, Larsen EH, Eriksson LC (2011) Selenium homeostasis and induction of thioredoxin reductase during long term selenite supplementation in the rat. J Trace Elem Med Biol 25:254–259PubMedCrossRefGoogle Scholar
  6. 6.
    Barrera LN, Cassidy A, Wang W, Wei T, Belshaw NJ, Johnson IT, Brigelius-Flohé R, Bao Y (2012) TrxR1 and GPx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death. Biochim Biophys Acta 1823:1914–1924PubMedCrossRefGoogle Scholar
  7. 7.
    Yan J, Zheng Y, Min Z, Ning Q, Lu S (2013) Selenium effect on selenoprotein transcriptome in chondrocytes. Biometals 26:285–296PubMedCrossRefGoogle Scholar
  8. 8.
    Liu H, Xu H, Huang K (2017) Selenium in the prevention of atherosclerosis and its underlying mechanisms. Metallomics 9(1):21–37PubMedCrossRefGoogle Scholar
  9. 9.
    Nagarajan N, Oka S, Sadoshima J (2016) Modulation of signaling mechanisms in the heart by thioredoxin 1. Free Radic Biol Med. PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Lu J, Holmgren A (2014) The thioredoxin antioxidant system. Free Radic Biol Med 66:75–87PubMedCrossRefGoogle Scholar
  11. 11.
    D’Annunzio V, Perez V, Boveris A, Gelpi RJ, Poderoso JJ (2016) Role of thioredoxin-1 in ischemic preconditioning, postconditioning and aged ischemic hearts. Pharmacol Res 109:24–31PubMedCrossRefGoogle Scholar
  12. 12.
    Du C, Wu M, Liu H, Ren Y, Du Y, Wu H, Wei J, Liu C, Yao F, Wang H, Zhu Y, Duan H, Shi Y (2016) Thioredoxin-interacting protein regulates lipid metabolism via Akt/mTOR pathway in diabetic kidney disease. Int J Biochem Cell Biol 79:1–13PubMedCrossRefGoogle Scholar
  13. 13.
    Gromer S, Arscott LD, Williams CH Jr, Schirmer RH, Becker K (1998) Human placenta thioredoxin reductase. Isolation of the selenoenzyme, steady state kinetics, and inhibition by therapeutic gold compounds. J Biol Chem 273:20096–20101PubMedCrossRefGoogle Scholar
  14. 14.
    Powers HJ, Hill MH, Mushtaq S, Dainty JR, Majsak-Newman G, Williams EA (2011) Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM). Am J Clin Nutr 93:1274–1284PubMedCrossRefGoogle Scholar
  15. 15.
    Naghashpour M, Amani R, Nutr R, Nematpour S, Haghighizadeh MH (2011) Riboflavin status and its association with serum hs-CRP levels among clinical nurses with depression. J Am Coll Nutr 30:340–347PubMedCrossRefGoogle Scholar
  16. 16.
    Yang J, Hamid S, Liu Q, Cai J, Xu S, Zhang Z (2017) Gene expression of selenoproteins can be regulated by thioredoxin(Txn) silence in chicken cardiomyocytes. J Inorg Biochem 177:118–126PubMedCrossRefGoogle Scholar
  17. 17.
    Sunde RA, Raines AM, Barnes KM, Evenson JK (2009) Selenium status highly regulates selenoprotein mRNA levels for only a subset of the selenoproteins in the selenoproteome. Biosci Rep 29:329–338PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Rundlöf AK, Arnér ES (2004) Regulation of the mammalian selenoprotein thioredoxin reductase 1 in relation to cellular phenotype, growth, and signaling events. Antioxid Redox Signal 6:41–52PubMedCrossRefGoogle Scholar
  19. 19.
    Steinbrenner H, Speckmann B, Klotz LO (2016) Selenoproteins: antioxidant selenoenzymes and beyond. Arch Biochem Biophys 595:113–119PubMedCrossRefGoogle Scholar
  20. 20.
    Zhang X, Zhang L, Zhu JH, Cheng WH (2016) Nuclear selenoproteins and genome maintenance. IUBMB Life 68:5–12PubMedCrossRefGoogle Scholar
  21. 21.
    Eklund H, Gleason FK, Holmgren A (1991) Structural and functional relations among thioredoxins of different species. Proteins 11:13–28PubMedCrossRefGoogle Scholar
  22. 22.
    Holmgren A (1995) Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide. Structure 3(3):239–243PubMedCrossRefGoogle Scholar
  23. 23.
    Montano SJ, Lu J, Gustafsson TN, Holmgren A (2014) Activity assays of mammalian thioredoxin and thioredoxin reductase: fluorescent disulfide substrates, mechanisms, and use with tissue samples. Anal Biochem 449:139–146PubMedCrossRefGoogle Scholar
  24. 24.
    Laurent TC, Moore EC, Reichard P (1964) Enzymatic synthesis of deoxyribonucletides IV Isolation and characterization of thioredoxn, the hydrogen donor from Escherichia coli B. J Biol Chem 239:3436–3444PubMedGoogle Scholar
  25. 25.
    Holmgren A (1985) Thioredoxin. Annu Rev Biochem 54:237–271PubMedCrossRefGoogle Scholar
  26. 26.
    Martin JL (1995) Thioredoxin–a fold for all reasons. Structure 3(3):245–250PubMedCrossRefGoogle Scholar
  27. 27.
    Lillig CH, Holmgren A (2007) Thioredoxin and related molecules-from biology to health and disease. Antioxid Redox Signal 9:25–47PubMedCrossRefGoogle Scholar
  28. 28.
    Arnér ES, Holmgren A (2000) Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 267(20):6102–6109PubMedCrossRefGoogle Scholar
  29. 29.
    Rhee SG, Kil IS (2017) Multiple functions and regulation of mammalian peroxiredoxins. Annu Rev Biochem 86:749–775PubMedCrossRefGoogle Scholar
  30. 30.
    Kallis GB, Holmgren A (1980) Differential reactivity of the functional sulfhydryl groups of cysteine-32 and cysteine-35 present in the reduced form of thioredoxin from Escherichia coli. J Biol Chem 255(21):10261–10265PubMedGoogle Scholar
  31. 31.
    Bertini R, Howard OM, Dong HF, Oppenheim JJ, Bizzarri C, Sergi R, Caselli G, Pagliei S, Romines B, Wilshire JA, Mengozzi M, Nakamura H, Yodoi J, Pekkari K, Gurunath R, Holmgren A, Herzenberg LA, Herzenberg LA, Ghezzi P (1999) Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells. J Exp Med 189(11):1783–1789PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Pekkari K, Gurunath R, Arner ES, Holmgren A (2000) Truncated thioredoxin is a mitogenic cytokine for resting human peripheral blood mononuclear cells and is present in human plasma. J Biol Chem 275(48):37474–37480PubMedCrossRefGoogle Scholar
  33. 33.
    Gil-Bea F, Akterin S, Persson T, Mateos L, Sandebring A, Avila-Cariño J, Gutierrez-Rodriguez A, Sundström E, Holmgren A, Winblad B, Cedazo-Minguez A (2012) Thioredoxin-80 is a product of alpha-secretase cleavage that inhibits amyloid-beta aggregation and is decreased in Alzheimer’s disease brain. EMBO Mol Med 4(10):1097–1111PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Couchie D, Vaisman B, Abderrazak A, Mahmood DFD, Hamza MM, Canesi F, Diderot V, El Hadri K, Nègre-Salvayre A, Le Page A, Fulop T, Remaley AT, Rouis M (2017) Human plasma thioredoxin-80 increases with age and in ApoE(−/−) mice induces inflammation, angiogenesis, and atherosclerosis. Circulation 136(5):464–475PubMedCrossRefGoogle Scholar
  35. 35.
    Fritz-Wolf K, Kehr S, Stumpf M, Rahlfs S, Becker K (2011) Crystal structure of the human thioredoxin reductase-thioredoxin complex. Nat Commun 2:383PubMedCrossRefGoogle Scholar
  36. 36.
    Park BJ, Cha MK, Kim IH (2014) Thioredoxin 1 as a serum marker for ovarian cancer and its use in combination with CA125 for improving the sensitivity of ovarian cancer diagnoses. Biomarkers 19(7):604–610PubMedCrossRefGoogle Scholar
  37. 37.
    Chong CR, Chan WPA, Nguyen TH, Liu S, Procter NE, Ngo DT et al (2014) Thioredoxin-interacting protein: pathophysiology and emerging pharmacotherapeutics in cardiovascular disease and diabetes. Cardiovasc Drugs Ther 28(4):347–360PubMedCrossRefGoogle Scholar
  38. 38.
    Nakamura H, De Rosa SC, Yodoi J, Holmgren A, Ghezzi P, Herzenberg LA (2001) Chronic elevation of plasma thioredoxin: inhibition of chemotaxis and curtailment of life expectancy in AIDS. Proc Natl Acad Sci USA 98:2688–2693PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Hofer S, Rosenhagen C, Nakamura H, Yodoi J, Bopp C, Zimmermann JB, Goebel M, Schemmer P, Hoffmann K, Schulze-Osthoff K, Breitkreutz R, Weigand MA (2009) Thioredoxin in human and experimental sepsis. Crit Care Med 37:2155–2159PubMedCrossRefGoogle Scholar
  40. 40.
    Nakamura H, Hoshino Y, Okuyama H, Matsuo Y, Yodoi J (2009) Thioredoxin 1 delivery as new therapeutics. Adv Drug Deliv Rev 61:303–309PubMedCrossRefGoogle Scholar
  41. 41.
    Matsuo Y, Yodoi J (2013) Extracellular thioredoxin: a therapeutic tool to combat inflammation. Cytokine Growth Factor Rev 24:345–353PubMedCrossRefGoogle Scholar
  42. 42.
    Lincoln DT, Ali Emadi EM, Tonissen KF, Clarke FM (2003) The thioredoxin-thioredoxin reductase system: over-expression in human cancer. Anticancer Res 23(3B):2425–2433PubMedGoogle Scholar
  43. 43.
    Powis G, Mustacich D, Coon A (2000) The role of the redox protein thioredoxin in cell growth and cancer. Free Radic Biol Med 29(3–4):312–322PubMedCrossRefGoogle Scholar
  44. 44.
    Arnér ES, Holmgren A (2006) The thioredoxin system in cancer. Semin Cancer Biol 16(6):419PubMedCrossRefGoogle Scholar
  45. 45.
    Vance TM, Azabdaftari G, Pop EA, Lee SG, Su LJ, Fontham ET, Bensen JT, Steck SE, Arab L, Mohler JL, Chen MH, Koo SI, Chun OK (2015) Thioredoxin 1 in prostate tissue is associated with gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidants. Prostate Cancer 2015(2015):728046PubMedPubMedCentralGoogle Scholar
  46. 46.
    O’Connell K, Ohlendieck K (2009) Proteomic DIGE analysis of the mitochondria-enriched fraction from aged rat skeletal muscle. Proteomics 9:5509–5524PubMedCrossRefGoogle Scholar
  47. 47.
    Catani MV, Savini I, Duranti G, Caporossi D, Ceci R, Sabatini S, Avigliano L (2004) Nuclear factor kappaB and activating protein 1 are involved in differentiation-related resistance to oxidative stress in skeletal muscle cells. Free Radic Biol Med 37:1024–1036PubMedCrossRefGoogle Scholar
  48. 48.
    Picard M, Jung B, Liang F, Azuelos I, Hussain S, Goldberg P, Godin R, Danialou G, Chaturvedi R, Rygiel K, Matecki S, Jaber S, Des Rosiers C, Karpati G, Ferri L, Burelle Y, Turnbull DM, Taivassalo T, Petrof BJ (2012) Mitochondrial dysfunction and lipid accumulation in the human diaphragm during mechanical ventilation. Am J Respir Crit Care Med 186:1140–1149PubMedCrossRefGoogle Scholar
  49. 49.
    Conrad M, Jakupoglu C, Moreno SG, Lippl S, Banjac A, Schneider M, Beck H, Hatzopoulos AK, Just U, Sinowatz F, Schmahl W, Chien KR, Wurst W, Bornkamm GW, Brielmeier M (2004) Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function. Mol Cell Biol 24:9414–9423PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Matsushima S, Ide T, Yamato M, Matsusaka H, Hattori F, Ikeuchi M, Kubota T, Sunagawa K, Hasegawa Y, Kurihara T, Oikawa S, Kinugawa S, Tsutsui H (2006) Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice. Circulation 113:1779–1786PubMedCrossRefGoogle Scholar
  51. 51.
    Tsutsui H, Kinugawa S, Matsushima S (2008) Oxidative stress and mitochondrial DNA damage in heart failure. Circ J 72(Suppl A):A31–A37PubMedCrossRefGoogle Scholar
  52. 52.
    Tsutsui H, Kinugawa S, Matsushima S (2009) Mitochondrial oxidative stress and dysfunction in myocardial remodelling. Cardiovasc Res 81:449–456PubMedCrossRefGoogle Scholar
  53. 53.
    Kumar V, Kitaeff N, Hampton MB, Cannell MB, Winterbourn CC (2009) Reversible oxidation of mitochondrial peroxiredoxin 3 in mouse heart subjected to ischemia and reperfusion. FEBS Lett 583:997–1000PubMedCrossRefGoogle Scholar
  54. 54.
    Lijnen PJ, Piccart Y, Coenen T, Prihadi JS (2012) Angiotensin II-induced mitochondrial reactive oxygen species and peroxiredoxin-3 expression in cardiac fibroblasts. J Hypertens 30:1986–1991PubMedCrossRefGoogle Scholar
  55. 55.
    Murphy MP (2012) Mitochondrial thiols in antioxidant protection and redox signaling: distinct roles for glutathionylation and other thiol modifications. Antioxid Redox Signal 16:476–495PubMedCrossRefGoogle Scholar
  56. 56.
    Mowbray AL, Kang DH, Rhee SG, Kang SW, Jo H (2008) Laminar shear stress up-regulates peroxiredoxins (PRX) in endothelial cells: PRX 1 as a mechanosensitive antioxidant. J Biol Chem 283:1622–1627PubMedCrossRefGoogle Scholar
  57. 57.
    Lowes DA, Galley HF (2010) Mitochondrial protection by the thioredoxin-2 and GSH systems in an in vitro endothelial model of sepsis. Biochem J 436:123–132CrossRefGoogle Scholar
  58. 58.
    Munro D, Treberg JR (2017) A radical shift in perspective: mitochondria as regulators of reactive oxygen species. J Exp Biol 220(Pt 7):1170–1180PubMedCrossRefGoogle Scholar
  59. 59.
    Munro D, Banh S, Sotiri E, Tamanna N, Treberg JR (2016) The thioredoxin and glutathione-dependent H2O2 consumption pathways in muscle mitochondria: involvement in H2O2 metabolism and consequence to H2O2 efflux assays. Free Radic Biol Med 96:334–346PubMedCrossRefGoogle Scholar
  60. 60.
    Lothrop AP, Snider GW, Ruggles EL, Patel AS, Lees WJ, Hondal RJ (2014) Selenium as an electron acceptor during the catalytic mechanism of thioredoxin reductase. Biochemistry 53(4):654–663PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Sandalova T, Zhong L, Lindqvist Y, Holmgren A, Schneider G (2001) Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. Proc Natl Acad Sci USA 98:9533–9538PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Cheng Q, Sandalova T, Lindqvist Y, Arnér ES (2009) Crystal structure and catalysis of the selenoprotein thioredoxin reductase 1. J Biol Chem 284:3998–4008PubMedCrossRefGoogle Scholar
  63. 63.
    Lu J, Chew EH, Holmgren A (2007) Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc Natl Acad Sci USA 104:12288–12293PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Bragadin M, Scutari G, Folda A, Bindoli A, Rigobello MP (2004) Effect of metal complexes on thioredoxin reductase and the regulation of mitochondrial permeability conditions. Ann N Y Acad Sci 1030:348–354PubMedCrossRefGoogle Scholar
  65. 65.
    El-Sharaky AS, Newairy AA, Badreldeen MM, Eweda SM, Sheweita SA (2007) Protective role of selenium against renal toxicity induced by cadmium in rats. Toxicology. 235:185–193 (Erratum in: Toxicology. 2007;242:160) PubMedCrossRefGoogle Scholar
  66. 66.
    Carvalho CM, Chew EH, Hashemy SI, Lu J, Holmgren A (2008) Inhibition of the human thioredoxin system. A molecular mechanism of mercury toxicity. J Biol Chem 283:11913–11923PubMedCrossRefGoogle Scholar
  67. 67.
    Branco V, Canário J, Holmgren A, Carvalho C (2011) Inhibition of the thioredoxin system in the brain and liver of zebra-seabreams exposed to waterborne methylmercury. Toxicol Appl Pharmacol 251:95–103. PubMedCrossRefGoogle Scholar
  68. 68.
    Carvalho CM, Lu J, Zhang X, Arnér ES, Holmgren A (2011) Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: implications for treatment of mercury poisoning. FASEB J 25:370–381. PubMedCrossRefGoogle Scholar
  69. 69.
    Branco V, Canário J, Lu J, Holmgren A, Carvalho C (2012) Mercury and selenium interaction in vivo: effects on thioredoxin reductase and glutathione peroxidase. Free Radic Biol Med 52:781–793PubMedCrossRefGoogle Scholar
  70. 70.
    Branco V, Ramos P, Canário J, Lu J, Holmgren A, Carvalho C (2012) Biomarkers of adverse response to mercury: histopathology versus thioredoxin reductase activity. J Biomed Biotechnol 2012:359879. PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Saccoccia E, Angelucci F, Boumis G, Carotti D, Desiato G, Miele AE, Bellelli A (2014) Thioredoxin reductase and its inhibitors. Curr Protein Pept Sci 15:621–646PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Venardos K, Harrison G, Headrick J, Perkins A (2004) Effects of dietary selenium on glutathione peroxidase and thioredoxin reductase activity and recovery from cardiac ischemia–reperfusion. J Trace Elem Med Biol 18(1):81–88PubMedCrossRefGoogle Scholar
  73. 73.
    Mahmood DF, Abderrazak A, El Hadri K, Simmet T, Rouis M (2013) The thioredoxin system as a therapeutic target in human health and disease. Antioxid Redox Signal 19(11):1266–1303PubMedCrossRefGoogle Scholar
  74. 74.
    World CJ, Yamawaki H, Berk BC (2006) Thioredoxin in the cardiovascular system. J Mol Med (Berl). 84(12):997–1003PubMedCrossRefGoogle Scholar
  75. 75.
    Ebrahimian T, Touyz RM (2008) Thioredoxin in vascular biology: role in hypertension. Antioxid Redox Signal 10(6):1127–1136PubMedCrossRefGoogle Scholar
  76. 76.
    Crunkhorn S (2017) Cardiovascular disease: thioredoxin lowers hypertension. Nat Rev Drug Discov 16(4):240PubMedGoogle Scholar
  77. 77.
    Eren E, Aykal G, Sayrac S, Erol O, Ellidag HY, Yilmaz N (2017) Relationship between thioredoxin and thioredoxin-binding protein in patients with gestational diabetes mellitus. J Matern Fetal Neonatal Med 30(2):164–168PubMedCrossRefGoogle Scholar
  78. 78.
    Nakatsukasa Y, Tsukahara H, Tabuchi K, Tabuchi M, Magami T, Yamada M, Fujii Y, Yashiro M, Tsuge M, Morishima T (2013) Thioredoxin-1 and oxidative stress status in pregnant women at early third trimester of pregnancy: relation to maternal and neonatal characteristics. J Clin Biochem Nutr 52(1):27–31PubMedCrossRefGoogle Scholar
  79. 79.
    Yu L, Fan C, Li Z, Zhang J, Xue X, Xu Y, Zhao G, Yang Y, Wang H (2017) Melatonin rescues cardiac thioredoxin system during ischemia–reperfusion injury in acute hyperglycemic state by restoring Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner. J Pineal Res. CrossRefPubMedGoogle Scholar
  80. 80.
    Karunasinghe N, Han DY, Zhu S, Duan H, Ko YJ, Yu JF, Triggs CM, Ferguson LR (2013) Effects of supplementation with selenium, as selenized yeast, in a healthy male population from New Zealand. Nutr Cancer 65:355–366PubMedCrossRefGoogle Scholar
  81. 81.
    Grundy SM (2005) Metabolic syndrome scientific statement by the American Heart Association and the National Heart, Lung, and Blood Institute. Atherosclerosis Thromb Vasc Physiol 25(11):2243–2244CrossRefGoogle Scholar
  82. 82.
    Bricker LA, Greydanus DE (2008) The metabolic syndrome: a gathering challenge in a time of abundance. Adolesc Med State Art Rev 19(3):475–497PubMedGoogle Scholar
  83. 83.
    Dietrich P, Hellerbrand C (2014) Non-alcoholic fatty liver disease, obesity and the metabolic syndrome. Best Pract Res Clin Gastroenterol 28(4):637–653PubMedCrossRefGoogle Scholar
  84. 84.
    Kaimul AM, Nakamura H, Masutani H, Yodoi J (2007) Thioredoxin and thioredoxin-binding protein-2 in cancer and metabolic syndrome. Free Radic Biol Med 43(6):861–868PubMedCrossRefGoogle Scholar
  85. 85.
    Peña-Orihuela P, Camargo A, Rangel-Zuñiga OA, Perez-Martinez P, Cruz-Teno C, Delgado-Lista J, Roche HM (2013) Antioxidant system response is modified by dietary fat in adipose tissue of metabolic syndrome patients. J Nutr Biochem 24(10):1717–1723PubMedCrossRefGoogle Scholar
  86. 86.
    Palmieri VO, Coppola B, Grattagliano I, Casieri V, Cardinale G, Portincasa P et al (2013) Oxidized LDL receptor 1 gene polymorphism in patients with metabolic syndrome. Eur J Clin Investig 43(1):41–48CrossRefGoogle Scholar
  87. 87.
    Jankovic A, Korac A, Buzadzic B, Otasevic V, Stancic A, Daiber A, Korac B (2015) Redox implications in adipose tissue (dys) function—a new look at old acquaintances. Redox Biol 6:19–32PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Jankovic A, Korac A, Srdic-Galic B, Buzadzic B, Otasevic V, Stancic A, Korac B (2014) Differences in the redox status of human visceral and subcutaneous adipose tissues—relationships to obesity and metabolic risk. Metabolism 63(5):661–671PubMedCrossRefGoogle Scholar
  89. 89.
    Zhou C, Routh VH (2017) Thioredoxin-1 overexpression in the ventromedial nucleus of the hypothalamus (VMH) preserves the counterregulatory response to hypoglycemia during type 1 diabetes mellitus in male rats. Diabetes. CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Yang J, Hamid S, Cai J, Liu Q, Xu S, Zhang Z (2017) Selenium deficiency-induced thioredoxin suppression and thioredoxin knock down disbalanced insulin responsiveness in chicken cardiomyocytes through PI3K/Akt pathway inhibition. Cell Signal 38:192–200PubMedCrossRefGoogle Scholar
  91. 91.
    Steinbrenner H (2013) Interference of selenium and selenoproteins with the insulin-regulated carbohydrate and lipid metabolism. Free Radic Biol Med 65:1538–1547PubMedCrossRefGoogle Scholar
  92. 92.
    Peng X, Giménez-Cassina A, Petrus P, Conrad M, Rydén M, Arnér ES (2016) Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness. Sci Rep 6:28080. PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Claessens M, Saris WH, Bouwman FG, Evelo CT, Hul GB, Blaak EE, Mariman EC (2007) Differential valine metabolism in adipose tissue of low and high fat-oxidizing obese subjects. Proteom Clin Appl 1(10):1306–1315CrossRefGoogle Scholar
  94. 94.
    Heinonen S, Buzkova J, Muniandy M, Kaksonen R, Ollikainen M, Ismail K, Hakkarainen A, Lundbom J, Lundbom N, Vuolteenaho K, Moilanen E, Kaprio J, Rissanen A, Suomalainen A, Pietiläinen KH (2015) Impaired mitochondrial biogenesis in adipose tissue in acquired obesity. Diabetes 64(9):3135–3145PubMedCrossRefGoogle Scholar
  95. 95.
    Yin X, Sun C, Cui Y (2006) Study of different expressed proteins between white adipose tissue of patients with type 2 diabetes mellitus and controls [J]. Shandong Med J 7:002Google Scholar
  96. 96.
    Lejnev K, Khomsky L, Bokvist K, Mistriel-Zerbib S, Naveh T, Farb TB, Alsina-Fernandez J, Atlas D (2016) Thioredoxin-mimetic peptides (TXM) inhibit inflammatory pathways associated with high-glucose and oxidative stress. Free Radic Biol Med 99:557–571PubMedCrossRefGoogle Scholar
  97. 97.
    Anca PL, Bogdana V, Olivia T, Horia V, Dumitru O, Leon Z (2014) P70—the relations between immunity, oxidative stress and inflammation markers, in childhood obesity. Free Radic Biol Med 75:S44–S45CrossRefGoogle Scholar
  98. 98.
    Kursawe R, Caprio S, Giannini C, Narayan D, Lin A, D’Adamo E, Shulman GI (2013) Decreased transcription of ChREBP-α/β isoforms in abdominal subcutaneous adipose tissue of obese adolescents with prediabetes or early type 2 diabetes associations with insulin resistance and hyperglycemia. Diabetes 62(3):837–844PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Jiménez-Osorio AS, González-Reyes S, García-Niño WR, Moreno-Macías H, Rodríguez-Arellano ME, Vargas-Alarcón G, Zúñiga J, Barquera R, Pedraza-Chaverri J (2016) Association of nuclear factor-erythroid 2-related factor 2, thioredoxin interacting protein, and heme oxygenase-1 gene polymorphisms with diabetes and obesity in mexican patients. Oxid Med Cell Longev 2016:7367641PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Bouwman FG, Claessens M, van Baak MA, Noben JP, Wang P, Saris WH, Mariman EC (2009) The physiologic effects of caloric restriction are reflected in the in vivo adipocyte-enriched proteome of overweight/obese subjects. J Proteome Res 8(12):5532–5540PubMedCrossRefGoogle Scholar
  101. 101.
    Huh JY, Kim Y, Jeong J, Park J, Kim I, Huh KH, Kim YS, Woo HA, Rhee SG, Lee KJ, Ha H (2012) Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression. Antioxid Redox Signal 16:229–243PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Roca-Rivada A, Alonso J, Al-Massadi O, Castelao C, Peinado JR, Seoane LM et al (2011) Secretome analysis of rat adipose tissues shows location-specific roles for each depot type. J Proteom 74(7):1068–1079CrossRefGoogle Scholar
  103. 103.
    Chiellini C, Cochet O, Negroni L, Samson M, Poggi M, Ailhaud G et al (2008) Characterization of human mesenchymal stem cell secretome at early steps of adipocyte and osteoblast differentiation. BMC Mol Biol 9(1):1CrossRefGoogle Scholar
  104. 104.
    Adachi J, Kumar C, Zhang Y, Mann M (2007) In-depth analysis of the adipocyte proteome by mass spectrometry and bioinformatics. Mol Cell Proteom 6(7):1257–1273CrossRefGoogle Scholar
  105. 105.
    Vanella L, Li M, Rezzani R, Rodella L, Martasek P, Peterson SJ, Abraham NG (2010) Perturbations in redox homeostasis in visceral fat due to decreases in HO-1, adiponectin and pAMPK adversely effects vascular function in obese mice. Circulation 122(Suppl 21):A19686Google Scholar
  106. 106.
    Rojanathammanee L, Rakoczy S, Kopchick J, Brown-Borg HM (2014) Effects of insulin-like growth factor 1 on glutathione S-transferases and thioredoxin in growth hormone receptor knockout mice. Age (Dordrecht) 36(4):9687CrossRefGoogle Scholar
  107. 107.
    Xing SQ, Zhang CG, Yuan JF, Yang HM, Zhao SD, Zhang H (2015) Adiponectin induces apoptosis in hepatocellular carcinoma through differential modulation of thioredoxin proteins. Biochem Pharmacol 93(2):221–231PubMedCrossRefGoogle Scholar
  108. 108.
    Liu JS, Xu JY, Huang J, Zhao Y, Ye F, Zhong LW (2016) A reciprocal inhibitory relationship between adiponectin and mammalian cytosolic thioredoxin. Sci Bull 61(19):1513–1521CrossRefGoogle Scholar
  109. 109.
    Rindler PM, Plafker SM, Szweda LI, Kinter M (2013) High dietary fat selectively increases catalase expression within cardiac mitochondria. J Biol Chem 288(3):1979–1990PubMedCrossRefGoogle Scholar
  110. 110.
    Zagrodzki PAWEŁ, Joniec A, Gawlik MAŁGORZATA, Gawlik M, Krosniak M, Folta M, Zachwieja ZOFIA (2007) High fructose model of oxidative stress and metabolic disturbances in rats. Part I. Antioxidant status of rats’ tissues. Bull Vet Inst Pulawy 51(3):407Google Scholar
  111. 111.
    Fisher-Wellman KH, Mattox TA, Thayne K, Katunga LA, La Favor JD, Neufer PD, Hickner RC, Wingard CJ, Anderson EJ (2013) Novel role for thioredoxin reductase-2 in mitochondrial redox adaptations to obesogenic diet and exercise in heart and skeletal muscle. J Physiol 591(14):3471–3486PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Qin H, Zhang X, Ye F, Zhong L (2014) High-fat diet-induced changes in liver thioredoxin and thioredoxin reductase as a novel feature of insulin resistance. FEBS Open Bio 31(4):928–935CrossRefGoogle Scholar
  113. 113.
    Salmon A, Flores LC, Li Y, Van Remmen H, Richardson A, Ikeno Y (2012) Reduction of glucose intolerance with high fat feeding is associated with anti-inflammatory effects of thioredoxin 1 overexpression in mice. Pathobiol Aging Age Relat Dis 2:17101CrossRefGoogle Scholar
  114. 114.
    Patwari P, Higgins LJ, Chutkow WA, Yoshioka J, Lee RT (2006) The interaction of thioredoxin with Txnip evidence for formation of a mixed disulfide by disulfide exchange. J Biol Chem 281(31):21884–21891PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Chutkow WA, Lee RT (2011) Thioredoxin regulates adipogenesis through thioredoxin-interacting protein (Txnip) protein stability. J Biol Chem 286(33):29139–29145PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Chutkow WA, Birkenfeld AL, Brown JD, Lee HY, Frederick DW, Yoshioka J, Shulman GI (2010) Deletion of the α-arrestin protein Txnip in mice promotes adiposity and adipogenesis while preserving insulin sensitivity. Diabetes 59(6):1424–1434PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Koenen TB, Stienstra R, Van Tits LJ, De Graaf J, Stalenhoef AF, Joosten LA, Netea MG (2011) Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1β transcription in human adipose tissue. Diabetes 60(2):517–524PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Giordano A, Murano I, Mondini E, Perugini J, Smorlesi A, Severi I et al (2013) Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. J Lipid Res 54(9):2423–2436PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Rajalin AM, Micoogullari M, Sies H, Steinbrenner H (2014) Upregulation of the thioredoxin-dependent redox system during differentiation of 3T3-L1 cells to adipocytes. Biol Chem 395(6):667–677PubMedCrossRefGoogle Scholar
  120. 120.
    Song JS, Cho HH, Lee BJ, Bae YC, Jung JS (2010) Role of thioredoxin 1 and thioredoxin 2 on proliferation of human adipose tissue-derived mesenchymal stem cells. Stem Cells Dev 20(9):1529–1537CrossRefGoogle Scholar
  121. 121.
    Karasawa H, Takaishi K, Kumagae Y (2011) Obesity-induced diabetes in mouse strains treated with gold thioglucose: a novel animal model for studying β-cell dysfunction. Obesity (Silver Spring) 19(3):514–521CrossRefGoogle Scholar
  122. 122.
    Zhao Y, Li X, Tang S (2015) Retrospective analysis of the relationship between elevated plasma levels of TXNIP and carotid intima-media thickness in subjects with impaired glucose tolerance and early type 2 diabetes mellitus. Diabetes Res Clin Pract 109(2):372–377PubMedCrossRefGoogle Scholar
  123. 123.
    Blouet C, Liu SM, Jo YH, Chua S, Schwartz GJ (2012) TXNIP in Agrp neurons regulates adiposity, energy expenditure, and central leptin sensitivity. J Neurosci 32(29):9870–9877PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Pitts MW, Reeves MA, Hashimoto AC, Ogawa A, Kremer P, Seale LA, Berry MJ (2013) Deletion of selenoprotein M leads to obesity without cognitive deficits. J Biol Chem 288(36):26121–26134PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Liang Y, Lin SL, Wang CW, Yao HD, Zhang ZW, Xu SW (2014) Effect of selenium on selenoprotein expression in the adipose tissue of chickens. Biol Trace Elem Res 160(1):41–48PubMedCrossRefGoogle Scholar
  126. 126.
    Pinto A, Juniper DT, Sanil M, Morgan L, Clark L, Sies H et al (2012) Supranutritional selenium induces alterations in molecular targets related to energy metabolism in skeletal muscle and visceral adipose tissue of pigs. J Inorg Biochem 114:47–54PubMedCrossRefGoogle Scholar
  127. 127.
    Kim CH, Younossi ZM (2008) Nonalcoholic fatty liver disease: a manifestation of the metabolic syndrome. Clevel Clin J Med 75(10):721–728CrossRefGoogle Scholar
  128. 128.
    Okuyama H, Son A, Ahsan M, Masutani H, Nakamura H, Yodoi J (2008) Thioredoxin and thioredoxin binding protein 2 in the liver. IUBMB Life 60(10):656–660PubMedCrossRefGoogle Scholar
  129. 129.
    Okanoue T, Yamauchi N, Furutani M, Hirohama A, Sumida Y, Nakashima T (2005) Predictors of nonalcoholic steatohepatitis in Japanese patients: thioredoxin and NASH. In: Okita K (ed) NASH and nutritional therapy. Springer, Tokyo, pp 64–72CrossRefGoogle Scholar
  130. 130.
    Sumida Y, Nakashima T, Yoh T, Furutani M, Hirohama A, Kakisaka Y, Kashima K (2003) Serum thioredoxin levels as a predictor of steatohepatitis in patients with nonalcoholic fatty liver disease. J Hepatol 38(1):32–38PubMedCrossRefGoogle Scholar
  131. 131.
    Nakashima T, Sumida Y, Furutani M, Hirohama A, Okita M, Mitsuyoshi H, Okanoue T (2005) Elevation of serum thioredoxin levels in patients with nonalcoholic steatohepatitis. Hepatol Res 33(2):135–137PubMedGoogle Scholar
  132. 132.
    Mitsuyoshi H, Itoh Y, Okanoue T (2006) Role of oxidative stress in non-alcoholic steatohepatitis. Nihon rinsho Jpn J Clin Med 64(6):1077–1082Google Scholar
  133. 133.
    Tanaka N, Sano K, Horiuchi A, Tanaka E, Kiyosawa K, Aoyama T (2008) Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol 42(4):413–418PubMedCrossRefGoogle Scholar
  134. 134.
    Gornicka A, Morris-Stiff G, Thapaliya S, Papouchado BG, Berk M, Feldstein AE (2011) Transcriptional profile of genes involved in oxidative stress and antioxidant defense in a dietary murine model of steatohepatitis. Antioxid Redox Signal 15(2):437–445PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Grattagliano I, Caraceni P, Calamita G, Ferri D, Gargano I, Palasciano G, Portincasa P (2008) Severe liver steatosis correlates with nitrosative and oxidative stress in rats. Eur J Clin Investig 38(7):523–530CrossRefGoogle Scholar
  136. 136.
    Shao W, Yu Z, Chiang Y, Yang Y, Chai T, Foltz W et al (2012) Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS One 7(1):e28784PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Xiao J, Liu Y, Xing F, Leung TM, Liong EC, Tipoe GL (2016) Bee’s honey attenuates non-alcoholic steatohepatitis-induced hepatic injury through the regulation of thioredoxin-interacting protein—NLRP3 inflammasome pathway. Eur J Nutr 55:1–13CrossRefGoogle Scholar
  138. 138.
    Donnelly KL, Margosian MR, Sheth SS, Lusis AJ, Parks EJ (2004) Increased lipogenesis and fatty acid reesterification contribute to hepatic triacylglycerol stores in hyperlipidemic Txnip−/− mice. J Nutri 134(6):1475–1480CrossRefGoogle Scholar
  139. 139.
    Haque JA, McMahan RS, Campbell JS, Shimizu-Albergine M, Wilson AM, Botta D et al (2010) Attenuated progression of diet-induced steatohepatitis in glutathione-deficient mice. Lab Investig 90(12):1704–1717PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Shearn CT, Mercer KE, Orlicky DJ, Hennings L, Smathers-McCullough RL, Stiles BL et al (2014) Short term feeding of a high fat diet exerts an additive effect on hepatocellular damage and steatosis in liver-specific PTEN knockout mice. PLoS One 9(5):e96553PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Duan XY, Zhao HP, Fan JG (2010) Dynamic expression of hepatic thioredoxin mRNA in rats with non-alcoholic fatty liver disease. J Dig Dis 11(2):94–100PubMedCrossRefGoogle Scholar
  142. 142.
    Meakin PJ, Chowdhry S, Sharma RS, Ashford FB, Walsh SV, McCrimmon RJ, Ashford ML (2014) Susceptibility of Nrf2-null mice to steatohepatitis and cirrhosis upon consumption of a high-fat diet is associated with oxidative stress, perturbation of the unfolded protein response, and disturbance in the expression of metabolic enzymes but not with insulin resistance. Mol Cell Biol 34(17):3305–3320PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Lu H, Cui W, Klaassen CD (2011) Nrf2 protects against 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative injury and steatohepatitis. Toxicol Appl Pharmacol 256(2):122–135PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Kakisaka Y, Nakashima T, Sumida Y, Yoh T, Nakamura H, Yodoi J, Senmaru H (2002) Elevation of serum thioredoxin levels in patients with type 2 diabetes. Horm Metab Res 34:160–164PubMedCrossRefGoogle Scholar
  145. 145.
    Miyamoto S, Kawano H, Hokamaki J, Soejima H, Kojima S, Kudoh T, Nakamura H (2005) Increased plasma levels of thioredoxin in patients with glucose intolerance. Intern Med 44(11):1127–1132PubMedCrossRefGoogle Scholar
  146. 146.
    Ikegami H, Ono M, Fujisawa T, Hiromine Y, Kawabata Y, Yamato E (2008) Molecular scanning of the gene for thioredoxin, an antioxidative and antiapoptotic protein, and genetic susceptibility to type 1 diabetes. Ann N Y Acad Sci 1150(1):103–105PubMedCrossRefGoogle Scholar
  147. 147.
    Calabrese V, Mancuso C, Sapienza M, Puleo E, Calafato S, Cornelius C, Castellino P (2007) Oxidative stress and cellular stress response in diabetic nephropathy. Cell Stress Chaperones 12(4):299–306PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Calabrese V, Cornelius C, Leso V, Trovato-Salinaro A, Ventimiglia B, Cavallaro M, Castellino P (2012) Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes. Biochim Biophys Acta (BBA) Mol Basis Dis 1822(5):729–736CrossRefGoogle Scholar
  149. 149.
    Aaseth J, Stoa-Birketvedt G (2000) Glutathione in overweight patients with poorly controlled type 2 diabetes. J Trace Elem Exp Med 13(1):105–111CrossRefGoogle Scholar
  150. 150.
    Hamada Y, Fujii H, Kitazawa R, Yodoi J, Kitazawa S, Fukagawa M (2009) Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic osteopenia: a novel role of oxidative stress and therapeutic implications. Bone 44(5):936–941PubMedCrossRefGoogle Scholar
  151. 151.
    Hotta M, Tashiro F, Ikegami H, Niwa H, Ogihara T, Yodoi J, Miyazaki JI (1998) Pancreatic β cell-specific expression of thioredoxin, an antioxidative and antiapoptotic protein, prevents autoimmune and streptozotocin-induced diabetes. J Exp Med 188(8):1445–1451PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Yamamoto M, Yamato E, Shu-Ichi T, Tashiro F, Ikegami H, Yodoi J, Miyazaki JI (2007) Transgenic expression of antioxidant protein thioredoxin in pancreatic β cells prevents progression of type 2 diabetes mellitus. Antioxid Redox Signal 10(1):43–50CrossRefGoogle Scholar
  153. 153.
    Chernatynskaya AV, Looney B, Hu H, Zhu X, Xia CQ (2011) Administration of recombinant human thioredoxin-1 significantly delays and prevents autoimmune diabetes in nonobese diabetic mice through modulation of autoimmunity. Diabetes Metab Res Rev 27(8):809–812PubMedCrossRefGoogle Scholar
  154. 154.
    Muoio DM (2007) TXNIP links redox circuitry to glucose control. Cell Metab 5(6):412–414PubMedCrossRefGoogle Scholar
  155. 155.
    Li X, Rong Y, Zhang M, Wang XL, LeMaire SA, Coselli JS, Shen YH (2009) Up-regulation of thioredoxin interacting protein (Txnip) by p38 MAPK and FOXO1 contributes to the impaired thioredoxin activity and increased ROS in glucose-treated endothelial cells. Biochem Biophys Res Commun 381(4):660–665PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Lappalainen Z, Lappalainen J, Oksala NK, Laaksonen DE, Khanna S, Sen CK, Atalay M (2009) Diabetes impairs exercise training-associated thioredoxin response and glutathione status in rat brain. J Appl Physiol 106(2):461–467PubMedCrossRefGoogle Scholar
  157. 157.
    Shaked M, Ketzinel-Gilad M, Ariav Y, Cerasi E, Kaiser N, Leibowitz G (2009) Insulin counteracts glucotoxic effects by suppressing thioredoxin-interacting protein production in INS-1E beta cells and in Psammomys obesus pancreatic islets. Diabetologia 52(4):636–644PubMedCrossRefGoogle Scholar
  158. 158.
    Robinson KA, Brock JW, Buse MG (2013) Posttranslational regulation of thioredoxin-interacting protein. J Mol Endocrinol 50(1):59–71PubMedCrossRefGoogle Scholar
  159. 159.
    Parikh H, Carlsson E, Chutkow WA, Johansson LE, Storgaard H, Poulsen P et al (2007) TXNIP regulates peripheral glucose metabolism in humans. PLoS Med 4(5):e158PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Chen J, Hui ST, Couto FM, Mungrue IN, Davis DB, Attie AD, Shalev A (2008) Thioredoxin-interacting protein deficiency induces Akt/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes. FASEB J 22(10):3581–3594PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Masson E, Koren S, Razik F, Goldberg H, Kwan EP, Sheu L et al (2009) High β-cell mass prevents streptozotocin-induced diabetes in thioredoxin-interacting protein-deficient mice. Am J Physiol Endocrinol Metab 296(6):E1251–E1261PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Xu G, Chen J, Jing G, Shalev A (2013) Thioredoxin-interacting protein regulates insulin transcription through microRNA-204. Nat Med 19(9):1141–1146PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Guzmán AM, Arredondo Olguín M, Olivares Gronhert M (2015) Glycemic control and oxidative stress markers and their relationship with the thioredoxin interacting protein (TXNIP) gene in type 2 diabetic patients. Nutr Hosp 31(3):1129–1133Google Scholar
  164. 164.
    Wei J, Shi Y, Hou Y, Ren Y, Du C, Zhang L, Duan H (2013) Knockdown of thioredoxin-interacting protein ameliorates high glucose-induced epithelial to mesenchymal transition in renal tubular epithelial cells. Cell Signal 25(12):2788–2796PubMedCrossRefGoogle Scholar
  165. 165.
    Lillig CH, Holmgren A (2007) Thioredoxin and related molecules—from biology to health and disease. Antioxid Redox Signal 9(1):25–47PubMedCrossRefGoogle Scholar
  166. 166.
    Ghezzi P (2013) Protein glutathionylation in health and disease. Biochim Biophys Acta 1830(5):3165–3172PubMedCrossRefGoogle Scholar
  167. 167.
    Zhang H, Forman HJ (2012) Glutathione synthesis and its role in redox signaling. Semin Cell Dev Biol 23(7):722–728PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Benhar M, Forrester MT, Stamler JS (2009) Protein denitrosylation: enzymatic mechanisms and cellular functions. Nat Rev Mol Cell Biol 10(10):721–732PubMedCrossRefGoogle Scholar
  169. 169.
    Corbett JA (2008) Thioredoxin-interacting protein is killing my β-cells! Diabetes 57(4):797–798PubMedCrossRefGoogle Scholar
  170. 170.
    Tang L, Zhang Y, Jiang Y, Willard L, Ortiz E, Wark L et al (2011) Dietary wolfberry ameliorates retinal structure abnormalities in db/db mice at the early stage of diabetes. Exp Biol Med 236(9):1051–1063CrossRefGoogle Scholar
  171. 171.
    Shelton MD, Kern TS, Mieyal JJ (2007) Glutaredoxin regulates nuclear factor κ-B and intercellular adhesion molecule in müller cells model of diabetic retinopathy. J Biol Chem 282(17):12467–12474PubMedCrossRefGoogle Scholar
  172. 172.
    Hou X, Song J, Li XN, Zhang L, Wang X, Chen L, Shen YH (2010) Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK–FOXO3 pathway. Biochem Biophys Res Commun 396(2):199–205PubMedCrossRefGoogle Scholar
  173. 173.
    Liu JH, Liu DF, Wang NN, Lin HL, Mei X (2011) Possible role for the thioredoxin system in the protective effects of probucol in the pancreatic islets of diabetic rats. Clin Exp Pharmacol Physiol 38(8):528–533PubMedCrossRefGoogle Scholar
  174. 174.
    Thirunavukkarasu M, Penumathsa SV, Koneru S, Juhasz B, Zhan L, Otani H, Maulik N (2007) Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: role of nitric oxide, thioredoxin, and heme oxygenase. Free Radic Biol Med 43(5):720–729PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Packer L, Kraemer K, Rimbach G (2001) Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 17(10):888–895PubMedCrossRefGoogle Scholar
  176. 176.
    Mueller AS, Pallauf J (2006) Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice. J Nutr Biochem 17(8):548–560PubMedCrossRefGoogle Scholar
  177. 177.
    Atalay M, Bilginoglu A, Kokkola T, Oksala N, Turan B (2011) Treatments with sodium selenate or doxycycline offset diabetes-induced perturbations of thioredoxin-1 levels and antioxidant capacity. Mol Cell Biochem 351(1–2):125–131PubMedCrossRefGoogle Scholar
  178. 178.
    Navas-Acien A, Silbergeld EK, Streeter RA, Clark JM, Burke TA, Guallar E (2006) Arsenic exposure and type 2 diabetes: a systematic review of the experimental and epidemiologic evidence. Environ Health Perspect 114:641–648PubMedCrossRefGoogle Scholar
  179. 179.
    Tseng CH (2004) The potential biological mechanisms of arsenic-induced diabetes mellitus. Toxicol Appl Pharmacol 197(2):67–83PubMedCrossRefGoogle Scholar
  180. 180.
    Sun HJ, Rathinasabapathi B, Wu B, Luo J, Pu LP, Ma LQ (2014) Arsenic and selenium toxicity and their interactive effects in humans. Environ Int 69:148–158PubMedCrossRefGoogle Scholar
  181. 181.
    Tatsunami R, Oba T, Takahashi K, Tampo Y (2009) Methylglyoxal causes dysfunction of thioredoxin and thioredoxin reductase in endothelial cells. J Pharmacol Sci 111(4):426–432PubMedCrossRefGoogle Scholar
  182. 182.
    Luan R, Liu S, Yin T, Lau WB, Wang Q, Guo W et al (2009) High glucose sensitizes adult cardiomyocytes to ischaemia/reperfusion injury through nitrative thioredoxin inactivation. Cardiovasc Res 83(2):294–302PubMedCrossRefGoogle Scholar
  183. 183.
    Schulze PC, Yoshioka J, Takahashi T, He Z, King GL, Lee RT (2004) Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein. J Biol Chem 279(29):30369–30374PubMedCrossRefGoogle Scholar
  184. 184.
    Li J, Zhu H, Shen E, Wan L, Arnold JMO, Peng T (2010) Deficiency of rac1 blocks NADPH oxidase activation, inhibits endoplasmic reticulum stress, and reduces myocardial remodeling in a mouse model of type 1 diabetes. Diabetes 59(8):2033–2042PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Samuel SM, Thirunavukkarasu M, Penumathsa SV, Koneru S, Zhan L, Maulik G et al (2010) Thioredoxin-1 gene therapy enhances angiogenic signaling and reduces ventricular remodeling in infarcted myocardium of diabetic rats. Circulation 121(10):1244–1255PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    Briones AM, Touyz RM (2010) Oxidative stress and hypertension: current concepts. Curr Hypertens Rep 12(2):135–142PubMedCrossRefGoogle Scholar
  187. 187.
    Maulik N, Das DK (2008) Emerging potential of thioredoxin and thioredoxin interacting proteins in various disease conditions. Biochim Biophys Acta (BBA) Gen Subj 1780(11):1368–1382CrossRefGoogle Scholar
  188. 188.
    Anema SM, Walker SW, Howie AF, Arthur JR, Nicol F, Beckett GJ (1999) Thioredoxin reductase is the major selenoprotein expressed in human umbilical-vein endothelial cells and is regulated by protein kinase C. Biochem J 342(1):111–117PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Wu Q, Huang K, Xu H (2003) Effects of long-term selenium deficiency on glutathione peroxidase and thioredoxin reductase activities and expressions in rat aorta. J Inorg Biochem 94(4):301–306PubMedCrossRefGoogle Scholar
  190. 190.
    Mansego ML, Blesa S, Gonzalez-Albert V, Tormos MC, Saez G, Redon J, Chaves FJ (2007) Discordant response of glutathione and thioredoxin systems in human hypertension? Antioxid Redox Signal 9(4):507–514PubMedCrossRefGoogle Scholar
  191. 191.
    Mansego ML, Solar GDM, Alonso MP, Martínez F, Saez GT, Escudero JCM, Chaves FJ (2011) Polymorphisms of antioxidant enzymes, blood pressure and risk of hypertension. J Hypertens 29(3):492–500PubMedCrossRefGoogle Scholar
  192. 192.
    Ferreira NE, Omae S, Pereira A, Rodrigues MV, Miyakawa AA, Campos LC, Mill JG (2012) Thioredoxin interacting protein genetic variation is associated with diabetes and hypertension in the Brazilian general population. Atherosclerosis 221(1):131–136PubMedCrossRefGoogle Scholar
  193. 193.
    Van Greevenbroek MMJ, Vermeulen VM, Feskens EJM, Evelo CT, Kruijshoop M, Hoebee B, De Bruin TWA (2007) Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus. Diabet Med 24(5):498–504PubMedCrossRefGoogle Scholar
  194. 194.
    Tanito M, Nakamura H, Kwon YW, Teratani A, Masutani H, Shioji K, Yodoi J (2004) Enhanced oxidative stress and impaired thioredoxin expression in spontaneously hypertensive rats. Antioxid Redox Signal 6(1):89–97PubMedCrossRefGoogle Scholar
  195. 195.
    Widder JD, Fraccarollo D, Galuppo P, Hansen JM, Jones DP, Ertl G, Bauersachs J (2009) Attenuation of angiotensin II-induced vascular dysfunction and hypertension by overexpression of thioredoxin 2. Hypertension 54(2):338–344PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Zhang H, Luo Y, Zhang W, He Y, Dai S, Zhang R et al (2007) Endothelial-specific expression of mitochondrial thioredoxin improves endothelial cell function and reduces atherosclerotic lesions. Am J Pathol 170(3):1108–1120PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Fukai T (2009) Mitochondrial thioredoxin novel regulator for NADPH oxidase and angiotensin II-induced hypertension. Hypertension 54(2):224–225PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Ebrahimian T, He Y, Schiffrin EL, Touyz RM (2007) Differential regulation of thioredoxin and NAD (P) H oxidase by angiotensin II in male and female mice. J Hypertens 25(6):1263–1271PubMedCrossRefGoogle Scholar
  199. 199.
    Choi H, Tostes RC, Webb RC (2011) Thioredoxin reductase inhibition reduces relaxation by increasing oxidative stress and s-nitrosylation in mouse aorta. J Cardiovasc Pharmacol 58(5):522PubMedPubMedCentralCrossRefGoogle Scholar
  200. 200.
    Choi H, Allahdadi KJ, Tostes RC, Webb RC (2011) Augmented S-nitrosylation contributes to impaired relaxation in angiotensin II hypertensive mouse aorta: role of thioredoxin reductase. J Hypertens 29(12):2359PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Xu S, He Y, Vokurkova M, Touyz RM (2009) Endothelial cells negatively modulate reactive oxygen species generation in vascular smooth muscle cells role of thioredoxin. Hypertension 54(2):427–433PubMedCrossRefGoogle Scholar
  202. 202.
    Trigona WL, Mullarky IK, Cao Y, Sordillo LM (2006) Thioredoxin reductase regulates the induction of haem oxygenase-1 expression in aortic endothelial cells. Biochem J 394(1):207–216PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Koneru S, Penumathsa SV, Thirunavukkarasu M, Zhan L, Maulik N (2009) Thioredoxin-1 gene delivery induces heme oxygenase-1 mediated myocardial preservation after chronic infarction in hypertensive rats. Am J Hypertens 22(2):183–190PubMedCrossRefGoogle Scholar
  204. 204.
    Park YS, Fujiwara N, Koh YH, Miyamoto Y, Suzuki K, Honke K, Taniguchi N (2002) Induction of thioredoxin reductase gene expression by peroxynitrite in human umbilical vein endothelial cells. Biol Chem 383(3–4):683–691PubMedGoogle Scholar
  205. 205.
    Schulze PC, Liu H, Choe E, Yoshioka J, Shalev A, Bloch KD, Lee RT (2006) Nitric oxide-dependent suppression of thioredoxin-interacting protein expression enhances thioredoxin activity. Arterioscler Thromb Vasc Biol 26(12):2666–2672PubMedCrossRefGoogle Scholar
  206. 206.
    Zhang X, Zheng Y, Fried LE, Du Y, Montano SJ, Sohn A, Lu J (2011) Disruption of the mitochondrial thioredoxin system as a cell death mechanism of cationic triphenylmethanes. Free Radic Biol Med 50(7):811–820PubMedPubMedCentralCrossRefGoogle Scholar
  207. 207.
    Kahlos K, Zhang J, Block ER, Patel JM (2003) Thioredoxin restores nitric oxide-induced inhibition of protein kinase C activity in lung endothelial cells. Mol Cell Biochem 254(1–2):47–54PubMedCrossRefGoogle Scholar
  208. 208.
    Rodrigo R, González J, Paoletto F (2011) The role of oxidative stress in the pathophysiology of hypertension. Hypertens Res 34(4):431–440PubMedCrossRefGoogle Scholar
  209. 209.
    Shioji K, Nakamura H (2003) Thioredoxin and atherosclerosis. Rinsho byori Jpn J Clin Pathol 51(11):1106–1110Google Scholar
  210. 210.
    Alehagen U, Aaseth J (2015) Selenium and coenzyme Q10 interrelationship in cardiovascular diseases—a clinician’s point of view. J Trace Elem Med Biol 31:157–162PubMedCrossRefGoogle Scholar
  211. 211.
    Alehagen U, Aaseth J, Johansson P (2015) Less increase of copeptin and MR-proADM due to intervention with selenium and coenzyme Q10 combined: results from a 4-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Biofactors 41(6):443–452PubMedCrossRefGoogle Scholar
  212. 212.
    Alehagen U, Lindahl TL, Aaseth J, Svensson E, Johansson P (2015) Levels of sP-selectin and hs-CRP decrease with dietary intervention with selenium and coenzyme Q10 combined: a secondary analysis of a randomized clinical trial. PLoS One 10(9):e0137680. PubMedPubMedCentralCrossRefGoogle Scholar
  213. 213.
    Wu Y, Yang L, Zhong L (2010) Decreased serum levels of thioredoxin in patients with coronary artery disease plus hyperhomocysteinemia is strongly associated with the disease severity. Atherosclerosis 212(1):351–355PubMedCrossRefGoogle Scholar
  214. 214.
    Miwa K, Kishimoto C, Nakamura H, Makita T, Ishii K, Okuda N, Sasayama S (2003) Increased oxidative stress with elevated serum thioredoxin level in patients with coronary spastic angina. Clin Cardiol 26(4):177–181PubMedCrossRefGoogle Scholar
  215. 215.
    Madrigal-Matute J, Fernandez-Garcia CE, Blanco-Colio LM, Burillo E, Fortuño A, Martinez-Pinna R, Martin-Ventura JL (2015) Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis. Free Radic Biol Med 86:352–361PubMedCrossRefGoogle Scholar
  216. 216.
    Yunfei W, Yang L, Liangwei Z (2011) 535 serum thioredoxin activity is negatively associated with total homocysteine levels in patients with coronary artery disease. Atheroscler Suppl 12(1):113–114CrossRefGoogle Scholar
  217. 217.
    Miwa K, Kishimoto C, Nakamura H, Makita T, Ishii K, Okuda N, Sasayama S (2005) Serum thioredoxin and. α-tocopherol concentrations in patients with major risk factors. Circ J 69(3):291–294PubMedCrossRefGoogle Scholar
  218. 218.
    Augusti PR, Ruviaro AR, Quatrin A, Somacal S, Conterato GMM, Vicentini JT et al (2012) Imbalance in superoxide dismutase/thioredoxin reductase activities in hypercholesterolemic subjects: relationship with low density lipoprotein oxidation. Lipids Health Dis 11(1):1CrossRefGoogle Scholar
  219. 219.
    Cortes R, Martinez-Hervas S, Ivorra C, De Marco G, Gonzalez-Albert V, Rojo-Martínez G, Chaves FJ (2014) Enhanced reduction in oxidative stress and altered glutathione and thioredoxin system response to unsaturated fatty acid load in familial hypercholesterolemia. Clin Biochem 47(18):291–297PubMedCrossRefGoogle Scholar
  220. 220.
    Okuda M, Inoue N, Azumi H, Seno T, Sumi Y, Hirata KI et al (2001) Expression of glutaredoxin in human coronary arteries its potential role in antioxidant protection against atherosclerosis. Arterioscler Thromb Vasc Biol 21(9):1483–1487PubMedCrossRefGoogle Scholar
  221. 221.
    Takagi Y, Gon Y, Todaka T, Nozaki K, Nishiyama A, Sono H, Yodoi J (1998) Expression of thioredoxin ls enhanced in atherosclerotic plaques and during neointima. Lab Investig 78(8):957PubMedGoogle Scholar
  222. 222.
    Nishihira K, Hatakeyama K, Imamura T, Shibata Y, Itabe H, Nakamura H, Asada Y (2005) Thioredoxin and oxidized lipoprotein are increased in unstable plaque obtained by directional coronary atherectomy (angina pectoris, basic/clinical 5 (IHD), The 69th annual scientific meeting of the Japanese Circulation Society). Circ J 69:323Google Scholar
  223. 223.
    Nishihira K, Yamashita A, Imamura T, Hatakeyama K, Sato Y, Nakamura H, Asada Y (2008) Thioredoxin in coronary culprit lesions: possible relationship to oxidative stress and intraplaque hemorrhage. Atherosclerosis 201(2):360–367PubMedCrossRefGoogle Scholar
  224. 224.
    Hokamaki J, Kawano H, Soejima H, Miyamoto S, Kajiwara I, Kojima S, Yodoi J (2005) Plasma thioredoxin levels in patients with unstable angina. Int J Cardiol 99(2):225–231PubMedCrossRefGoogle Scholar
  225. 225.
    Miyamoto S, Kawano H, Sakamoto T, Soejima H, Kajiwara I, Hokamaki J, Nakamura H (2004) Increased plasma levels of thioredoxin in patients with coronary spastic angina. Antioxid Redox Signal 6(1):75–80PubMedCrossRefGoogle Scholar
  226. 226.
    Miyamoto S, Sakamoto T, Soejima H, Shimomura H, Kajiwara I, Kojima S, Nakamura H (2003) Plasma thioredoxin levels and platelet aggregability in patients with acute myocardial infarction. Am Heart J 146(3):465–471PubMedCrossRefGoogle Scholar
  227. 227.
    Okami N, Kawamata T, Yamamoto G, Okada Y, Hori T, Tachikawa T (2009) Laser microdissection-based analysis of hypoxia- and thioredoxin-related genes in human stable carotid plaques. Cardiovasc Pathol 18(5):294–300PubMedCrossRefGoogle Scholar
  228. 228.
    Kim KS, Park NK, Kim SY, Kim DW, Joo SJ, Cho MC (2011) Expression of lectin like oxidized low density lipoprotein receptor-1 in the spontaneous hypertensive rat with high cholesterol diet. J Korean Soc Hypertens 17(2):57–64CrossRefGoogle Scholar
  229. 229.
    Go YM, Son DJ, Park H, Orr M, Hao L, Takabe W, Jones DP (2014) Disturbed flow enhances inflammatory signaling and atherogenesis by increasing thioredoxin-1 level in endothelial cell nuclei. PLoS One 9(9):e108346PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    Dai G, Vaughn S, Zhang Y, Wang ET, Garcia-Cardena G, Gimbrone MA (2007) Biomechanical forces in atherosclerosis-resistant vascular regions regulate endothelial redox balance via phosphoinositol 3-kinase/Akt-dependent activation of Nrf2. Circ Res 101(7):723–733PubMedCrossRefGoogle Scholar
  231. 231.
    Ungvari Z, Bagi Z, Feher A et al (2010) Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol 299(1):H18–H24PubMedPubMedCentralCrossRefGoogle Scholar
  232. 232.
    Kaga S, Zhan L, Matsumoto M et al (2005) Resveratrol enhances neovascularization in the infarcted rat myocardium through the induction of thioredoxin-1, heme oxygenase-1 and vascular endothelial growthfactor. J Mol Cell Cardiol 39(5):813–822PubMedCrossRefGoogle Scholar
  233. 233.
    Xu D, Li Y, Zhang B, Wang Y, Liu Y, Luo Y, Niu W, Dong M, Liu M, Dong H, Zhao P, Li Z (2016) Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats. Int J Med Sci 13(12):942–954PubMedPubMedCentralCrossRefGoogle Scholar
  234. 234.
    Wang XQ, Nigro P, Fujiwara K, Yan C, Berk BC (2012) Thioredoxin interacting protein promotes endothelial cell inflammation in response to disturbed flow by increasing leukocyte adhesion and repressing Kruppel-like factor 2 novelty and significance. Circ Res 110(4):560–568PubMedPubMedCentralCrossRefGoogle Scholar
  235. 235.
    Byon CH, Han T, Wu J, Hui ST (2015) Txnip ablation reduces vascular smooth muscle cell inflammation and ameliorates atherosclerosis in apolipoprotein E knockout mice. Atherosclerosis 241(2):313–321PubMedPubMedCentralCrossRefGoogle Scholar
  236. 236.
    Shimada K, Murayama T, Yokode M, Kita T, Fujita M, Kishimoto C (2011) Olmesartan, a novel angiotensin II type 1 receptor antagonist, reduces severity of atherosclerosis in apolipoprotein E deficient mice associated with reducing superoxide production. Nutr Metab Cardiovasc Dis 21(9):672–678PubMedCrossRefGoogle Scholar
  237. 237.
    Haendeler J, Hoffmann J, Zeiher AM, Dimmeler S (2004) Antioxidant effects of statins via S-nitrosylation and activation of thioredoxin in endothelial cells a novel vasculoprotective function of statins. Circulation 110(7):856–861PubMedCrossRefGoogle Scholar
  238. 238.
    Somacal S, Figueiredo CG, Quatrin A, Ruviaro AR, Conte L, Augusti PR, Duarte MM (2015) The antiatherogenic effect of bixin in hypercholesterolemic rabbits is associated to the improvement of lipid profile and to its antioxidant and anti-inflammatory effects. Mol Cell Biochem 403(1–2):243–253PubMedCrossRefGoogle Scholar
  239. 239.
    Moore KJ, Tabas I (2011) Macrophages in the pathogenesis of atherosclerosis. Cell 145(3):341–355PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    El Hadri K, Mahmood DFD, Couchie D, Jguirim-Souissi I, Genze F, Diderot V, Rouis M (2012) Thioredoxin-1 promotes anti-inflammatory macrophages of the M2 phenotype and antagonizes atherosclerosis. Arterioscler Thromb Vasc Biol 32(6):1445–1452PubMedCrossRefGoogle Scholar
  241. 241.
    Isakov E, Weisman-Shomer P, Benhar M (2014) Suppression of the pro-inflammatory NLRP3/interleukin-1β pathway in macrophages by the thioredoxin reductase inhibitor auranofin. Biochim Biophys Acta (BBA) Gen Subj 1840(10):3153–3161CrossRefGoogle Scholar
  242. 242.
    Billiet L, Furman C, Larigauderie G, Copin C, Brand K, Fruchart JC, Rouis M (2005) Extracellular human thioredoxin-1 inhibits lipopolysaccharide-induced interleukin-1β expression in human monocyte-derived macrophages. J Biol Chem 280(48):40310–40318PubMedCrossRefGoogle Scholar
  243. 243.
    Go YM, Halvey PJ, Hansen JM, Reed M, Pohl J, Jones DP (2007) Reactive aldehyde modification of thioredoxin-1 activates early steps of inflammation and cell adhesion. Am J Pathol 171(5):1670–1681PubMedPubMedCentralCrossRefGoogle Scholar
  244. 244.
    Szuchman-Sapir A, Etzman M, Tamir S (2012) Human atherosclerotic plaque lipid extract impairs the antioxidant defense capacity of monocytes. Biochem Biophys Res Commun 423(4):884–888PubMedCrossRefGoogle Scholar
  245. 245.
    Liu ZB, Shen X (2009) Thioredoxin reductase 1 upregulates MCP-1 release in human endothelial cells. Biochem Biophys Res Commun 386(4):703–708PubMedCrossRefGoogle Scholar
  246. 246.
    Hägg D, Englund MC, Jernås M, Schmidt C, Wiklund O, Hultén LM, Svensson PA (2006) Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages. Atherosclerosis 185(2):282–289PubMedCrossRefGoogle Scholar
  247. 247.
    Kadl A, Meher AK, Sharma PR, Lee MY, Doran AC, Johnstone SR, Kensler T (2010) Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via Nrf2. Circ Res 107(6):737–746PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Yaroslavl State UniversityYaroslavlRussia
  2. 2.Peoples’ Friendship University of Russia (RUDN University)MoscowRussia
  3. 3.Institute of Cellular and Intracellular SymbiosisRussian Academy of SciencesOrenburgRussia
  4. 4.Council for Nutritional and Environmental MedicineMo i RanaNorway
  5. 5.Trace Element Institute for UNESCOLyonFrance
  6. 6.Orenburg State UniversityOrenburgRussia
  7. 7.Department of Medical Biochemistry and Biophysics (MBB)Karolinska InstituteStockholmSweden
  8. 8.Department of Neurological and Movement SciencesUniversity of VeronaVeronaItaly
  9. 9.Research DepartmentInnlandet Hospital TrustBrumunddalNorway
  10. 10.Inland Norway University of Applied SciencesElverumNorway

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