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Gene Review

Gpx1  -  glutathione peroxidase 1

Mus musculus

Synonyms: AI195024, AL033363, CGPx, Cellular glutathione peroxidase, GPx-1, ...
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Disease relevance of Gpx1

  • Because genetic background affects tumor susceptibility, we have generated a B6 Gpx1/2-DKO colony and discovered that these mice have fewer inflammatory cells, milder ileocolitis, and low mortality, and only 2.5% of B6 mice developed tumors [1].
  • Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes [2].
  • We have previously demonstrated that targeted disruption of both the Gpx1 and Gpx2 genes (GPX-DKO) results in a high incidence of ileocolitis in mice raised under conventional conditions, which include the harboring of Helicobacter species [non-specific-pathogen-free (non-SPF) conditions] [2].
  • We further demonstrate that paraquat transcriptionally up-regulates Gpx1 in normal cells, reinforcing a role for Gpx1 in protection against paraquat toxicity [3].
  • Further, they emphasize the need to elucidate the role of Gpx1 in protection against different oxidative stressors and in different disease states and suggest that Gpx1 (-/-) mice may be valuable for studying the role of H2O2 in neurodegenerative disorders [3].

Psychiatry related information on Gpx1


High impact information on Gpx1


Chemical compound and disease context of Gpx1


Biological context of Gpx1

  • The mutation spectra analysis has shown that B6 Gpx1/2-DKO ileum had a 3-fold increase in small nucleotide deletions at mononucleotide repeats over control B6, which are a signature mutation associated with oxidative stress [1].
  • The mutant frequency of a cII reporter gene was about 2- to 3-fold higher in 28-day-old Gpx1/2-DKO and 4-fold higher in 8-month-old Gpx1/2-DKO ileal mucosa than in controls in both genetic backgrounds [1].
  • Increased levels of cell death were detected in cells lacking Gpx1 following the addition of exogenous H2O2 [13].
  • Similarly, endogenous oxidative stress induced by cardiac ischemia/reperfusion injury led to greater apoptosis in heart tissue from the Sod2(+/-)/Gpx1(-/-) mice than in that from mice deficient in either MnSOD or Gpx1 alone [14].
  • Therefore, our results suggest that the increased susceptibility of Gpx1-/- cells to H2O2-induced apoptosis can be attributed in part to diminished activation of Akt despite an up-regulation in the activation of the prosurvival NFkappaB [13].

Anatomical context of Gpx1

  • Our results suggest that inflammation drives gene mutations, which leads to neoplastic transformation of intestinal epithelium in the B6.129 Gpx1/2-DKO mice but rarely in the B6 Gpx1/2-DKO mice [1].
  • These experiments revealed that Gpx1 is highly expressed in both the mitochondria and the cytosol of the liver and kidney, but poorly expressed in heart and muscle [15].
  • Fibroblasts derived from Gpx1 knockout mice display senescent-like features and are susceptible to H2O2-mediated cell death [16].
  • Moreover, the liver mitochondria were found to release markedly increased hydrogen peroxide, a Gpx1 substrate, and have decreased mitochondrial respiratory control ratio and power output index [15].
  • After 12 weeks of HFD, atherosclerotic lesions at the aortic sinus were of similar size in control and Gpx1-deficient mice [17].

Associations of Gpx1 with chemical compounds


Physical interactions of Gpx1


Regulatory relationships of Gpx1

  • This is the first report that a particular isotype of the glutathione peroxidase family is regulated by TCDD at both mRNA and protein levels. pGPx is expressed in various tissues in contact with body fluids, and detoxifies hydrogen peroxides and lipid hydroperoxides [19].
  • Our results suggest that the increased susceptibility of Gpx1-/- neurons to H2O2-induced apoptosis and neuronal cell death in vivo following cerebral ischaemia-reperfusion injury can be attributed in part to diminished activation of Akt [20].
  • These changes were associated with increased expression of the proinflammatory marker monocyte chemoattractant protein-1 in control mice but not in Gpx1-deficient mice [17].
  • Altogether, these results strongly suggest that the PEA3 factor might participate in the transcriptional control of the murine epididymis caput-specific gpx5 gene [18].
  • By using the same protocol, PAI-1 mRNA and protein levels were enhanced in GPX double-transgenic mice, and again this response was blunted by the addition of doxycycline [21].

Other interactions of Gpx1

  • To test this possible mechanism, we transfected human cytosolic GPX cDNA into human glioma cells overexpressing MnSOD [22].
  • Both catalase and glutathione peroxidase (GPx) activities were not markedly altered by MPTP in both systems [23].
  • Previously, we demonstrated that a perturbation in the Sod1-to-Gpx1 ratio, as a consequence of Sod1 overexpression, leads to senescence-like changes [16].
  • Nonsynonymous nucleotide polymorphisms were identified in all genes, except for Gpx1, Gpx3, and Gpx4 [24].
  • The results showed greater oxidative stress in SAMP8 than in SAMR1, largely because of a decrease in GSH levels and to an increase in GSSG and TBARS with the subsequent induction of the antioxidant enzymes GPX and GR [25].

Analytical, diagnostic and therapeutic context of Gpx1

  • Using a reverse transcription coupled to PCR amplification strategy, with degenerated primers localized in highly conserved domains of known glutathione peroxidase (GPX) proteins, we have generated, from mouse epididymal RNA, a cDNA fragment which was subsequently used to isolate a genomic clone encoding mouse plasma GPX (GPX3) [26].
  • Overall, the relative expression of ADH and Zn-Cu SOD were higher in treatment groups than in positive controls; whereas, the relative expression of GPX5 was higher in positive control groups than in treatment groups [27].
  • 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 [28].
  • Oral administration of Brahma Rasayana BR-50 mg/dose/mouse for 10 days and 30 days significantly enhanced the tissue levels of SOD, CAT, GST, GPX, serum and tissue GSH and significantly reduced the serum and tissue lipid peroxidation [29].
  • 5. In situ hybridization indicated expression of GPx4 isoforms in all developing germ layers during gastrulation and in the somite stage in the developing central nervous system and in the heart [30].


  1. Mutation accumulation in the intestine and colon of mice deficient in two intracellular glutathione peroxidases. Lee, D.H., Esworthy, R.S., Chu, C., Pfeifer, G.P., Chu, F.F. Cancer Res. (2006) [Pubmed]
  2. Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Chu, F.F., Esworthy, R.S., Chu, P.G., Longmate, J.A., Huycke, M.M., Wilczynski, S., Doroshow, J.H. Cancer Res. (2004) [Pubmed]
  3. Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. de Haan, J.B., Bladier, C., Griffiths, P., Kelner, M., O'Shea, R.D., Cheung, N.S., Bronson, R.T., Silvestro, M.J., Wild, S., Zheng, S.S., Beart, P.M., Hertzog, P.J., Kola, I. J. Biol. Chem. (1998) [Pubmed]
  4. Increased formation of reactive oxygen species, but no changes in glutathione peroxidase activity, in striata of mice transgenic for the Huntington's disease mutation. Pérez-Severiano, F., Santamaría, A., Pedraza-Chaverri, J., Medina-Campos, O.N., Ríos, C., Segovia, J. Neurochem. Res. (2004) [Pubmed]
  5. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Hockenbery, D.M., Oltvai, Z.N., Yin, X.M., Milliman, C.L., Korsmeyer, S.J. Cell (1993) [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. Mode of action of selenium inhibition of 7,12-dimethylbenz[a]anthracene-induced mouse mammary tumorigenesis. Lane, H.W., Medina, D. J. Natl. Cancer Inst. (1985) [Pubmed]
  8. Antioxidant enzyme response to hypericin in EMT6 mouse mammary carcinoma cells. Johnson, S.A., Pardini, R.S. Free Radic. Biol. Med. (1998) [Pubmed]
  9. Low levels of glutathione peroxidase 1 activity in selenium-deficient mouse liver affect c-Jun N-terminal kinase activation and p53 phosphorylation on Ser-15 in pro-oxidant-induced aponecrosis. Cheng, W.H., Zheng, X., Quimby, F.R., Roneker, C.A., Lei, X.G. Biochem. J. (2003) [Pubmed]
  10. Kidney expression of glutathione peroxidase-1 is not protective against streptozotocin-induced diabetic nephropathy. de Haan, J.B., Stefanovic, N., Nikolic-Paterson, D., Scurr, L.L., Croft, K.D., Mori, T.A., Hertzog, P., Kola, I., Atkins, R.C., Tesch, G.H. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  11. Glutathione peroxidase 1 and glutathione are required to protect mouse astrocytes from iron-mediated hydrogen peroxide toxicity. Liddell, J.R., Hoepken, H.H., Crack, P.J., Robinson, S.R., Dringen, R. J. Neurosci. Res. (2006) [Pubmed]
  12. Cellular glutathione peroxidase knockout mice express normal levels of selenium-dependent plasma and phospholipid hydroperoxide glutathione peroxidases in various tissues. Cheng, W.H., Ho, Y.S., Ross, D.A., Valentine, B.A., Combs, G.F., Lei, X.G. J. Nutr. (1997) [Pubmed]
  13. Akt phosphorylation and NFkappaB activation are counterregulated under conditions of oxidative stress. Taylor, J.M., Crack, P.J., Gould, J.A., Ali, U., Hertzog, P.J., Iannello, R.C. Exp. Cell Res. (2004) [Pubmed]
  14. Multiple deficiencies in antioxidant enzymes in mice result in a compound increase in sensitivity to oxidative stress. Van Remmen, H., Qi, W., Sabia, M., Freeman, G., Estlack, L., Yang, H., Mao Guo, Z., Huang, T.T., Strong, R., Lee, S., Epstein, C.J., Richardson, A. Free Radic. Biol. Med. (2004) [Pubmed]
  15. Mitochondrial oxidative stress in mice lacking the glutathione peroxidase-1 gene. Esposito, L.A., Kokoszka, J.E., Waymire, K.G., Cottrell, B., MacGregor, G.R., Wallace, D.C. Free Radic. Biol. Med. (2000) [Pubmed]
  16. Fibroblasts derived from Gpx1 knockout mice display senescent-like features and are susceptible to H2O2-mediated cell death. de Haan, J.B., Bladier, C., Lotfi-Miri, M., Taylor, J., Hutchinson, P., Crack, P.J., Hertzog, P., Kola, I. Free Radic. Biol. Med. (2004) [Pubmed]
  17. Lack of the antioxidant glutathione peroxidase-1 does not increase atherosclerosis in C57BL/J6 mice fed a high-fat diet. de Haan, J.B., Witting, P.K., Stefanovic, N., Pete, J., Daskalakis, M., Kola, I., Stocker, R., Smolich, J.J. J. Lipid Res. (2006) [Pubmed]
  18. The PEA3 protein of the Ets oncogene family is a putative transcriptional modulator of the mouse epididymis-specific glutathione peroxidase gene gpx5. Drevet, J.R., Lareyre, J.J., Schwaab, V., Vernet, P., Dufaure, J.P. Mol. Reprod. Dev. (1998) [Pubmed]
  19. Enhanced expression of plasma glutathione peroxidase in the thymus of mice treated with TCDD and its implication for TCDD-induced thymic atrophy. Cho, H.J., Hahn, E.J., Hwang, J.A., Hong, M.S., Kim, S.K., Pak, H.R., Park, J.H. Mol. Cells (2006) [Pubmed]
  20. Diminished Akt phosphorylation in neurons lacking glutathione peroxidase-1 (Gpx1) leads to increased susceptibility to oxidative stress-induced cell death. Taylor, J.M., Ali, U., Iannello, R.C., Hertzog, P., Crack, P.J. J. Neurochem. (2005) [Pubmed]
  21. Enhanced plasminogen activator inhibitor-1 expression in transgenic mice with hepatocyte-specific overexpression of superoxide dismutase or glutathione peroxidase. Franke, K., Curth, K., Lenart, J., Knochenhauer, D., Kietzmann, T. Antioxid. Redox Signal. (2004) [Pubmed]
  22. The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase. Li, S., Yan, T., Yang, J.Q., Oberley, T.D., Oberley, L.W. Cancer Res. (2000) [Pubmed]
  23. MPTP produces differential oxidative stress and antioxidative responses in the nigrostriatal and mesolimbic dopaminergic pathways. Hung, H.C., Lee, E.H. Free Radic. Biol. Med. (1998) [Pubmed]
  24. Spontaneous hypomorphic mutations in antioxidant enzymes of mice. Guo, Z., Higuchi, K., Mori, M. Free Radic. Biol. Med. (2003) [Pubmed]
  25. 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]
  26. Cloning of the mouse gene encoding plasma glutathione peroxidase: organization, sequence and chromosomal localization. Schwaab, V., Baud, E., Ghyselinck, N., Mattei, M.G., Dufaure, J.P., Drevet, J.R. Gene (1995) [Pubmed]
  27. Effect of Evodiae fructus extracts on gene expressions related with alcohol metabolism and antioxidation in ethanol-loaded mice. Cho, M.H., Shim, S.M., Lee, S.R., Mar, W., Kim, G.H. Food Chem. Toxicol. (2005) [Pubmed]
  28. 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]
  29. Effect of Brahma Rasayana on antioxidant systems and cytokine levels in mice during cyclophosphamide administration. Rekha, P.S., Kuttan, G., Kuttan, R. J. Exp. Clin. Cancer Res. (2001) [Pubmed]
  30. The role of phospholipid hydroperoxide glutathione peroxidase isoforms in murine embryogenesis. Borchert, A., Wang, C.C., Ufer, C., Schiebel, H., Savaskan, N.E., Kuhn, H. J. Biol. Chem. (2006) [Pubmed]
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