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Gene Review

Gsr  -  glutathione reductase

Mus musculus

Synonyms: AI325518, D8Ertd238e, GR, GRase, Glutathione reductase, mitochondrial, ...
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Disease relevance of Gsr


High impact information on Gsr

  • Glutathione peroxidase activity and mRNA level, glutathione reductase activity, and reduced glutathione levels were all transiently increased in hydroxyurea-treated cells, whereas the increase in glutathione-S-transferase activity was sustained [6].
  • The effect of glutathione and a glutathione reductase inhibitor on the antitumor effect of Cu(II)(3,5-diisopropylsalicylate)2 (CuDIPS) was studied [7].
  • Studies of B6 Csf1(op/op) (lacking macrophages) mice, Rag1(-/-) mice, and wild-type mice treated with neutrophil-specific Gr1 mAbs, disclosed that macrophages but not lymphocytes or neutrophils are necessary [8].
  • We propose that the oxidation of glutathione proceeds by reaction with protein disulfide groups to yield protein sulfhydryl (PSH) and a mixed disulfide of glutathione and protein; the mixed disulfide is capable of being reduced by glutathione reductase and NADPH, yielding the original PSH and GSSG, which is extruded from the lens [9].
  • The LETS protein segregated concordantly with the chromosome 8 enzyme marker glutathione reductase (EC and human chromosome 8 [10].

Chemical compound and disease context of Gsr


Biological context of Gsr


Anatomical context of Gsr


Associations of Gsr with chemical compounds


Enzymatic interactions of Gsr


Regulatory relationships of Gsr


Other interactions of Gsr

  • GPx and catalase activities slowly went down, while GRed continued increasing as long as the levels of GSH were kept very low [33].
  • After tumor transplantation and treatment with the complexes, the activities of GSH-Px and GSH-R were significantly lowered while SOD and G6PD activities were increased in EAC cells compared to their levels in EAC cells harvested from saline-treated mice [34].
  • Aqueous black tea extract was given as a pretreatment to group IV mice at a dose of 200 mg ml(-1) polyphenols before the pesticide dose, which significantly decreased the levels of lipid peroxidation and significantly elevated the activities of SOD, CAT, GSH, total thiol, GPx, GR and GST in liver to levels similar to the controls [35].
  • Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice [36].
  • The DKO cells had lower (P < 0.05) microsomal cytochrome P450 2E1 activities, but higher (P < 0.05) glutathione reductase and thioredoxin reductase activities than the WT cells at 0 hrs, and they responded differently to the APAP and NAPQI treatments [37].

Analytical, diagnostic and therapeutic context of Gsr

  • The GR activity was only increased in the presence of 50 mug/ml of SRG compared to the control group [38].
  • Erythrocyte and organo-somatic indices did not show differences between wild-types and homozygous mutants, indicating no association between the GR deficiency and haemolytic anaemia in this potential animal model [39].
  • The molecular cloning of a partial cDNA to mouse glutathione reductase mRNA and of a full-length cDNA to the mRNA of the human enzyme is described [24].
  • RT-PCR of mRNA from the Neu mice indicated a substantial deletion in the normal GR coding sequence [40].
  • No significant changes were observed for superoxide dismutase, catalase, glutathione reductase, glutathione, uric acid, malondialdehyde (HPLC), or in vitro sensitivity to peroxidation in the kidney [41].


  1. Glutathione peroxidase and glutathione reductase activities are partially responsible for determining the susceptibility of cells to oxidative stress. Yang, M.S., Chan, H.W., Yu, L.C. Toxicology (2006) [Pubmed]
  2. Enhanced oxygen toxicity following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea. Kehrer, J.P., Paraidathathu, T. Fundamental and applied toxicology : official journal of the Society of Toxicology. (1984) [Pubmed]
  3. Assembly and functional expression of murine glutathione reductase cDNA: a sequence missing in expressed sequence tag libraries. Iozef, R., Becker, K., Boehme, C.C., Schirmer, R.H., Werner, D. Biochim. Biophys. Acta (2000) [Pubmed]
  4. Metabolism of mutagens and carcinogens in woodchuck liver and its relationship with hepatitis virus infection. De Flora, S., Camoirano, A., Romano, M., Astengo, M., Cesarone, C.F., Millman, I. Cancer Res. (1987) [Pubmed]
  5. Enhancement of the antineoplastic effect of mitomycin C by dietary fat. Shao, Y., Pardini, L., Pardini, R.S. Cancer Res. (1994) [Pubmed]
  6. Role of antioxidant enzymes in the induction of increased experimental metastasis by hydroxyurea. Eskenazi, A.E., Pinkas, J., Whitin, J.C., Arguello, F., Cohen, H.J., Frantz, C.N. J. Natl. Cancer Inst. (1993) [Pubmed]
  7. Possible role of glutathione in the antitumor effect of a copper-containing synthetic superoxide dismutase in mice. Oberley, L.W., Rogers, K.L., Schutt, L., Oberley, T.D., Leuthauser, S.W., Sorenson, J.R. J. Natl. Cancer Inst. (1983) [Pubmed]
  8. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Pull, S.L., Doherty, J.M., Mills, J.C., Gordon, J.I., Stappenbeck, T.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Disulfide bond formation in the eye lens. Yu, N.T., DeNagel, D.C., Pruett, P.L., Kuck, J.F. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  10. Genetics of the large, external, transformation-sensitive (LETS) protein: assignment of a gene coding for expression of LETS to human chromosome 8. Owerbach, D., Doyle, D., Shows, T.B. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  11. Prion protein-deficient neurons reveal lower glutathione reductase activity and increased susceptibility to hydrogen peroxide toxicity. White, A.R., Collins, S.J., Maher, F., Jobling, M.F., Stewart, L.R., Thyer, J.M., Beyreuther, K., Masters, C.L., Cappai, R. Am. J. Pathol. (1999) [Pubmed]
  12. Acidosis potentiates oxidative neuronal death by multiple mechanisms. Ying, W., Han, S.K., Miller, J.W., Swanson, R.A. J. Neurochem. (1999) [Pubmed]
  13. Glutathione and non-protein sulfhydryl in cerebral cortex and lung in mice exposed to high oxygen pressure. Waechter, J.M., Faiman, M.D. Toxicology (1982) [Pubmed]
  14. Changes in glutathione-related enzymes in tumor-bearing mice after cisplatin treatment. Khynriam, D., Prasad, S.B. Cell Biol. Toxicol. (2002) [Pubmed]
  15. Study of oxidative-stress in rotavirus infected infant mice. Sodhi, C.P., Katyal, R., Rana, S.V., Attri, S., Singh, V. Indian J. Med. Res. (1996) [Pubmed]
  16. Spontaneous hypomorphic mutations in antioxidant enzymes of mice. Guo, Z., Higuchi, K., Mori, M. Free Radic. Biol. Med. (2003) [Pubmed]
  17. Melatonin reduces oxidative stress in erythrocytes and plasma of senescence-accelerated mice. Nogués, M.R., Giralt, M., Romeu, M., Mulero, M., Sánchez-Martos, V., Rodríguez, E., Acuña-Castroviejo, D., Mallol, J. J. Pineal Res. (2006) [Pubmed]
  18. Antioxidative effects of Cinnamomi cassiae and Rhodiola rosea extracts in liver of diabetic mice. Kim, S.H., Hyun, S.H., Choung, S.Y. Biofactors (2006) [Pubmed]
  19. Activity and gene expression profile of certain antioxidant enzymes to microcystin-LR induced oxidative stress in mice. Jayaraj, R., Anand, T., Rao, P.V. Toxicology (2006) [Pubmed]
  20. Dehydroascorbic acid prevents oxidative cell death through a glutathione pathway in primary astrocytes. Kim, E.J., Park, Y.G., Baik, E.J., Jung, S.J., Won, R., Nahm, T.S., Lee, B.H. J. Neurosci. Res. (2005) [Pubmed]
  21. Oxidative stress in mouse brain exposed to lead. Wang, J., Wu, J., Zhang, Z. The Annals of occupational hygiene. (2006) [Pubmed]
  22. Dose-response effects of acute ultraviolet irradiation on antioxidants and molecular markers of oxidation in murine epidermis and dermis. Shindo, Y., Witt, E., Han, D., Packer, L. J. Invest. Dermatol. (1994) [Pubmed]
  23. Comparison of the susceptibility of hepatocytes from postnatal and adult mice to hepatotoxins. Adamson, G.M., Harman, A.W. Biochem. Pharmacol. (1988) [Pubmed]
  24. Cloning and sequencing of mammalian glutathione reductase cDNA. Tutic, M., Lu, X.A., Schirmer, R.H., Werner, D. Eur. J. Biochem. (1990) [Pubmed]
  25. Gene structure for mouse glutathione reductase, including a putative mitochondrial targeting signal. Tamura, T., McMicken, H.W., Smith, C.V., Hansen, T.N. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  26. Antioxidant enzyme response to hypericin in EMT6 mouse mammary carcinoma cells. Johnson, S.A., Pardini, R.S. Free Radic. Biol. Med. (1998) [Pubmed]
  27. Modulatory influence of Adhatoda vesica (Justicia adhatoda) leaf extract on the enzymes of xenobiotic metabolism, antioxidant status and lipid peroxidation in mice. Singh, R.P., Padmavathi, B., Rao, A.R. Mol. Cell. Biochem. (2000) [Pubmed]
  28. Antioxidant enzyme activities in lens, liver and kidney of calorie restricted Emory mice. Gong, X., Shang, F., Obin, M., Palmer, H., Scrofano, M.M., Jahngen-Hodge, J., Smith, D.E., Taylor, A. Mech. Ageing Dev. (1997) [Pubmed]
  29. Thioredoxin reductase and glutathione synthesis is upregulated by t-butylhydroquinone in cortical astrocytes but not in cortical neurons. Eftekharpour, E., Holmgren, A., Juurlink, B.H. Glia (2000) [Pubmed]
  30. Endotoxin induces glutathione reductase activity in lungs of mice. Hamburg, D.C., Tonoki, H., Welty, S.E., Geske, R.S., Montgomery, C.A., Hansen, T.N. Pediatr. Res. (1994) [Pubmed]
  31. Effects of resveratrol on 12-O-tetradecanoylphorbol-13-acetate-induced oxidative events and gene expression in mouse skin. Jang, M., Pezzuto, J.M. Cancer Lett. (1998) [Pubmed]
  32. Microphotometric study of glucose-6-phosphate dehydrogenase activity in epididymal spermatozoa during spontaneous lipid peroxidation. Ferrandi, B., Lange Consiglio, A., Carnevali, A., Porcelli, F. Acta Histochem. (1990) [Pubmed]
  33. Protoporphyrin IX and oxidative stress. Afonso, S., Vanore, G., Batlle, A. Free Radic. Res. (1999) [Pubmed]
  34. Antitumor activities of vanadium(IV), manganese(IV), iron(III), cobalt(II) and copper(II) complexes of 2-methylaminopyridine. El-Naggar, M.M., El-Waseef, A.M., El-Halafawy, K.M., El-Sayed, I.H. Cancer Lett. (1998) [Pubmed]
  35. Protective effect of black tea extract on the levels of lipid peroxidation and antioxidant enzymes in liver of mice with pesticide-induced liver injury. Khan, S.M. Cell Biochem. Funct. (2006) [Pubmed]
  36. Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice. Hovatta, I., Tennant, R.S., Helton, R., Marr, R.A., Singer, O., Redwine, J.M., Ellison, J.A., Schadt, E.E., Verma, I.M., Lockhart, D.J., Barlow, C. Nature (2005) [Pubmed]
  37. Double null of selenium-glutathione peroxidase-1 and copper, zinc-superoxide dismutase enhances resistance of mouse primary hepatocytes to acetaminophen toxicity. Zhu, J.H., Lei, X.G. Exp. Biol. Med. (Maywood) (2006) [Pubmed]
  38. Rehmannia glutinosa Activates Intracellular Antioxidant Enzyme Systems in Mouse Auditory Cells. Yu, H.H., Kim, Y.H., Jung, S.Y., Shin, M.K., Park, R.K., So, H.S., Kim, K.Y., Lee, D.H., You, Y.O. Am. J. Chin. Med. (2006) [Pubmed]
  39. Glutathione reductase activity deficiency in homozygous Gr1a1Neu mice does not cause haemolytic anaemia. Pretsch, W. Genet. Res. (1999) [Pubmed]
  40. Analyses of glutathione reductase hypomorphic mice indicate a genetic knockout. Rogers, L.K., Tamura, T., Rogers, B.J., Welty, S.E., Hansen, T.N., Smith, C.V. Toxicol. Sci. (2004) [Pubmed]
  41. Caloric and carbohydrate restriction in the kidney: effects on free radical metabolism. Cadenas, S., Rojas, C., Pérez-Campo, R., López-Torres, M., Barja, G. Exp. Gerontol. (1994) [Pubmed]
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