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Gene Review

Gpx4  -  glutathione peroxidase 4

Mus musculus

Synonyms: GPx-4, GSHPx-4, Glutathione peroxidase 4, PHGPx, Phospholipid hydroperoxide glutathione peroxidase, mitochondrial, ...
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Disease relevance of Gpx4


High impact information on Gpx4


Chemical compound and disease context of Gpx4


Biological context of Gpx4

  • These data demonstrate that Gpx4 plays a role in vivo in the mechanism of apoptosis induced by oxidative stress that most likely occurs through oxidative damage to mitochondrial phospholipids such as cardiolipin [9].
  • The human GPX4 transgene rescued the lethal phenotype of null mutation of the mouse Gpx4 gene, indicating that the transgene can replace the essential role of mouse Gpx4 in mouse development [9].
  • Interestingly, cell lines derived from Gpx4(+/-) mice are markedly sensitive to inducers of oxidative stress, including gamma-irradiation, paraquat, tert-butylhydroperoxide, and hydrogen peroxide, as compared to cell lines derived from wild-type control littermates [10].
  • Even more inhibition of glutathione peroxidase activity leads to cell death in the digits, suggesting that a decrease in antioxidant activity, likely due to Gpx4, caused an increase in ROS levels, thus triggering apoptosis [11].
  • When cultured at low cell density, MEFs from Gpx4(+/-) mice also showed retarded growth under normal culture conditions (20% oxygen) that was reversed by culturing under low oxygen (2% oxygen) [12].

Anatomical context of Gpx4


Associations of Gpx4 with chemical compounds


Other interactions of Gpx4


Analytical, diagnostic and therapeutic context of Gpx4

  • A total of 32 gpx4 hemizygous (GPx4+/-) and wild-type (WT) mice (8- to 10-weeks old; 16 males and 16 females) were fed a selenium-adequate diet and given an intraperitoneal injection of paraquat (PQ; 24 mg/kg body wt) or phosphate-buffered saline (PBS) [21].
  • Northern blotting performed with a cDNA specific for the longer PHGPx transcript demonstrated that this longer PHGPx transcript was present only in the testis [22].
  • The activity of purified testicular PHGPX on several photochemically-generated cholesterol hydroperoxide (ChOOH) species was investigated, using high-performance liquid chromatography with electrochemical detection for peroxide analysis and thinlayer chromatography with 14C-radiodetection for diol product analysis [23].
  • By semi-quantitative RT-PCR analysis we observed that the cytosolic form of PHGPx was present in embryonic and somatic tissues whereas the mitochondrial and nuclear forms were detectable only in testicular tissue [24].


  1. Glutathione peroxidase 4 protects cortical neurons from oxidative injury and amyloid toxicity. Ran, Q., Gu, M., Van Remmen, H., Strong, R., Roberts, J.L., Richardson, A. J. Neurosci. Res. (2006) [Pubmed]
  2. Identification of a novel putative non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) essential for alleviating oxidative stress generated from polyunsaturated fatty acids in breast cancer cells. Utomo, A., Jiang, X., Furuta, S., Yun, J., Levin, D.S., Wang, Y.C., Desai, K.V., Green, J.E., Chen, P.L., Lee, W.H. J. Biol. Chem. (2004) [Pubmed]
  3. Essential role of the apolipoprotein E receptor-2 in sperm development. Andersen, O.M., Yeung, C.H., Vorum, H., Wellner, M., Andreassen, T.K., Erdmann, B., Mueller, E.C., Herz, J., Otto, A., Cooper, T.G., Willnow, T.E. J. Biol. Chem. (2003) [Pubmed]
  4. Suppression of the malignant phenotype in pancreatic cancer by overexpression of phospholipid hydroperoxide glutathione peroxidase. Liu, J., Du, J., Zhang, Y., Sun, W., Smith, B.J., Oberley, L.W., Cullen, J.J. Hum. Gene Ther. (2006) [Pubmed]
  5. Blocking tumor cell eicosanoid synthesis by GP x 4 impedes tumor growth and malignancy. Heirman, I., Ginneberge, D., Brigelius-Flohé, R., Hendrickx, N., Agostinis, P., Brouckaert, P., Rottiers, P., Grooten, J. Free Radic. Biol. Med. (2006) [Pubmed]
  6. The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a protein thiol peroxidase contributing to sperm chromatin stability. Conrad, M., Moreno, S.G., Sinowatz, F., Ursini, F., Kölle, S., Roveri, A., Brielmeier, M., Wurst, W., Maiorino, M., Bornkamm, G.W. Mol. Cell. Biol. (2005) [Pubmed]
  7. Inverse regulation of lipid-peroxidizing and hydroperoxyl lipid-reducing enzymes by interleukins 4 and 13. Schnurr, K., Borchert, A., Kuhn, H. FASEB J. (1999) [Pubmed]
  8. Polysome distribution of phospholipid hydroperoxide glutathione peroxidase mRNA: evidence for a block in elongation at the UGA/selenocysteine codon. Fletcher, J.E., Copeland, P.R., Driscoll, D.M. RNA (2000) [Pubmed]
  9. Transgenic mice overexpressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis. Ran, Q., Liang, H., Gu, M., Qi, W., Walter, C.A., Roberts, L.J., Herman, B., Richardson, A., Van Remmen, H. J. Biol. Chem. (2004) [Pubmed]
  10. The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Yant, L.J., Ran, Q., Rao, L., Van Remmen, H., Shibatani, T., Belter, J.G., Motta, L., Richardson, A., Prolla, T.A. Free Radic. Biol. Med. (2003) [Pubmed]
  11. Expression and regulation of antioxidant enzymes in the developing limb support a function of ROS in interdigital cell death. Schnabel, D., Salas-Vidal, E., Narváez, V., Sánchez-Carbente, M.d.e.l. .R., Hernández-García, D., Cuervo, R., Covarrubias, L. Dev. Biol. (2006) [Pubmed]
  12. Embryonic fibroblasts from Gpx4+/- mice: a novel model for studying the role of membrane peroxidation in biological processes. Ran, Q., Van Remmen, H., Gu, M., Qi, W., Roberts, L.J., Prolla, T., Richardson, A. Free Radic. Biol. Med. (2003) [Pubmed]
  13. Nonsense-mediated decay of mRNA for the selenoprotein phospholipid hydroperoxide glutathione peroxidase is detectable in cultured cells but masked or inhibited in rat tissues. Sun, X., Li, X., Moriarty, P.M., Henics, T., LaDuca, J.P., Maquat, L.E. Mol. Biol. Cell (2001) [Pubmed]
  14. Regulation of expression of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase gene. Tissue-specific expression pattern and identification of functional cis- and trans-regulatory elements. Borchert, A., Savaskan, N.E., Kuhn, H. J. Biol. Chem. (2003) [Pubmed]
  15. Hyperexpression of catalase in selenium-deprived murine L1210 cells. Lin, F., Thomas, J.P., Girotti, A.W. Arch. Biochem. Biophys. (1993) [Pubmed]
  16. Protective and determining factors for the overall lipid peroxidation in ultraviolet A1-irradiated fibroblasts: in vitro and in vivo investigations. Dissemond, J., Schneider, L.A., Brenneisen, P., Briviba, K., Wenk, J., Wlaschek, M., Scharffetter-Kochanek, K. Br. J. Dermatol. (2003) [Pubmed]
  17. Noxious effects of oxygen reactive species on energy-coupling processes in Ehrlich ascites tumor mitochondria and the protection by pantothenic acid. Slyshenkov, V.S., Moiseenok, A.G., Wojtczak, L. Free Radic. Biol. Med. (1996) [Pubmed]
  18. Spontaneous hypomorphic mutations in antioxidant enzymes of mice. Guo, Z., Higuchi, K., Mori, M. Free Radic. Biol. Med. (2003) [Pubmed]
  19. Molecular cloning and functional expression of nucleolar phospholipid hydroperoxide glutathione peroxidase in mammalian cells. Nakamura, T., Imai, H., Tsunashima, N., Nakagawa, Y. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  20. Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene. Imai, H., Hirao, F., Sakamoto, T., Sekine, K., Mizukura, Y., Saito, M., Kitamoto, T., Hayasaka, M., Hanaoka, K., Nakagawa, Y. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  21. Effects of gpx4 haploid insufficiency on GPx4 activity, selenium concentration, and paraquat-induced protein oxidation in murine tissues. Scimeca, M.S., Lisk, D.J., Prolla, T., Lei, X.G. Exp. Biol. Med. (Maywood) (2005) [Pubmed]
  22. Murine phospholipid hydroperoxide glutathione peroxidase: cDNA sequence, tissue expression, and mapping. Knopp, E.A., Arndt, T.L., Eng, K.L., Caldwell, M., LeBoeuf, R.C., Deeb, S.S., O'Brien, K.D. Mamm. Genome (1999) [Pubmed]
  23. Enzymatic reducibility in relation to cytotoxicity for various cholesterol hydroperoxides. Korytowski, W., Geiger, P.G., Girotti, A.W. Biochemistry (1996) [Pubmed]
  24. Embryonic expression profile of phospholipid hydroperoxide glutathione peroxidase. Schneider, M., Vogt Weisenhorn, D.M., Seiler, A., Bornkamm, G.W., Brielmeier, M., Conrad, M. Gene Expr. Patterns (2006) [Pubmed]
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