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Gene Review

GPX1  -  glutathione peroxidase 1

Homo sapiens

Synonyms: Cellular glutathione peroxidase, GPXD, GPx-1, GSHPX1, GSHPx-1, ...
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Disease relevance of GPX1

  • The GPX1 variants have not been studied with respect to breast cancer, but Pro198Leu has been associated with lung cancer [1].
  • Despite its largely referenced beneficial effects for cells, GSH was toxic for ECV304 cells in a dose-dependent manner but GSH-induced toxicity was reduced in selenium supplemented cultures and completely abolished in ECV304 overexpressing GPX1, compared to control [2].
  • We found no significant association between the GPX1 genotypes and prostate cancer [3].
  • DESIGN AND METHODS: Data from two population-based, case-control studies of lymphoma in the UK (700 cases and 915 controls) and USA (1593 cases and 2517 controls) were pooled to analyze polymorphisms in genes involved in the oxidative stress response (SOD2 Val16Ala, CAT C-262T and GPX1 Pro197Leu) [4].
  • The GPX1 197Leu allele was weakly associated with NHL and follicular lymphoma [4].

Psychiatry related information on GPX1


High impact information on GPX1


Chemical compound and disease context of GPX1


Biological context of GPX1

  • Low yield of polymorphisms from EST blast searching: analysis of genes related to oxidative stress and verification of the P197L polymorphism in GPX1 [19].
  • However, in men with at least 1 Ala MnSOD allele the risk associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to 31.24, p = 0.024) [20].
  • In situ hybridization localized the human GPX1 gene to a single site on chromosome 3, at region 3q11-13 [21].
  • 1. Thus, three genomic sites bear sequence homology to the GPX1 cDNA, and the one most homologous maps to 3q11-13.1 [21].
  • As GPX1 overexpression could drain the cellular reduced glutathione (GSH) pool, we also tested the effects of extracellular GSH supplementation on cell growth [2].

Anatomical context of GPX1


Associations of GPX1 with chemical compounds

  • The 26- and 21-kDa proteins were identified in immunoblot assays as the glutathione peroxidase (cGPX or GPX1) subunit and phospholipid hydroperoxide glutathione peroxidase (PHGPX or GPX4), respectively [26].
  • Our results indicate selective induction of the GPX1 gene by BLM and different redox responses to BLM between WI38 and VA13 cells [27].
  • GPX1 protein and activity level was not consistently detectable in H1703 cells, with or without Se supplementation; its mRNA was present but very low [28].
  • During thyroid hormone synthesis GPX1, GPX3 and TR1 are up-regulated, providing the thyrocytes with considerable protection from peroxidative damage [29].
  • The biological roles of the essential micronutrient Se are attributed to its presence in a range of 20-30 selenoproteins including the cytosolic and phospholipid hydroperoxide glutathione peroxidases (GPX1 and GPX4) [30].
  • Glutathione peroxidase-1 (GPx-1), a selenocysteine-containing antioxidant enzyme, may be a key target of Hcy's deleterious actions, and several experimental and clinical studies have demonstrated a complex relationship between plasma total homocysteine (tHcy), GPx-1, and endothelial dysfunction [31].

Physical interactions of GPX1


Enzymatic interactions of GPX1

  • The rate of 14CO2 evolution, when the cells were subsequently incubated with 14C-labeled glucose, provided a measure of the rate at which NADPH was being oxidized by the glutathione peroxidase/reductase system for the disposal of H2O2 [37].
  • G-6-PD-deficiency is a genetic disorder of erythrocytes in which the inability of affected cells to maintain NAD(P)H levels sufficient for the reduction of oxidized glutathione results in inadequate detoxification of hydrogen peroxide through glutathione peroxidase [38].

Regulatory relationships of GPX1


Other interactions of GPX1

  • Even at very low H2O2 concentrations GPO reaches only approximately 8% of the rate at which catalase simultaneously degrades H2O2 [44].
  • Levels of GSTP1, GSTM3, and GSHPx were significantly (P < 0.05) lower in NBECs from subjects with bronchogenic carcinoma [15].
  • Both observations weaken the proposed inverse correlation between ER status and GPX-1 production [25].
  • Further, the gene expression index formed by multiplying the values for mGST x GSTM3 x GSHPx x GSHPxA x GSTP1 had a sensitivity (90%) and specificity (76%) for detecting NBECs from bronchogenic carcinoma subjects that was better than any individual gene [15].
  • Under HG, there was a twofold increase in the expression of CAT, CuZnSOD, and GPX mRNA in the patients without complications and the control subjects versus patients with nephropathy (P < 0.0001), and MnSOD did not change in any of the groups [45].

Analytical, diagnostic and therapeutic context of GPX1

  • Northern blot analysis indicated that the increase in GPX activities was due to increased transcript levels of GPX1 but not GPX4 in both cells [27].
  • RESULTS: There was a significant difference in GPX1 genotype frequency between the case and control groups (p = 0.001) [20].
  • Southern blot analysis of human genomic DNA with the GPX1 cDNA showed that restriction endonucleases without sites in the probe sequence produced three hybridizing bands at standard stringency, diminishing to one strongly and one weakly hybridizing band at high stringency [21].
  • ECV304 were stably transfected with the GPX1 cDNA and used for quantification of Bax (pro-apoptotic) and Bcl-2 (antiapoptotic) mRNA and protein levels, by quantitative RT-PCR and Western-blot [46].
  • Utilizing simulated data in the context of two genomic regions GPX1 and GPX3, we evaluate the validity of the proposed test for small sample sizes and study its power in the presence and absence of missing genotype data [47].


  1. Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry. Knight, J.A., Onay, U.V., Wells, S., Li, H., Shi, E.J., Andrulis, I.L., Ozcelik, H. Cancer Epidemiol. Biomarkers Prev. (2004) [Pubmed]
  2. Overexpression of cytosolic glutathione peroxidase (GPX1) delays endothelial cell growth and increases resistance to toxic challenges. Faucher, K., Rabinovitch-Chable, H., Barrière, G., Cook-Moreau, J., Rigaud, M. Biochimie (2003) [Pubmed]
  3. Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer. Kote-Jarai, Z., Durocher, F., Edwards, S.M., Hamoudi, R., Jackson, R.A., Ardern-Jones, A., Murkin, A., Dearnaley, D.P., Kirby, R., Houlston, R., Easton, D.F., Eeles, R. Prostate Cancer Prostatic Dis. (2002) [Pubmed]
  4. Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin's lymphoma. Lightfoot, T.J., Skibola, C.F., Smith, A.G., Forrest, M.S., Adamson, P.J., Morgan, G.J., Bracci, P.M., Roman, E., Smith, M.T., Holly, E.A. Haematologica (2006) [Pubmed]
  5. Antioxidant enzymes and lipid peroxides in children with cerebral palsy. Kulak, W., Sobaniec, W., Solowej, E., Sobaniec, H. Life Sci. (2005) [Pubmed]
  6. Regional brain activity of free radical defense enzymes in autopsy samples from patients with Alzheimer's disease and from nondemented controls. Chen, L., Richardson, J.S., Caldwell, J.E., Ang, L.C. Int. J. Neurosci. (1994) [Pubmed]
  7. Catalase, superoxide dismutase and glutathione peroxidase activities of lung and liver during human development. McElroy, M.C., Postle, A.D., Kelly, F.J. Biochim. Biophys. Acta (1992) [Pubmed]
  8. Oxygen free radicals and myocardial damage: protective role of thiol-containing agents. Ferrari, R., Ceconi, C., Curello, S., Cargnoni, A., Alfieri, O., Pardini, A., Marzollo, P., Visioli, O. Am. J. Med. (1991) [Pubmed]
  9. The effect of sulfur dioxide inhalation on active avoidance learning, antioxidant status and lipid peroxidation during aging. Yargicoglu, P., Sahin, E., Gümüşlü, S., Ağar, A. Neurotoxicology and teratology (2007) [Pubmed]
  10. Ultraviolet-induced cell death blocked by a selenoprotein from a human dermatotropic poxvirus. Shisler, J.L., Senkevich, T.G., Berry, M.J., Moss, B. Science (1998) [Pubmed]
  11. Genome sequence of a human tumorigenic poxvirus: prediction of specific host response-evasion genes. Senkevich, T.G., Bugert, J.J., Sisler, J.R., Koonin, E.V., Darai, G., Moss, B. Science (1996) [Pubmed]
  12. Ovothiol replaces glutathione peroxidase as a hydrogen peroxide scavenger in sea urchin eggs. Turner, E., Hager, L.J., Shapiro, B.M. Science (1988) [Pubmed]
  13. Erythrocyte glutathione peroxidase and myocardial infarction. Gromadzińska, J., Skłodowska, M. JAMA (1990) [Pubmed]
  14. Decreased selenium levels in acute myocardial infarction. Kok, F.J., Hofman, A., Witteman, J.C., de Bruijn, A.M., Kruyssen, D.H., de Bruin, M., Valkenburg, H.A. JAMA (1989) [Pubmed]
  15. Normal bronchial epithelial cell expression of glutathione transferase P1, glutathione transferase M3, and glutathione peroxidase is low in subjects with bronchogenic carcinoma. Crawford, E.L., Khuder, S.A., Durham, S.J., Frampton, M., Utell, M., Thilly, W.G., Weaver, D.A., Ferencak, W.J., Jennings, C.A., Hammersley, J.R., Olson, D.A., Willey, J.C. Cancer Res. (2000) [Pubmed]
  16. Glutathione peroxidase-1 overexpression prevents ceramide production and partially inhibits apoptosis in doxorubicin-treated human breast carcinoma cells. Gouazé, V., Mirault, M.E., Carpentier, S., Salvayre, R., Levade, T., Andrieu-Abadie, N. Mol. Pharmacol. (2001) [Pubmed]
  17. Effects of irbesartan on intracellular antioxidant enzyme expression and activity in adolescents and young adults with early diabetic angiopathy. Chiarelli, F., Di Marzio, D., Santilli, F., Mohn, A., Blasetti, A., Cipollone, F., Mezzetti, A., Verrotti, A. Diabetes Care (2005) [Pubmed]
  18. Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3. Suzuki, K., Koike, H., Matsui, H., Ono, Y., Hasumi, M., Nakazato, H., Okugi, H., Sekine, Y., Oki, K., Ito, K., Yamamoto, T., Fukabori, Y., Kurokawa, K., Yamanaka, H. Int. J. Cancer (2002) [Pubmed]
  19. Low yield of polymorphisms from EST blast searching: analysis of genes related to oxidative stress and verification of the P197L polymorphism in GPX1. Forsberg, L., de Faire, U., Morgenstern, R. Hum. Mutat. (1999) [Pubmed]
  20. Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant. Ichimura, Y., Habuchi, T., Tsuchiya, N., Wang, L., Oyama, C., Sato, K., Nishiyama, H., Ogawa, O., Kato, T. J. Urol. (2004) [Pubmed]
  21. Isolation and chromosomal localization of the human glutathione peroxidase gene. Chada, S., Le Beau, M.M., Casey, L., Newburger, P.E. Genomics (1990) [Pubmed]
  22. Assignment of the ARHA and GPX1 genes to human chromosome bands 3p21.3 by in situ hybridization and with somatic cell hybrids. Kiss, C., Li, J., Szeles, A., Gizatullin, R.Z., Kashuba, V.I., Lushnikova, T., Protopopov, A.I., Kelve, M., Kiss, H., Kholodnyuk, I.D., Imreh, S., Klein, G., Zabarovsky, E.R. Cytogenet. Cell Genet. (1997) [Pubmed]
  23. Genotype-activity relationship for Mn-superoxide dismutase, glutathione peroxidase 1 and catalase in humans. Bastaki, M., Huen, K., Manzanillo, P., Chande, N., Chen, C., Balmes, J.R., Tager, I.B., Holland, N. Pharmacogenet. Genomics (2006) [Pubmed]
  24. Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway. Jing, Y., Dai, J., Chalmers-Redman, R.M., Tatton, W.G., Waxman, S. Blood (1999) [Pubmed]
  25. Expression of selenium-dependent glutathione peroxidase in human breast tumor cell lines. Esworthy, R.S., Baker, M.A., Chu, F.F. Cancer Res. (1995) [Pubmed]
  26. Levels of major selenoproteins in T cells decrease during HIV infection and low molecular mass selenium compounds increase. Gladyshev, V.N., Stadtman, T.C., Hatfield, D.L., Jeang, K.T. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  27. Levels of reactive oxygen species and primary antioxidant enzymes in WI38 versus transformed WI38 cells following bleomcyin treatment. Yen, H.C., Chang, H.M., Majima, H.J., Chen, F.Y., Li, S.H. Free Radic. Biol. Med. (2005) [Pubmed]
  28. Effects of selenium supplementation on expression of glutathione peroxidase isoforms in cultured human lung adenocarcinoma cell lines. Romanowska, M., Kikawa, K.D., Fields, J.R., Maciag, A., North, S.L., Shiao, Y.H., Kasprzak, K.S., Anderson, L.M. Lung Cancer (2007) [Pubmed]
  29. Selenium and endocrine systems. Beckett, G.J., Arthur, J.R. J. Endocrinol. (2005) [Pubmed]
  30. A novel single nucleotide polymorphism in the 3' untranslated region of human glutathione peroxidase 4 influences lipoxygenase metabolism. Villette, S., Kyle, J.A., Brown, K.M., Pickard, K., Milne, J.S., Nicol, F., Arthur, J.R., Hesketh, J.E. Blood Cells Mol. Dis. (2002) [Pubmed]
  31. Homocysteine and glutathione peroxidase-1. Lubos, E., Loscalzo, J., Handy, D.E. Antioxid. Redox Signal. (2007) [Pubmed]
  32. Sudden infant death syndrome: oxidative stress. Reid, G.M., Tervit, H. Med. Hypotheses (1999) [Pubmed]
  33. p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis. Hussain, S.P., Amstad, P., He, P., Robles, A., Lupold, S., Kaneko, I., Ichimiya, M., Sengupta, S., Mechanic, L., Okamura, S., Hofseth, L.J., Moake, M., Nagashima, M., Forrester, K.S., Harris, C.C. Cancer Res. (2004) [Pubmed]
  34. Identification and molecular cloning of a human selenocysteine insertion sequence-binding protein. A bifunctional role for DNA-binding protein B. Shen, Q., Wu, R., Leonard, J.L., Newburger, P.E. J. Biol. Chem. (1998) [Pubmed]
  35. Retinal pigment epithelium pigment granules stimulate the photo-oxidation of unsaturated fatty acids. Dontsov, A.E., Glickman, R.D., Ostrovsky, M.A. Free Radic. Biol. Med. (1999) [Pubmed]
  36. Recognition and binding of the human selenocysteine insertion sequence by nucleolin. Wu, R., Shen, Q., Newburger, P.E. J. Cell. Biochem. (2000) [Pubmed]
  37. Importance of catalase in the disposal of hydrogen peroxide within human erythrocytes. Gaetani, G.F., Kirkman, H.N., Mangerini, R., Ferraris, A.M. Blood (1994) [Pubmed]
  38. Perspectives on hydrogen peroxide and drug-induced hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency. Hochstein, P. Free Radic. Biol. Med. (1988) [Pubmed]
  39. Endogenous production of reactive oxygen species is required for stimulation of human articular chondrocyte matrix metalloproteinase production by fibronectin fragments. Del Carlo, M., Schwartz, D., Erickson, E.A., Loeser, R.F. Free Radic. Biol. Med. (2007) [Pubmed]
  40. PU.1 regulates glutathione peroxidase expression in neutrophils. Throm, S.L., Klemsz, M.J. J. Leukoc. Biol. (2003) [Pubmed]
  41. N-acetylcysteine attenuates TNF-alpha-induced human vascular endothelial cell apoptosis and restores eNOS expression. Xia, Z., Liu, M., Wu, Y., Sharma, V., Luo, T., Ouyang, J., McNeill, J.H. Eur. J. Pharmacol. (2006) [Pubmed]
  42. Novel human ocular glutathione S-transferases with high activity toward 4-hydroxynonenal. Singhal, S.S., Awasthi, S., Srivastava, S.K., Zimniak, P., Ansari, N.H., Awasthi, Y.C. Invest. Ophthalmol. Vis. Sci. (1995) [Pubmed]
  43. Oxidized low-density lipoprotein induces the production of interleukin-8 by endothelial cells. Claise, C., Edeas, M., Chalas, J., Cockx, A., Abella, A., Capel, L., Lindenbaum, A. FEBS Lett. (1996) [Pubmed]
  44. Direct evidence for catalase as the predominant H2O2 -removing enzyme in human erythrocytes. Mueller, S., Riedel, H.D., Stremmel, W. Blood (1997) [Pubmed]
  45. The response of antioxidant genes to hyperglycemia is abnormal in patients with type 1 diabetes and diabetic nephropathy. Hodgkinson, A.D., Bartlett, T., Oates, P.J., Millward, B.A., Demaine, A.G. Diabetes (2003) [Pubmed]
  46. Overexpression of human GPX1 modifies Bax to Bcl-2 apoptotic ratio in human endothelial cells. Faucher, K., Rabinovitch-Chable, H., Cook-Moreau, J., Barrière, G., Sturtz, F., Rigaud, M. Mol. Cell. Biochem. (2005) [Pubmed]
  47. A haplotype-based test of association using data from cohort and nested case-control epidemiologic studies. Chen, J., Peters, U., Foster, C., Chatterjee, N. Hum. Hered. (2004) [Pubmed]
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