phospholipid hydroperoxide glutathione peroxidase


Gene Symbol: phospholipid hydroperoxide glutathione peroxidase
Description: glutathione peroxidase 4
Alias: Gshpx-4, Phgpx, gpx-4, snGpx, phospholipid hydroperoxide glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, mitochondrial, phospholipid hydroperoxide glutathione peroxidase, nuclear
Species: rat

Top Publications

  1. Orian L, Mauri P, Roveri A, Toppo S, Benazzi L, Bosello Travain V, et al. Selenocysteine oxidation in glutathione peroxidase catalysis: an MS-supported quantum mechanics study. Free Radic Biol Med. 2015;87:1-14 pubmed publisher
    ..The selenenylamide bypass prevents destruction of the redox center due to over-oxidation of the selenium or its elimination and likely allows fine-tuning of GPx activity or alternate substrate reactions for regulatory purposes. ..
  2. Hauser D, Dukes A, Mortimer A, Hastings T. Dopamine quinone modifies and decreases the abundance of the mitochondrial selenoprotein glutathione peroxidase 4. Free Radic Biol Med. 2013;65:419-427 pubmed publisher
    ..Our findings suggest that a decrease in mitochondrial GPx4 monomer and a functional loss of activity may be a contributing factor to the vulnerability of dopaminergic neurons in Parkinson's disease. ..
  3. Arai M, Imai H, Sumi D, Imanaka T, Takano T, Chiba N, et al. Import into mitochondria of phospholipid hydroperoxide glutathione peroxidase requires a leader sequence. Biochem Biophys Res Commun. 1996;227:433-9 pubmed
    An in vitro import system was used to characterize the mechanism of import of phospholipid hydroperoxide glutathione peroxidase (PHGPx) into mitochondria...
  4. Zafiriou M, Deva R, Ciccoli R, Siafaka Kapadai A, Nigam S. Biological role of hepoxilins: upregulation of phospholipid hydroperoxide glutathione peroxidase as a cellular response to oxidative stress?. Prostaglandins Leukot Essent Fatty Acids. 2007;77:209-15 pubmed
    ..Here, we show that HXA3 at as low as 100 nM concentration upregulates phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA and protein expressions, whereas other metabolites of AA metabolism 12S-HpETE ..
  5. Savaskan N, Borchert A, Bräuer A, Kuhn H. Role for glutathione peroxidase-4 in brain development and neuronal apoptosis: specific induction of enzyme expression in reactive astrocytes following brain injury. Free Radic Biol Med. 2007;43:191-201 pubmed
    ..We hypothesize that astrocytic upregulation of GPx4 in response to injury is part of a protective cascade counteracting further cell damage. ..
  6. Weir C, Robaire B. Spermatozoa have decreased antioxidant enzymatic capacity and increased reactive oxygen species production during aging in the Brown Norway rat. J Androl. 2007;28:229-40 pubmed
    ..Taken together, these results suggest a decreased capacity for aged spermatozoa to handle oxidative stress and provide a potential basis for understanding the underlying cause of decreased quality of spermatozoa during aging. ..
  7. Haraguchi C, Mabuchi T, Hirata S, Shoda T, Yamada A, Hoshi K, et al. Spatiotemporal changes of levels of a moonlighting protein, phospholipid hydroperoxide glutathione peroxidase, in subcellular compartments during spermatogenesis in the rat testis. Biol Reprod. 2003;69:885-95 pubmed
    ..temporal changes in the subcellular localization and levels of a moonlighting protein, phospholipid hydroperoxide glutathione peroxidase (PHGPx), in spermatogenic cells and mature sperm of the rat by immunofluorescence and ..
  8. Arai M, Imai H, Koumura T, Yoshida M, Emoto K, Umeda M, et al. Mitochondrial phospholipid hydroperoxide glutathione peroxidase plays a major role in preventing oxidative injury to cells. J Biol Chem. 1999;274:4924-33 pubmed
    b>Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is synthesized as a long form (L-form; 23 kDa) and a short form (S-form; 20 kDa)...
  9. Ursini F, Heim S, Kiess M, Maiorino M, Roveri A, Wissing J, et al. Dual function of the selenoprotein PHGPx during sperm maturation. Science. 1999;285:1393-6 pubmed
    The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) changes its physical characteristics and biological functions during sperm maturation...

More Information


  1. 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
    ..TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system...
  2. Mitra K, Rangaraj N, Shivaji S. Novelty of the pyruvate metabolic enzyme dihydrolipoamide dehydrogenase in spermatozoa: correlation of its localization, tyrosine phosphorylation, and activity during sperm capacitation. J Biol Chem. 2005;280:25743-53 pubmed
  3. Hattori H, Imai H, Hanamoto A, Furuhama K, Nakagawa Y. Up-regulation of phospholipid hydroperoxide glutathione peroxidase in rat casein-induced polymorphonuclear neutrophils. Biochem J. 2005;389:279-87 pubmed
    ..In the present paper, we report on the regulation of expression of PHGPx (phospholipid hydroperoxide glutathione peroxidase) and cGPx (cytosolic glutathione peroxidase) in rat PMNs in the inflammation site...
  4. Maiorino M, Mauri P, Roveri A, Benazzi L, Toppo S, Bosello V, et al. Primary structure of the nuclear forms of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in rat spermatozoa. FEBS Lett. 2005;579:667-70 pubmed
    b>Phospholipid hydroperoxide glutathione peroxidase is a monomeric Se-peroxidase highly expressed in mammalian male germ cells...
  5. Pushpa Rekha T, Burdsall A, Oleksa L, Chisolm G, Driscoll D. Rat phospholipid-hydroperoxide glutathione peroxidase. cDNA cloning and identification of multiple transcription and translation start sites. J Biol Chem. 1995;270:26993-9 pubmed
    Phospholipid-hydroperoxide glutathione peroxidase (PhGPx) is a selenoenzyme that reduces hydroperoxides of phospholipid, cholesterol, and cholesteryl ester...
  6. Sunde R, Evenson J, Thompson K, Sachdev S. Dietary selenium requirements based on glutathione peroxidase-1 activity and mRNA levels and other Se-dependent parameters are not increased by pregnancy and lactation in rats. J Nutr. 2005;135:2144-50 pubmed
  7. Puglisi R, Tramer F, Panfili E, Micali F, Sandri G, Boitani C. Differential splicing of the phospholipid hydroperoxide glutathione peroxidase gene in diploid and haploid male germ cells in the rat. Biol Reprod. 2003;68:405-11 pubmed
    b>Phospholipid hydroperoxide glutathione peroxidase (PHGPx, 20 kDa) and sperm nuclei glutathione peroxidase (snGPx, 34 kDa) are two selenoproteins present in mammalian testis and epididymal spermatozoa...
  8. Hollander J, Lin K, Scott B, Dillmann W. Overexpression of PHGPx and HSP60/10 protects against ischemia/reoxygenation injury. Free Radic Biol Med. 2003;35:742-51 pubmed
    ..We examined the effects of mitochondrial phospholipid hydroperoxide glutathione peroxidase (mPHGPx) and cytosolic PHGPx (cPHGPx) overexpression on protection against simulated I/R in ..
  9. Roveri A, Casasco A, Maiorino M, Dalan P, Calligaro A, Ursini F. Phospholipid hydroperoxide glutathione peroxidase of rat testis. Gonadotropin dependence and immunocytochemical identification. J Biol Chem. 1992;267:6142-6 pubmed
    ..The attribution of this activity to the selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPX) was supported by cross-reactivity with antibodies raised against pig heart PHGPX ..
  10. Latrèche L, Duhieu S, Touat Hamici Z, Jean Jean O, Chavatte L. The differential expression of glutathione peroxidase 1 and 4 depends on the nature of the SECIS element. RNA Biol. 2012;9:681-90 pubmed publisher
    ..Finally, the profusion of selenium of the culture medium exacerbates the lack of factors involved in selenocysteine insertion. ..
  11. Maiorino M, Scapin M, Ursini F, Biasolo M, Bosello V, Flohe L. Distinct promoters determine alternative transcription of gpx-4 into phospholipid-hydroperoxide glutathione peroxidase variants. J Biol Chem. 2003;278:34286-90 pubmed
    A nuclear variant of phospholipid-hydroperoxide glutathione peroxidase (PHGPx, GPx-4) was considered to be derived from alternative pre-mRNA splicing in testis and to regulate sperm maturation...
  12. Yant L, Ran Q, Rao L, Van Remmen H, Shibatani T, Belter J, et al. The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic Biol Med. 2003;34:496-502 pubmed
    ..b>Phospholipid hydroperoxide glutathione peroxidase (GPX4) is the only major antioxidant enzyme known to directly reduce phospholipid ..
  13. Bertelsmann H, Behne D, Kyriakopoulos A. Studies with regard to the apoptosis of testicular germ cells in rats fed a diet enriched with polyunsaturated Fatty acids. Ann N Y Acad Sci. 2009;1171:372-6 pubmed publisher
    ..Male germ cells in the rat contain most of the testicular phospholipid hydroperoxide glutathione peroxidase (PHGPx), mainly as the mitochondrial isoform of this selenoprotein (m-PHGPx)...
  14. Sunde R, Thompson K. Dietary selenium requirements based on tissue selenium concentration and glutathione peroxidase activities in old female rats. J Trace Elem Med Biol. 2009;23:132-7 pubmed publisher
    ..Collectively, this indicates that the homeostatic mechanisms related to retention and maintenance of Se status are still fully functional in old female rats. ..
  15. Zhang L, Fujii S, Kosaka H. Effect of oestrogen on reactive oxygen species production in the aortas of ovariectomized Dahl salt-sensitive rats. J Hypertens. 2007;25:407-14 pubmed
    ..Oestrogen supplementation counteracted these alterations, showing how oestrogen is antioxidative. ..
  16. Scheerer P, Borchert A, Krauss N, Wessner H, Gerth C, Hohne W, et al. Structural basis for catalytic activity and enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4 (GPx4). Biochemistry. 2007;46:9041-9 pubmed
    b>Phospholipid hydroperoxide glutathione peroxidase (GPx4) is a moonlighting selenoprotein, which has been implicated in anti-oxidative defense, sperm development, and cerebral embryogenesis...
  17. Tramer F, Micali F, Sandri G, Bertoni A, Lenzi A, Gandini L, et al. Enzymatic and immunochemical evaluation of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in testes and epididymal spermatozoa of rats of different ages. Int J Androl. 2002;25:72-83 pubmed
    ..b>Phospholipid hydroperoxide glutathione peroxidase (PHGPx, E.C. 1.11.1...
  18. Sakamoto H, Tosaki T, Nakagawa Y. Overexpression of phospholipid hydroperoxide glutathione peroxidase modulates acetyl-CoA, 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase activity. J Biol Chem. 2002;277:50431-8 pubmed
    ..factor (PAF) by -stimulated RBL-2H3 cells was significantly suppressed by overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx)...
  19. Chavatte L, Brown B, Driscoll D. Ribosomal protein L30 is a component of the UGA-selenocysteine recoding machinery in eukaryotes. Nat Struct Mol Biol. 2005;12:408-16 pubmed
    ..We propose a model in which SBP2 and L30 carry out different functions in the UGA recoding mechanism, with the SECIS acting as a molecular switch upon protein binding. ..
  20. Wirth E, Conrad M, Winterer J, Wozny C, Carlson B, Roth S, et al. Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration. FASEB J. 2010;24:844-52 pubmed publisher
    ..Bornkamm, G. W., Coppola, V., Tessarollo, L., Schomburg, L., Köhrle, J., Hatfield, D. L., Schweizer, U. Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration. ..
  21. Vnukov V, Gutsenko O, Milutina N, Ananyan A, Danilenko A, Panina S, et al. Influence of SkQ1 on Expression of Nrf2 Transcription Factor Gene, ARE-Controlled Genes of Antioxidant Enzymes and Their Activity in Rat Blood Leukocytes. Biochemistry (Mosc). 2015;80:586-91 pubmed publisher
    ..These results indicate that antioxidant properties of SkQ1 might be realized via induction of expression of the genes regulating activity of antioxidant system elements. ..
  22. Pfeifer H, Conrad M, Roethlein D, Kyriakopoulos A, Brielmeier M, Bornkamm G, et al. Identification of a specific sperm nuclei selenoenzyme necessary for protamine thiol cross-linking during sperm maturation. FASEB J. 2001;15:1236-8 pubmed
  23. Maiorino M, Roveri A, Benazzi L, Bosello V, Mauri P, Toppo S, et al. Functional interaction of phospholipid hydroperoxide glutathione peroxidase with sperm mitochondrion-associated cysteine-rich protein discloses the adjacent cysteine motif as a new substrate of the selenoperoxidase. J Biol Chem. 2005;280:38395-402 pubmed
    ..sperm mitochondrial capsule, we confirmed, by using a proteomic approach, the presence of phospholipid hydroperoxide glutathione peroxidase (PHGPx) as a major component, and we also identified the sperm mitochondrion-associated ..
  24. Imai H, Sumi D, Hanamoto A, Arai M, Sugiyama A. Molecular cloning and functional expression of a cDNA for rat phospholipid hydroperoxide glutathione peroxidase: 3'-untranslated region of the gene is necessary for functional expression. J Biochem. 1995;118:1061-7 pubmed
    A full-length cDNA clone for phospholipid hydroperoxide glutathione peroxidase (PHGPx) was isolated from a rat brain. The cDNA was 0.761 kb in length and encoded 170 amino acids, which included a TGA-encoded selenocysteine at residue 46...
  25. Nakamura T, Imai H, Tsunashima N, Nakagawa Y. Molecular cloning and functional expression of nucleolar phospholipid hydroperoxide glutathione peroxidase in mammalian cells. Biochem Biophys Res Commun. 2003;311:139-48 pubmed
    We cloned a full-length cDNA for phospholipid hydroperoxide glutathione peroxidase (PHGPx) including exon Ib from rat and mouse testis...