Gene Symbol: Txnrd1
Description: thioredoxin reductase 1
Alias: TR1, TrxR1, thioredoxin reductase 1, cytoplasmic, TR alpha, thioredoxin reductase TR1
Species: mouse
Products:     Txnrd1

Top Publications

  1. Dagnell M, Frijhoff J, Pader I, Augsten M, Boivin B, Xu J, et al. Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-? receptor tyrosine kinase signaling. Proc Natl Acad Sci U S A. 2013;110:13398-403 pubmed publisher
    ..Cells lacking the major Trx reductase TrxR1 (Txnrd1(-/-)) displayed increased oxidation of PTP1B, whereas SHP2 oxidation was unchanged...
  2. 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
    ..Three TRs have been identified in mammals: (i) cytosolic TR1, (ii) mitochondrial TR3 and (iii) testes-specific TGR (Trx-glutathione reductase)...
  3. Conrad M. Transgenic mouse models for the vital selenoenzymes cytosolic thioredoxin reductase, mitochondrial thioredoxin reductase and glutathione peroxidase 4. Biochim Biophys Acta. 2009;1790:1575-85 pubmed publisher
    ..Later on, systemic ablation of cytosolic thioredoxin reductase (Txnrd1) or mitochondrial thioredoxin reductase (Txnrd2) yielded embryonic lethal phenotypes...
  4. Yoo M, Xu X, Carlson B, Patterson A, Gladyshev V, Hatfield D. Targeting thioredoxin reductase 1 reduction in cancer cells inhibits self-sufficient growth and DNA replication. PLoS ONE. 2007;2:e1112 pubmed
    Thioredoxin reductase 1 (TR1) is a major redox regulator in mammalian cells. As an important antioxidant selenoprotein, TR1 is thought to participate in cancer prevention, but is also known to be over-expressed in many cancer cells...
  5. Kawai H, Ota T, Suzuki F, Tatsuka M. Molecular cloning of mouse thioredoxin reductases. Gene. 2000;242:321-30 pubmed
    ..These encode two distinct thioredoxin reductases (TrxR1 and TrxR2) with 499 and 527 amino acid (aa) residues and calculated molecular masses of 54.5 kDa and 56...
  6. Mandal P, Schneider M, Kölle P, Kuhlencordt P, Forster H, Beck H, et al. Loss of thioredoxin reductase 1 renders tumors highly susceptible to pharmacologic glutathione deprivation. Cancer Res. 2010;70:9505-14 pubmed publisher
    ..Trx1 and thioredoxin reductase 1 (Txnrd1) are upregulated in numerous cancers, and Txnrd1 has been reported to be indispensable for tumorigenesis...
  7. Rollins M, van der Heide D, Weisend C, Kundert J, Comstock K, Suvorova E, et al. Hepatocytes lacking thioredoxin reductase 1 have normal replicative potential during development and regeneration. J Cell Sci. 2010;123:2402-12 pubmed publisher
    ..We have studied proliferation of thioredoxin-reductase-1 (Txnrd1)-deficient hepatocytes in mice...
  8. Soerensen J, Jakupoglu C, Beck H, Forster H, Schmidt J, Schmahl W, et al. The role of thioredoxin reductases in brain development. PLoS ONE. 2008;3:e1813 pubmed publisher
    ..the roles of thioredoxin reductases in brain using mice with nervous system (NS)-specific deletion of cytosolic (Txnrd1) and mitochondrial (Txnrd2) thioredoxin reductase...
  9. 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...

More Information


  1. Sun Q, Wu Y, Zappacosta F, Jeang K, Lee B, Hatfield D, et al. Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases. J Biol Chem. 1999;274:24522-30 pubmed
    ..Two mammalian TR isozymes (TR2 and TR3), in addition to that previously characterized (TR1), have now been identified in humans and mice...
  2. Prigge J, Eriksson S, Iverson S, Meade T, Capecchi M, Arner E, et al. Hepatocyte DNA replication in growing liver requires either glutathione or a single allele of txnrd1. Free Radic Biol Med. 2012;52:803-10 pubmed publisher
    ..thioredoxin reductase 1 (TrxR1) are embryonic-lethal, several studies have shown that mouse cells lacking the txnrd1 gene, encoding TrxR1, can proliferate normally...
  3. Sun Q, Zappacosta F, Factor V, Wirth P, Hatfield D, Gladyshev V. Heterogeneity within animal thioredoxin reductases. Evidence for alternative first exon splicing. J Biol Chem. 2001;276:3106-14 pubmed
    ..Three types of mammalian TRs are known, with TR1 being a cytosolic enzyme, and TR3, a mitochondrial enzyme...
  4. Mandal P, Seiler A, Perisic T, Kölle P, Banjac Canak A, Forster H, et al. System x(c)- and thioredoxin reductase 1 cooperatively rescue glutathione deficiency. J Biol Chem. 2010;285:22244-53 pubmed publisher
  5. Carlson B, Yoo M, Tobe R, Mueller C, Naranjo Suarez S, Hoffmann V, et al. Thioredoxin reductase 1 protects against chemically induced hepatocarcinogenesis via control of cellular redox homeostasis. Carcinogenesis. 2012;33:1806-13 pubmed publisher
    Thioredoxin reductase 1 (TR1) controls the redox state of protein thiols in mammalian cells and has been shown to have roles in both preventing and promoting cancer...
  6. Tobe R, Yoo M, Fradejas N, Carlson B, Calvo S, Gladyshev V, et al. Thioredoxin reductase 1 deficiency enhances selenite toxicity in cancer cells via a thioredoxin-independent mechanism. Biochem J. 2012;445:423-30 pubmed publisher
    ..stress, and the Trx (thioredoxin) system is a major antioxidative system, we examined the interplay between TR1 (Trx reductase 1) and Trx1 deficiencies and selenite toxicity in DT cells, a malignant mouse cell line, and the ..
  7. 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
    ..Previously a neuroblastoma-cell-derived 2193 bp cDNA for rat thioredoxin reductase 1 (TrxR1) was characterized [Zhong, Arnér, Ljung, Aslund and Holmgren (1998) J. Biol. Chem. 273, 8581-8591]...
  8. 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
  9. Suvorova E, Lucas O, Weisend C, Rollins M, Merrill G, Capecchi M, et al. Cytoprotective Nrf2 pathway is induced in chronically txnrd 1-deficient hepatocytes. PLoS ONE. 2009;4:e6158 pubmed publisher
    ..The cytoplasmic thioredoxin reductase/thioredoxin (Txnrd1/Txn1) system maintains reduced protein dithiols and provides electrons to some cellular reductases, including ..
  10. Jin R, Gao Y, Zhang S, Teng F, Xu X, Aili A, et al. Trx1/TrxR1 system regulates post-selected DP thymocytes survival by modulating ASK1-JNK/p38 MAPK activities. Immunol Cell Biol. 2015;93:744-52 pubmed publisher
    ..Biochemically, treatment of DP thymcoytes with TrxR1 inhibitor alone or in conjunction with anti-CD3 resulted in enhanced phosphorylation of redox-sensitive ASK-1, JNK ..
  11. Cunniff B, Snider G, Fredette N, Stumpff J, Hondal R, Heintz N. Resolution of oxidative stress by thioredoxin reductase: Cysteine versus selenocysteine. Redox Biol. 2014;2:475-84 pubmed publisher
    ..and reactivation of PRXs in mouse C10 cells expressing various isoforms of TR, including wild type cytoplasmic TR1 (Sec-TR1) and mitochondrial TR2 (Sec-TR2) that encode selenocysteine, as well as mutants of TR1 and TR2 in which ..
  12. Osborne S, Tonissen K. Genomic organisation and alternative splicing of mouse and human thioredoxin reductase 1 genes. BMC Genomics. 2001;2:10 pubmed
    ..In this study we elucidated the genomic organisation of the mouse (Txnrd1) and human thioredoxin reductase 1 genes (TXNRD1) through library screening, restriction mapping and database ..
  13. Lam J, Chow K, Xu A, Lam K, Liu J, Wong N, et al. Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities. PLoS ONE. 2009;4:e4968 pubmed publisher
    ..The activities of thioredoxin (Trx1) and thioredoxin reductase (TrxR1) were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or ..
  14. Sengupta A, Lichti U, Carlson B, Cataisson C, Ryscavage A, Mikulec C, et al. Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2. J Invest Dermatol. 2013;133:1731-41 pubmed publisher
    ..Keratinocyte-specific knockout mice lacking either the glutathione peroxidase 4 (GPx4) or thioredoxin reductase 1 (TR1) gene were generated by cre-lox technology using K14-cre...
  15. Liu J, Mu C, Yue W, Li J, Ma B, Zhao L, et al. A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis. Free Radic Biol Med. 2013;63:485-94 pubmed publisher
    ..Here, we identify that S3 targets the selenoproteins TrxR1 and TrxR2 at the selenocysteine residue of the reactive center of the enzymes and inhibits their antioxidant ..
  16. Britt R, Velten M, Locy M, Rogers L, Tipple T. The thioredoxin reductase-1 inhibitor aurothioglucose attenuates lung injury and improves survival in a murine model of acute respiratory distress syndrome. Antioxid Redox Signal. 2014;20:2681-91 pubmed publisher
    ..in vitro and attenuated adult murine hyperoxic lung injury in vivo after pharmacological thioredoxin reductase-1 (TrxR1) inhibition...
  17. Brewer A, Murray T, Arno M, Zhang M, Anilkumar N, Mann G, et al. Nox4 regulates Nrf2 and glutathione redox in cardiomyocytes in vivo. Free Radic Biol Med. 2011;51:205-15 pubmed publisher
    ..These data therefore demonstrate that Nox4 can activate the Nrf2-regulated pathway, and suggest a potential role for Nox4 in the regulation of GSH redox in cardiomyocytes. ..
  18. Tipple T, Welty S, Nelin L, Hansen J, Rogers L. Alterations of the thioredoxin system by hyperoxia: implications for alveolar development. Am J Respir Cell Mol Biol. 2009;41:612-9 pubmed publisher
    ..The inverse correlation of Txnip with VEGF expression suggests that decreased Trx1 function contributes to the observed lung developmental abnormalities. ..
  19. Snider G, Ruggles E, Khan N, Hondal R. Selenocysteine confers resistance to inactivation by oxidation in thioredoxin reductase: comparison of selenium and sulfur enzymes. Biochemistry. 2013;52:5472-81 pubmed publisher
  20. Eriksson S, Prigge J, Talago E, Arnér E, Schmidt E. Dietary methionine can sustain cytosolic redox homeostasis in the mouse liver. Nat Commun. 2015;6:6479 pubmed publisher
    ..adenine dinucleotide phosphate (NADPH) transfers intracellular reducing power to thioredoxin reductase-1 (TrxR1) and glutathione reductase (GR), thereby supporting fundamental housekeeping and antioxidant pathways...
  21. Peng X, Giménez Cassina A, Petrus P, Conrad M, Rydén M, Arnér E. Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness. Sci Rep. 2016;6:28080 pubmed publisher
    Recently thioredoxin reductase 1 (TrxR1), encoded by Txnrd1, was suggested to modulate glucose and lipid metabolism in mice...
  22. Carlson B, Yoo M, Conrad M, Gladyshev V, Hatfield D, Park J. Protein kinase-regulated expression and immune function of thioredoxin reductase 1 in mouse macrophages. Mol Immunol. 2011;49:311-6 pubmed publisher
    ..incorporation of radiolabeled selenium into protein during LPS stimulation, and identified thioredoxin reductase 1 (TR1) as the only LPS-inducible selenoprotein in macrophages...
  23. Yoo M, Carlson B, Gladyshev V, Hatfield D. Abrogated thioredoxin system causes increased sensitivity to TNF-?-induced apoptosis via enrichment of p-ERK 1/2 in the nucleus. PLoS ONE. 2013;8:e71427 pubmed publisher
    Thioredoxin (Trx) and thioredoxin reductase 1 (TR1) are among the major redox regulators in mammalian cells and have a wide variety of roles, including removal of intracellular reactive oxygen species (ROS) and prevention of cell death...
  24. Kang J, Kim G, Kim B, Choi Y. Antioxidative effects of diallyl trisulfide on hydrogen peroxide-induced cytotoxicity through regulation of nuclear factor-E2-related factor-mediated thioredoxin reductase 1 expression in C2C12 skeletal muscle myoblast cells. Gen Physiol Biophys. 2017;36:129-139 pubmed publisher
    ..upregulated the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and thioredoxin reductase 1 (TrxR1), which was associated with the increased phosphorylation of Nrf2...
  25. Li Q, Wall S, Ren C, Velten M, Hill C, Locy M, et al. Thioredoxin Reductase Inhibition Attenuates Neonatal Hyperoxic Lung Injury and Enhances Nuclear Factor E2-Related Factor 2 Activation. Am J Respir Cell Mol Biol. 2016;55:419-28 pubmed publisher
    ..Aurothioglucose (ATG) and auranofin potently inhibit thioredoxin reductase-1 (TrxR1), and TrxR1 disruption activates nuclear factor E2-related factor 2 (Nrf2), a regulator of endogenous antioxidant ..
  26. Gerashchenko M, Su D, Gladyshev V. CUG start codon generates thioredoxin/glutathione reductase isoforms in mouse testes. J Biol Chem. 2010;285:4595-602 pubmed publisher
    ..This study shows that CUG codon is used as an inefficient start codon to generate protein isoforms in mouse...
  27. Chung Y, Jeong D, Noh O, Park Y, Kang S, Lee M, et al. Antioxidative role of selenoprotein W in oxidant-induced mouse embryonic neuronal cell death. Mol Cells. 2009;27:609-13 pubmed publisher
    ..Taken together, our findings suggest that SelW plays an important role in protection of neurons from oxidative stress during neuronal development. ..
  28. Kelly V, Suzuki T, Nakajima O, Arai T, Tamai Y, Takahashi S, et al. The distal sequence element of the selenocysteine tRNA gene is a tissue-dependent enhancer essential for mouse embryogenesis. Mol Cell Biol. 2005;25:3658-69 pubmed
    ..Together, our data demonstrate that the DSE is a tissue-dependent regulatory element of tRNA(Sec) expression and that its activity is vital for sufficient tRNA(Sec) production during mouse embryogenesis. ..
  29. Iverson S, Eriksson S, Xu J, Prigge J, Talago E, Meade T, et al. A Txnrd1-dependent metabolic switch alters hepatic lipogenesis, glycogen storage, and detoxification. Free Radic Biol Med. 2013;63:369-80 pubmed publisher
    ..We show that hepatocyte-specific disruption of Txnrd1, encoding Trx reductase-1 (TrxR1), causes a metabolic switch in which lipogenic genes are repressed and periportal ..
  30. Naranjo Suarez S, Carlson B, Tsuji P, Yoo M, Gladyshev V, Hatfield D. HIF-independent regulation of thioredoxin reductase 1 contributes to the high levels of reactive oxygen species induced by hypoxia. PLoS ONE. 2012;7:e30470 pubmed publisher
    ..Here, we show that hypoxia downregulates thioredoxin reductase 1 (TR1) mRNA and protein levels...
  31. Kurokawa S, Eriksson S, Rose K, Wu S, Motley A, Hill S, et al. Sepp1(UF) forms are N-terminal selenoprotein P truncations that have peroxidase activity when coupled with thioredoxin reductase-1. Free Radic Biol Med. 2014;69:67-76 pubmed publisher
    ..were compared with full-length Sepp1, Sepp1(?240-361), and Sepp1(U40S) as a substrate of thioredoxin reductase-1 (TrxR1)...
  32. 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...
  33. Kiermayer C, Michalke B, Schmidt J, Brielmeier M. Effect of selenium on thioredoxin reductase activity in Txnrd1 or Txnrd2 hemizygous mice. Biol Chem. 2007;388:1091-7 pubmed
    Thioredoxin reductase 1 (Txnrd1) and thioredoxin reductase 2 (Txnrd2) are selenoproteins whose expression and function depends on adequate supply of the trace element selenium (Se)...
  34. 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. ..
  35. Singh M, Kwak G, Kim K, Kim H. Methionine sulfoxide reductase A protects hepatocytes against acetaminophen-induced toxicity via regulation of thioredoxin reductase 1 expression. Biochem Biophys Res Commun. 2017;487:695-701 pubmed publisher
    Thioredoxin reductase 1 (TXNRD1) is associated with susceptibility to acetaminophen (APAP)-induced liver damage...
  36. Tsuji P, Carlson B, Yoo M, Naranjo Suarez S, Xu X, He Y, et al. The 15kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways. PLoS ONE. 2015;10:e0124487 pubmed publisher
    ..We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development...
  37. Hintze K, Katoh Y, Igarashi K, Theil E. Bach1 repression of ferritin and thioredoxin reductase1 is heme-sensitive in cells and in vitro and coordinates expression with heme oxygenase1, beta-globin, and NADP(H) quinone (oxido) reductase1. J Biol Chem. 2007;282:34365-71 pubmed
  38. Han C, Kim M, Ding D, Park H, White K, Walker L, et al. GSR is not essential for the maintenance of antioxidant defenses in mouse cochlea: Possible role of the thioredoxin system as a functional backup for GSR. PLoS ONE. 2017;12:e0180817 pubmed publisher
    ..Given that the thioredoxin system is known to reduce GSSG to GSH in multiple species, our findings suggest that the thioredoxin system can support GSSG reduction in the mouse peripheral auditory system. ..
  39. Sun K, Eriksson S, Tan Y, Zhang L, Arner E, Zhang J. Serum thioredoxin reductase levels increase in response to chemically induced acute liver injury. Biochim Biophys Acta. 2014;1840:2105-11 pubmed publisher
    ..Serum TrxR levels were determined with immunoblotting using antibodies against mouse TrxR1 and total enzyme activity measurements were performed, with serum and tissue samples from mouse models of liver ..
  40. Prigge J, Coppo L, Martin S, Ogata F, Miller C, Bruschwein M, et al. Hepatocyte Hyperproliferation upon Liver-Specific Co-disruption of Thioredoxin-1, Thioredoxin Reductase-1, and Glutathione Reductase. Cell Rep. 2017;19:2771-2781 pubmed publisher
    ..NADPH-dependent reduction of thioredoxin-1 (Trx1) disulfide and glutathione disulfide by thioredoxin reductase-1 (TrxR1) and glutathione reductase (Gsr), respectively, fuels antioxidant systems and deoxyribonucleotide synthesis...