Txnrd1

Summary

Gene Symbol: Txnrd1
Description: thioredoxin reductase 1
Alias: thioredoxin reductase 1, cytoplasmic, NADPH-dependent thioredoxin reductase, selenoprotein oxidoreductase, thioredoxin reductase TR1
Species: rat
Products:     Txnrd1

Top Publications

  1. Lee S, Kim J, Kwon K, Yoon H, Levine R, Ginsburg A, et al. Molecular cloning and characterization of a mitochondrial selenocysteine-containing thioredoxin reductase from rat liver. J Biol Chem. 1999;274:4722-34 pubmed
  2. Lu J, Zhong L, Lönn M, Burk R, Hill K, Holmgren A. Penultimate selenocysteine residue replaced by cysteine in thioredoxin reductase from selenium-deficient rat liver. FASEB J. 2009;23:2394-402 pubmed publisher
    ..These results show a novel mechanism for decoding the UGA stop codon, inserting cysteine to make a full-length enzyme that may be required for selenium assimilation. ..
  3. Rengby O, Cheng Q, Vahter M, Jornvall H, Arner E. Highly active dimeric and low-activity tetrameric forms of selenium-containing rat thioredoxin reductase 1. Free Radic Biol Med. 2009;46:893-904 pubmed publisher
    ..The tetrameric forms of the protein could represent hitherto unknown regulatory states of the enzyme. ..
  4. Urig S, Lieske J, Fritz Wolf K, Irmler A, Becker K. Truncated mutants of human thioredoxin reductase 1 do not exhibit glutathione reductase activity. FEBS Lett. 2006;580:3595-600 pubmed
    ..Furthermore, we show that GSSG binding at the N-terminal active site of TrxR is electrostatically disfavoured. ..
  5. Sandalova T, Zhong L, Lindqvist Y, Holmgren A, Schneider G. Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. Proc Natl Acad Sci U S A. 2001;98:9533-8 pubmed
    ..Our results suggest that mammalian TrxR evolved from the GR scaffold rather than from its prokaryotic counterpart. This evolutionary switch renders cell growth dependent on selenium. ..
  6. Arner E, Sarioglu H, Lottspeich F, Holmgren A, Bock A. High-level expression in Escherichia coli of selenocysteine-containing rat thioredoxin reductase utilizing gene fusions with engineered bacterial-type SECIS elements and co-expression with the selA, selB and selC genes. J Mol Biol. 1999;292:1003-16 pubmed
    ..These results show that with the strategy utilized here, the capacity of selenoprotein synthesis in E. coli is more than sufficient for making possible the use of the bacteria for production of recombinant selenoproteins. ..
  7. Cheng Q, Sandalova T, Lindqvist Y, Arner E. Crystal structure and catalysis of the selenoprotein thioredoxin reductase 1. J Biol Chem. 2009;284:3998-4008 pubmed publisher
  8. Crosley L, Meplan C, Nicol F, Rundlöf A, Arnér E, Hesketh J, et al. Differential regulation of expression of cytosolic and mitochondrial thioredoxin reductase in rat liver and kidney. Arch Biochem Biophys. 2007;459:178-88 pubmed
  9. Xia L, Nordman T, Olsson J, Damdimopoulos A, Björkhem Bergman L, Nalvarte I, et al. The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress. J Biol Chem. 2003;278:2141-6 pubmed
    ..These data demonstrate that the selenoenzyme thioredoxin reductase is an important selenium-dependent ubiquinone reductase and can explain how selenium and ubiquinone, by a combined action, may protect the cell from oxidative damage. ..

More Information

Publications58

  1. Anestål K, Arner E. Rapid induction of cell death by selenium-compromised thioredoxin reductase 1 but not by the fully active enzyme containing selenocysteine. J Biol Chem. 2003;278:15966-72 pubmed
  2. Su D, Novoselov S, Sun Q, Moustafa M, Zhou Y, Oko R, et al. Mammalian selenoprotein thioredoxin-glutathione reductase. Roles in disulfide bond formation and sperm maturation. J Biol Chem. 2005;280:26491-8 pubmed
    ..Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium in male reproduction. ..
  3. Fang J, Lu J, Holmgren A. Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. J Biol Chem. 2005;280:25284-90 pubmed
    ..Modification of TrxR by curcumin provides a possible mechanistic explanation for its cancer preventive activity, shifting the enzyme from an antioxidant to a prooxidant. ..
  4. Zhong L, Holmgren A. Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. J Biol Chem. 2000;275:18121-8 pubmed
    ..Thus selenium is required for the catalytic activities of TrxR explaining the essential role of this trace element in cell growth. ..
  5. Zhong L, Arner E, Ljung J, Aslund F, Holmgren A. Rat and calf thioredoxin reductase are homologous to glutathione reductase with a carboxyl-terminal elongation containing a conserved catalytically active penultimate selenocysteine residue. J Biol Chem. 1998;273:8581-91 pubmed
    ..This showed that the carboxyl-terminal motif was essential for the catalytic activity of the enzyme. ..
  6. Jakupoglu C, Przemeck G, Schneider M, Moreno S, Mayr N, Hatzopoulos A, et al. Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development. Mol Cell Biol. 2005;25:1980-8 pubmed
    ..To investigate the individual contribution of mitochondrial (Txnrd2) and cytoplasmic (Txnrd1) thioredoxin reductases in vivo, we generated a mouse strain with a conditionally targeted deletion of Txnrd1...
  7. Sun Q, Kirnarsky L, Sherman S, Gladyshev V. Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems. Proc Natl Acad Sci U S A. 2001;98:3673-8 pubmed
  8. Leoni S, Kimura E, Santisteban P, De La Vieja A. Regulation of thyroid oxidative state by thioredoxin reductase has a crucial role in thyroid responses to iodide excess. Mol Endocrinol. 2011;25:1924-35 pubmed publisher
  9. Carvalho C, Lu J, Zhang X, Arner E, Holmgren A. Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: implications for treatment of mercury poisoning. FASEB J. 2011;25:370-81 pubmed publisher
    ..These results stress the role of TrxR as a target of mercurials and provide the mechanism of selenite as a detoxification agent for mercury poisoning...
  10. Hashemy S, Ungerstedt J, Zahedi Avval F, Holmgren A. Motexafin gadolinium, a tumor-selective drug targeting thioredoxin reductase and ribonucleotide reductase. J Biol Chem. 2006;281:10691-7 pubmed
    ..This may explain the effects of the drug on cancer cells, which often overproduce TrxR and have induced RNR for replication and repair. ..
  11. Aon Bertolino M, Romero J, Galeano P, Holubiec M, Badorrey M, Saraceno G, et al. Thioredoxin and glutaredoxin system proteins-immunolocalization in the rat central nervous system. Biochim Biophys Acta. 2011;1810:93-110 pubmed publisher
    ..This article is part of a Special Issue entitled Human and Murine Redox Protein Atlases. ..
  12. Mitchell J, Morris A, de Belleroche J. Thioredoxin reductase 1 haplotypes modify familial amyotrophic lateral sclerosis onset. Free Radic Biol Med. 2009;46:202-11 pubmed publisher
    ..The gene TXNRD1 was therefore screened for association with FALS...
  13. Turanov A, Kehr S, Marino S, Yoo M, Carlson B, Hatfield D, et al. Mammalian thioredoxin reductase 1: roles in redox homoeostasis and characterization of cellular targets. Biochem J. 2010;430:285-93 pubmed publisher
    ..Diminished hepatic TR1 function was associated with elevated Trx1 levels, but this protein was mostly in the oxidized state. Overall, this study provides evidence for the key role of the TR1-Trx1 pair in redox homoeostasis. ..
  14. Caprioli J, Munemasa Y, Kwong J, Piri N. Overexpression of thioredoxins 1 and 2 increases retinal ganglion cell survival after pharmacologically induced oxidative stress, optic nerve transection, and in experimental glaucoma. Trans Am Ophthalmol Soc. 2009;107:161-5 pubmed
    ..Thioredoxin overexpression protects RGCs from death after optic nerve axotomy, in pharmacologically induced oxidative stress in vitro and in an animal model of glaucoma. ..
  15. Hama I, Nakagomi S, Konishi H, Kiyama H. Simultaneous expression of glutathione, thioredoxin-1, and their reductases in nerve transected hypoglossal motor neurons of rat. Brain Res. 2010;1306:1-7 pubmed publisher
    ..These data suggest that the two major redox systems, GSH/GSHr and TRX1/TRXr1, are simultaneously activated in injured neurons, and likely provide protection of injured neurons against oxidative stress. ..
  16. Peng X, Mandal P, Kaminskyy V, Lindqvist A, Conrad M, Arnér E. Sec-containing TrxR1 is essential for self-sufficiency of cells by control of glucose-derived H2O2. Cell Death Dis. 2014;5:e1235 pubmed publisher
    ..Here we show that the selenoprotein thioredoxin reductase 1 (TrxR1), encoded by the Txnrd1 gene, is an essential enzyme for such protection...
  17. Yu J, Shan Z, Chong W, Mao J, Geng Y, Zhang C, et al. Vitamin E ameliorates iodine-induced cytotoxicity in thyroid. J Endocrinol. 2011;209:299-306 pubmed publisher
    ..These results show that excess iodine leads to thyroid damage and VE supplementation can partly ameliorate iodine-induced thyroid cytotoxicity. ..
  18. Peng Y, Feng S, Wang Q, Wang H, Hou W, Xiong L, et al. Hyperbaric oxygen preconditioning ameliorates anxiety-like behavior and cognitive impairments via upregulation of thioredoxin reductases in stressed rats. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:1018-25 pubmed publisher
  19. Chandler J, Nichols D, Nick J, Hondal R, Day B. Selective metabolism of hypothiocyanous acid by mammalian thioredoxin reductase promotes lung innate immunity and antioxidant defense. J Biol Chem. 2013;288:18421-8 pubmed publisher
    ..These data support a novel selective mechanism of host defense in mammals wherein HOSCN formation simultaneously inhibits pathogens while sparing host tissue. ..
  20. Narayan V, Kudva A, Prabhu K. Reduction of Tetrathionate by Mammalian Thioredoxin Reductase. Biochemistry. 2015;54:5121-4 pubmed publisher
    ..Here we show that the rat liver selenoenzyme thioredoxin reductase (Txnrd1, TR1) efficiently reduces tetrathionate in vitro...
  21. Jia J, Zhang X, Hu Y, Wu Y, Wang Q, Li N, et al. Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism. Thromb Res. 2009;123:727-30 pubmed publisher
    ..The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription. ..
  22. Jan Y, Heck D, Gray J, Zheng H, Casillas R, Laskin D, et al. Selective targeting of selenocysteine in thioredoxin reductase by the half mustard 2-chloroethyl ethyl sulfide in lung epithelial cells. Chem Res Toxicol. 2010;23:1045-53 pubmed publisher
    ..Taken together, these data suggest that sulfur mustard vesicants target TrxR and that this may be an important mechanism mediating oxidative stress and tissue injury. ..
  23. Iñarrea P, Moini H, Han D, Rettori D, Aguiló I, Alava M, et al. Mitochondrial respiratory chain and thioredoxin reductase regulate intermembrane Cu,Zn-superoxide dismutase activity: implications for mitochondrial energy metabolism and apoptosis. Biochem J. 2007;405:173-9 pubmed
    ..These findings suggest that H2O2, superoxide and TxrR-1 regulate IMS SOD1 activity reversibly, and that the active enzyme is implicated in protecting vital mitochondrial functions. ..
  24. Vesentini N, Barsanti C, Martino A, Kusmic C, Ripoli A, Rossi A, et al. Selection of reference genes in different myocardial regions of an in vivo ischemia/reperfusion rat model for normalization of antioxidant gene expression. BMC Res Notes. 2012;5:124 pubmed publisher
    ..This study provides a validation of reference genes in the RV and in the anterior and posterior wall of the LV of cardiac ischemia/reperfusion model and shows that gene expression should be assessed separately in each region. ..
  25. Furman C, Rundlöf A, Larigauderie G, Jaye M, Bricca G, Copin C, et al. Thioredoxin reductase 1 is upregulated in atherosclerotic plaques: specific induction of the promoter in human macrophages by oxidized low-density lipoproteins. Free Radic Biol Med. 2004;37:71-85 pubmed
  26. Li X, Tang K, Xie B, Li S, Rozanski G. Regulation of Kv4 channel expression in failing rat heart by the thioredoxin system. Am J Physiol Heart Circ Physiol. 2008;295:H416-24 pubmed publisher
    ..These data suggest that the expression of Kv4.x channels is redox-regulated by the thioredoxin system, which may be a novel therapeutic target to reverse or limit electrical remodeling of the failing heart. ..
  27. Rundlöf A, Carlsten M, Giacobini M, Arner E. Prominent expression of the selenoprotein thioredoxin reductase in the medullary rays of the rat kidney and thioredoxin reductase mRNA variants differing at the 5' untranslated region. Biochem J. 2000;347 Pt 3:661-8 pubmed
    ..It can therefore be concluded that TrxR1 mRNA is expressed in at least three different variants that differ at their 5' UTRs. ..
  28. Schulze P, Liu H, Choe E, Yoshioka J, Shalev A, Bloch K, et al. Nitric oxide-dependent suppression of thioredoxin-interacting protein expression enhances thioredoxin activity. Arterioscler Thromb Vasc Biol. 2006;26:2666-72 pubmed
    ..NO can regulate cellular redox state by changing expression of Txnip and thioredoxin reductase. This represents a novel antioxidative mechanism of NO independent of posttranslational protein S-nitrosylation of thioredoxin. ..
  29. Usuki F, Yamashita A, Fujimura M. Post-transcriptional defects of antioxidant selenoenzymes cause oxidative stress under methylmercury exposure. J Biol Chem. 2011;286:6641-9 pubmed publisher
    ..Treatment with ebselen, a seleno-organic compound, effectively suppressed oxidative stress and protected cells against MeHg-induced relative selenium deficiency and cytotoxicity. ..
  30. Fujiwara N, Fujii T, Fujii J, Taniguchi N. Functional expression of rat thioredoxin reductase: selenocysteine insertion sequence element is essential for the active enzyme. Biochem J. 1999;340 ( Pt 2):439-44 pubmed
    ..These data clearly showed a requirement of selenium for the formation of functional TR protein. ..
  31. Anestål K, Prast Nielsen S, Cenas N, Arner E. Cell death by SecTRAPs: thioredoxin reductase as a prooxidant killer of cells. PLoS ONE. 2008;3:e1846 pubmed publisher
    ..SecTRAPs are prooxidant killers of cells, triggering mechanisms beyond those of a mere loss of thioredoxin reductase activity. ..
  32. Bobba A, Casalino E, Petragallo V, Atlante A. Thioredoxin/thioredoxin reductase system involvement in cerebellar granule cell apoptosis. Apoptosis. 2014;19:1497-508 pubmed publisher
    ..When the reduced form of Trx is externally added to apoptotic cultures, a significant reduction in cell death is achieved confirming that a well-functioning thioredoxin/thioredoxin reductase system is required for survival of CGCs. ..
  33. Xu J, Eriksson S, Cebula M, Sandalova T, Hedström E, Pader I, et al. The conserved Trp114 residue of thioredoxin reductase 1 has a redox sensor-like function triggering oligomerization and crosslinking upon oxidative stress related to cell death. Cell Death Dis. 2015;6:e1616 pubmed publisher
  34. Wang K, Zhang J, Wang X, Liu X, Zuo L, Bai K, et al. Thioredoxin reductase was nitrated in the aging heart after myocardial ischemia/reperfusion. Rejuvenation Res. 2013;16:377-85 pubmed publisher
    ..Interventions that inhibit nitration and restore TrxR activity might be a therapy for attenuating enhanced MI/R injury in aging heart. ..
  35. Erkhembayar S, Mollbrink A, Eriksson L. The effect of sodium selenite on liver growth and thioredoxin reductase expression in regenerative and neoplastic liver cell proliferation. Biochem Pharmacol. 2012;83:687-93 pubmed publisher
    ..Furthermore, the over expression of TrxR1 in liver neoplasia can only partly be explained by increased growth. ..
  36. Yang C, Yao C, Lin Y, Yang J, Chien C. Deep-sea water containing selenium provides intestinal protection against duodenal ulcers through the upregulation of Bcl-2 and thioredoxin reductase 1. PLoS ONE. 2014;9:e96006 pubmed publisher
    ..DSW, which contains selenium, provides intestinal protection against duodenal ulcers through the upregulation of Bcl-2 and thioredoxin reductase 1. ..
  37. Shan R, Chang L, Li W, Liu W, Rong Z, Chen Y, et al. Effects of hyperoxia on cytoplasmic thioredoxin system in alveolar type epithelial cells of premature rats. J Huazhong Univ Sci Technolog Med Sci. 2011;31:258-263 pubmed publisher
  38. Yamauchi S, Kiyosawa N, Ando Y, Watanabe K, Niino N, Ito K, et al. Hepatic transcriptome and proteome responses against diethyl maleate-induced glutathione depletion in the rat. Arch Toxicol. 2011;85:1045-56 pubmed publisher
    ..a number of glutathione depletion-responsive genes reported previously, such as Trib3, Srxn1, Myc, Asns, Igfbp1, Txnrd1, or Hmox1, suggesting that these genes are robust mRNA biomarkers for evaluating hepatic glutathione depletion...
  39. Chen W, Tuladhar A, Rolle S, Lai Y, Rodriguez Del Rey F, Zavala C, et al. Brevetoxin-2, is a unique inhibitor of the C-terminal redox center of mammalian thioredoxin reductase-1. Toxicol Appl Pharmacol. 2017;329:58-66 pubmed publisher
    ..PbTx-2 had no effect on the rates of reactions catalyzed by related enzymes such as glutathione reductase, glutathione peroxidase or glutaredoxin. ..
  40. Hodková A, Cerná P, Kotyzova D, Eybl V. The effect of iron(III) on the activity of selenoenzymes and oxidative damage in the liver of rats. Interaction with natural antioxidants and deferiprone. Hemoglobin. 2010;34:278-83 pubmed publisher
    ..Further studies including the combination of synthetic and natural compounds (e.g., flavonoids) are being considered for their possible development and clinical use in antioxidant therapies. ..
  41. Jones M, Mark P, Lewis J, Mori T, Keelan J, Waddell B. Antioxidant defenses in the rat placenta in late gestation: increased labyrinthine expression of superoxide dismutases, glutathione peroxidase 3, and uncoupling protein 2. Biol Reprod. 2010;83:254-60 pubmed publisher
    ..Expression of several genes encoding antioxidant enzymes (Sod1, Sod2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2, and Txnrd3) and Ucp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) ..
  42. Kawai H, Ota T, Suzuki F, Tatsuka M. Molecular cloning of mouse thioredoxin reductases. Gene. 2000;242:321-30 pubmed
    ..71 cR from D10Mit42, lod>3.0) and the TrxR2 gene to chromosome 16 (placed 22.56 cR from D16Mit34, lod>3.0). Thus, the mouse has at least two distinct nuclear genes for TrxR that have different translocation sites in the cell. ..
  43. Zhao X, Zhao J, Li X, Zhang Y, Jiao X. [The change of thioredoxin system in myocardial tissue of type 2 diabetic rats undergoing myocardial injury]. Sheng Li Xue Bao. 2010;62:261-8 pubmed
    ..These results suggest diabetes can decrease myocardial Trx, TR activity, inducing myocardial cell apoptosis and heart injury. The inhibitory effect of diabetes is mainly associated with TXNIP up-regulation and Trx nitration. ..
  44. Aranibar N, Bhaskaran V, Ott K, Vassallo J, Nelson D, Lecureux L, et al. Modulation of ascorbic acid metabolism by cytochrome P450 induction revealed by metabonomics and transcriptional profiling. Magn Reson Chem. 2009;47 Suppl 1:S12-9 pubmed publisher
    ..enzymes regulating ascorbic acid reutilization including glutaredoxin reductase (Glrx2) and thioredoxin reductase (Txnrd1)...
  45. Venardos K, Ashton K, Headrick J, Perkins A. Effects of dietary selenium on post-ischemic expression of antioxidant mRNA. Mol Cell Biochem. 2005;270:131-8 pubmed
    ..Our results show selenium modulates the cardiac mRNA expression of thioredoxin and glutathione related enzymes post ischemia-reperfusion, and impacts on tolerance to ischemia-reperfusion. ..
  46. Wang L, Jiang D. Neuroprotective effect of Buyang Huanwu Decoction on spinal ischemia/reperfusion injury in rats. J Ethnopharmacol. 2009;124:219-23 pubmed publisher
    ..Our results suggest that administration of Buyang Huanwu Decoction may reduce spinal ischemia/reperfusion damage. This neuroprotective effect may be mediated, in part, by an increase in the transcription of thioredoxin. ..
  47. Jeong W, Yoon H, Lee S, Rhee S. Identification and characterization of TRP14, a thioredoxin-related protein of 14 kDa. New insights into the specificity of thioredoxin function. J Biol Chem. 2004;279:3142-50 pubmed
    ..These results suggest that TRP14 and Trx1 might act on distinct substrate proteins. ..
  48. Wang J, Rahman M, Duhart H, Newport G, Patterson T, Murdock R, et al. Expression changes of dopaminergic system-related genes in PC12 cells induced by manganese, silver, or copper nanoparticles. Neurotoxicology. 2009;30:926-33 pubmed publisher
    ..The expression of Txnrd1 was up-regulated after the Cu-90 treatment and the expression of Gpx1 was down-regulated after Ag-15 or Cu-90 ..
  49. Dagnell M, Pace P, Cheng Q, Frijhoff J, Ostman A, Arner E, et al. Thioredoxin reductase 1 and NADPH directly protect protein tyrosine phosphatase 1B from inactivation during H2O2 exposure. J Biol Chem. 2017;292:14371-14380 pubmed publisher
    ..The activity of TrxR1 is therefore of potential relevance for understanding the mechanisms of redox regulation of growth factor signaling pathways. ..