Skip to main content
SpringerLink
Log in
Book cover

Studies on Experimental Models pp 265–278Cite as

The Use of Gpx4 Knockout Mice and Transgenic Mice to Study the Roles of Lipid Peroxidation in Diseases and Aging

  • Chapter
  • First Online:

  • 1509 Accesses

Abstract

Lipid peroxidation, a primary event of oxidative stress, is considered to be important in disease pathogenesis and aging. Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme that can directly reduce lipid hyproperoxides in membrane lipids. Several Gpx4 knockout mouse models and Gpx4 transgenic mouse models have been generated over the past 7 years, and data collected from those models indicate that Gpx4 plays an essential role in protecting against lipid peroxidation. Because Gpx4 knockout mice and Gpx4 transgenic mice show increased lipid peroxidation and decreased lipid peroxidation, respectively, those models were used to investigate the roles of lipid peroxidation in aging and disease. For example, lifespan studies showed that Gpx4 heterozygous knockout mice and Gpx4 transgenic mice altered lifespans, indicating that mild change in lipid peroxidation does not affect aging. However, studies using Gpx4 transgenic and knockout models showed that overexpression of Gpx4 protected against Aβ toxicity and that deficiency of Gpx4 resulted in increased amyloidogenesis in brain, indicating that lipid peroxidation is important in the pathogenesis of Alzheimer’s disease. Studies using Gpx4 transgenic mice also showed that overexpression of Gpx4 reduced atherosclerosis and attenuated cardiac ischemia/reperfusion injury, suggesting that lipid peroxidation is important in cardiovascular disease. Therefore, Gpx4 knockout and transgenic mouse models are useful in ­dissecting the in vivo roles of lipid peroxidation in diseases and aging.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Porter, N.A., Caldwell, S.E., and Mills, K.A. (1995). Mechanisms of free radical oxidation of unsaturated lipids. Lipid 30, 277–290.

    Article  CAS  Google Scholar 

  2. Halliwell, B. (1999). Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic. Res. 31, 261–272.

    Article  PubMed  CAS  Google Scholar 

  3. Richter, C. (1987). Biophysical consequences of lipid peroxidation in membranes. Chem. Phys. Lipids 44, 175–189.

    Article  PubMed  CAS  Google Scholar 

  4. Girotti, A.W. (1998). Lipid hydroperoxide generation, turnover, and effector action in biological systems. J. Lipid Res. 39, 1529–1542.

    PubMed  CAS  Google Scholar 

  5. Allen, R.G., Farmer, K.J., Newton, R.K., and Sohal, R.S. (1984). Effects of paraquat administration on longevity, oxygen consumption, lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, inorganic peroxides and glutathione in the adult housefly. Comp Biochem. Physiol C. 78, 283–288.

    Article  PubMed  CAS  Google Scholar 

  6. Kergonou, J.F., Thiriot, C., Braquet, M., Ducousso, R., and Rocquet, G. (1986). Influence of whole-body gamma-irradiation upon rat erythrocyte: lipid peroxidation and osmotic fragility. Biochimie 68, 311–318.

    Article  PubMed  CAS  Google Scholar 

  7. Mattson, M.P. (2004). Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Ann. N. Y. Acad. Sci. 1012, 37–50.

    Article  PubMed  CAS  Google Scholar 

  8. Meerson, F.Z., Kagan, V.E., Kozov, Y.P., Belkina, L.M., and Arkhipenko, Y.V. (1982). The role of llipid peroxidation in pathogenesis of ischemia damage and the antioxidant protection of the heart. Basic Research in Cardiology 77, 163–185.

    Google Scholar 

  9. Butterfield, D.A., Reed, T., Perluigi, M., De Marco, C., Coccia, R., Cini, C., and Sultana, R. (2006). Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2-nonenal, in brain from persons with mild cognitive impairment. Neurosci. Lett. 397, 170–173.

    Article  PubMed  CAS  Google Scholar 

  10. Gago-Dominguez, M., Jiang, X., and Castelao, J.E. (2007). Lipid peroxidation, oxidative stress genes and dietary factors in breast cancer protection: a hypothesis. Breast Cancer Res. 9, 201.

    Article  PubMed  Google Scholar 

  11. Marnett, L.J. (2000). Oxyradicals and DNA damage. Carcinogenesis 21, 361–370.

    Article  PubMed  CAS  Google Scholar 

  12. Subbanagounder, G., Leitinger, N., Shih, P.T., Faull, K.F., and Berliner, J.A. (1999). Evidence that phospholipid oxidation products and/or platelet- activating factor play an important role in early atherogenesis : in vitro and In vivo inhibition by WEB 2086. Circ. Res. 85, 311–318.

    Article  PubMed  CAS  Google Scholar 

  13. Rikans, L.E. and Hornbrook, K.R. (1997). Lipid peroxidation, antioxidant protection and aging. Biochim. Biophys. Acta 1362, 116–127.

    Article  PubMed  CAS  Google Scholar 

  14. Sanz, A., Pamplona, R., and Barja, G. (2006). Is the mitochondrial free radical theory of aging intact? Antioxid. Redox. Signal. 8, 582–599.

    Article  PubMed  CAS  Google Scholar 

  15. Yu, B.P. (1993). Antioxidant action of dietary restriction in aging. J. Nutr. Sci. Vitaminol. 39, 575–583.

    Article  Google Scholar 

  16. Thomas, J.P., Maiorino, M., Ursini, F., and Girotti, A.W. (1990). Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. J. Biol. Chem. 265, 454–461.

    PubMed  CAS  Google Scholar 

  17. Ursini, F., Maiorino, M., and Gregolin, C. (1985). The selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Biochim. Biophys. Acta 839, 62–70.

    Article  PubMed  CAS  Google Scholar 

  18. Brigelius-Flohe, R. (1999). Tissue-specific functions of individual glutathione peroxidases. Free Radic. Biol. Med. 27, 951–965.

    Article  PubMed  CAS  Google Scholar 

  19. Beyer, W., Imlay, J., and Fridovich, I. (1991). Superoxide dismutases. Prog. Nucleic Acid Res. Mol. Biol. 40, 221–253.

    Article  PubMed  CAS  Google Scholar 

  20. Knopp, E.A., Arndt, T.L., Eng, K.L., Caldwell, M., LeBoeuf, R.C., Deeb, S.S., and O’Brien, K.D. (1999). Murine phospholipid hydroperoxide glutathione peroxidase: cDNA sequence, tissue expression, and mapping. Mamm. Genome 10, 601–605.

    Article  PubMed  CAS  Google Scholar 

  21. Nam, S., Nakamuta, N., Kurohmaru, M., and Hayashi, Y. (1997). Cloning and sequencing of the mouse cDNA encoding a phospholipid hydroperoxide glutathione peroxidase. Gene 198, 245–249.

    Article  PubMed  CAS  Google Scholar 

  22. Brigelius-Flohe, R., Friedrichs, B., Maurer, S., Schultz, M., and Streicher, R. (1997). Interleukin-1-induced nuclear factor kappa B activation is inhibited by overexpression of phospholipid hydroperoxide glutathione peroxidase in a human endothelial cell line. Biochem J. 328 ( Pt 1), 199–203.

    PubMed  CAS  Google Scholar 

  23. Scheerer, P., Borchert, A., Krauss, N., Wessner, H., Gerth, C., Hohne, W., and Kuhn, H. (2007). Structural basis for catalytic activity and enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4 (GPx4). Biochemistry 46, 9041–9049.

    Article  PubMed  CAS  Google Scholar 

  24. Antunes, F., Salvador, A., and Pinto, R.E. (1995). PHGPx and phospholipase A2/GPx: comparative importance on the reduction of hydroperoxides in rat liver mitochondria. Free Radic. Biol. Med. 19, 669–677.

    Article  PubMed  CAS  Google Scholar 

  25. Imai, H. and Nakagawa, Y. (2003). Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells. Free Radic. Biol. Med. 34, 145–169.

    Article  PubMed  CAS  Google Scholar 

  26. Nomura, K., Imai, H., Koumura, T., Kobayashi, T., and Nakagawa, Y. (2000). Mitochondrial phospholipid hydroperoxide glutathione peroxidase inhibits the release of cytochrome c from mitochondria by suppressing the peroxidation of cardiolipin in hypoglycaemia-induced apoptosis. Biochem J. 351, 183–193.

    Article  PubMed  CAS  Google Scholar 

  27. Petrosillo, G., Ruggiero, F.M., and Paradies, G. (2003). Role of reactive oxygen species and cardiolipin in the release of cytochrome c from mitochondria. FASEB J. 17, 2202–2208.

    Article  PubMed  CAS  Google Scholar 

  28. Kagan, V.E., Tyurin, V.A., Jiang, J., Tyurina, Y.Y., Ritov, V.B., Amoscato, A.A., Osipov, A.N., Belikova, N.A., Kapralov, A.A., Kini, V., Vlasova, I.I., Zhao, Q., Zou, M., Di, P., Svistunenko, D.A., Kurnikov, I.V., and Borisenko, G.G. (2005). Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat. Chem. Biol. 1, 223–232.

    Article  PubMed  CAS  Google Scholar 

  29. Liang, H., Ran, Q., Jang, Y.C., Holstein, D., Lechleiter, J., McDonald-Marsh, T., Musatov, A., Song, W., Van Remmen, H., and Richardson, A. (2009). Glutathione peroxidase 4 differentially regulates the release of apoptogenic proteins from mitochondria. Free Radic. Biol. Med. 47, 312–320.

    Article  PubMed  CAS  Google Scholar 

  30. Kriska, T., Korytowski, W., and Girotti, A.W. (2002). Hyperresistance to photosensitized lipid peroxidation and apoptotic killing in 5-aminolevulinate-treated tumor cells overexpressing mitochondrial GPX4. Free Radic. Biol. Med. 33, 1389–1402.

    Article  PubMed  CAS  Google Scholar 

  31. Nomura, K., Imai, H., Koumura, T., Arai, M., and Nakagawa, Y. (1999). Mitochondrial phospholipid hydroperoxide glutathione peroxidase suppresses apoptosis mediated by a mitochondrial death pathway. J. Biol. Chem. 274, 29294–29302.

    Article  PubMed  CAS  Google Scholar 

  32. Ran, Q., Liang, H., Gu, M., Qi, W., Walter, C.A., Roberts, L.J., Herman, B., Richardson, A., and Van Remmen, H. (2004). Transgenic mice overexpressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis. J. Biol. Chem. 279, 55137–55146.

    Article  PubMed  CAS  Google Scholar 

  33. Chang, W.C. (2003). Identification of an endogenous inhibitor of arachidonate metabolism in human epidermoid carcinoma A431 cells. J. Biomed. Sci. 10, 599–606.

    Article  PubMed  CAS  Google Scholar 

  34. Sakamoto, H., Imai, H., and Nakagawa, Y. (2000). Involvement of phospholipid hydroperoxide glutathione peroxidase in the modulation of prostaglandin D2 synthesis. J. Biol. Chem. 275, 40028–40035.

    Article  PubMed  CAS  Google Scholar 

  35. Imai, H., Narashima, K., Arai, M., Sakamoto, H., Chiba, N., and Nakagawa, Y. (1998). Suppression of leukotriene formation in RBL-2H3 cells that overexpressed phospholipid hydroperoxide glutathione peroxidase. J. Biol. Chem. 273, 1990–1997.

    Article  PubMed  CAS  Google Scholar 

  36. Huang, H.S., Chen, C.J., Suzuki, H., Yamamoto, S., and Chang, W.C. (1999a). Inhibitory effect of phospholipid hydroperoxide glutathione peroxidase on the activity of lipoxygenases and cyclooxygenases. Prostaglandins Other Lipid Mediat. 58, 65–75.

    Article  PubMed  CAS  Google Scholar 

  37. Weitzel, F. and Wendel, A. (1993). Selenoenzymes regulate the activity of leukocyte 5-lipoxygenase via the peroxide tone. J. Biol. Chem. 268, 6288–6292.

    PubMed  CAS  Google Scholar 

  38. Seiler, A., Schneider, M., Forster, H., Roth, S., Wirth, E.K., Culmsee, C., Plesnila, N., Kremmer, E., Radmark, O., Wurst, W., Bornkamm, G.W., Schweizer, U., and Conrad, M. (2008). Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 8, 237–248.

    Article  PubMed  CAS  Google Scholar 

  39. Maiorino, M., Wissing, J.B., Brigelius-Flohe, R., Calabrese, F., Roveri, A., Steinert, P., Ursini, F., and Flohe, L. (1998). Testosterone mediates expression of the selenoprotein PHGPx by induction of spermatogenesis and not by direct transcriptional gene activation. FASEB J. 12, 1359–1370.

    PubMed  CAS  Google Scholar 

  40. Ursini, F., Heim, S., Kiess, M., Maiorino, M., Roveri, A., Wissing, J., and Flohe, L. (1999). Dual function of the selenoprotein PHGPx during sperm maturation [see comments]. Science 285, 1393–1396.

    Article  PubMed  CAS  Google Scholar 

  41. Conrad, M., Moreno, S.G., Sinowatz, F., Ursini,F., Kolle, S., Roveri, A., Brielmeier, M., Wurst, W., Maiorino, M., and Bornkamm, G.W. (2005). The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a protein thiol peroxidase contributing to sperm chromatin stability. Mol. Cell Biol. 25, 7637–7644.

    Article  PubMed  CAS  Google Scholar 

  42. Arai, M., Imai, H., Sumi, D., Imanaka, T., Takano, T., Chiba, N., and Nakagawa, Y. (1996). Import into mitochondria of phospholipid hydroperoxide glutathione peroxidase requires a leader sequence. Biochem Biophys. Res Commun. 227, 433–439.

    Article  PubMed  CAS  Google Scholar 

  43. Liang, H., Yoo, S.E., Na, R., Walter, C.A., Richardson, A., and Ran, Q. (2009). Short form glutathione peroxidase 4 is the essential isoform required for survival and somatic mitochondrial functions. J. Biol. Chem. 284, 30836–30844.

    Google Scholar 

  44. Schneider, M., Forster, H., Boersma, A., Seiler, A., Wehnes, H., Sinowatz, F., Neumuller, C., Deutsch, M.J., Walch, A., Hrabe,d.A., Wurst, W., Ursini, F., Roveri, A., Maleszewski, M., Maiorino, M., and Conrad, M. (2009). Mitochondrial glutathione peroxidase 4 disruption causes male infertility. FASEB J. 23, 3233–3242.

    Google Scholar 

  45. Imai, H., Hirao, F., Sakamoto, T., Sekine, K., Mizukura, Y., Saito, M., Kitamoto, T., Hayasaka, M., Hanaoka, K., and Nakagawa, Y. (2003). Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene. Biochem. Biophys. Res. Commun. 305, 278–286.

    Article  PubMed  CAS  Google Scholar 

  46. Yant, L.J., Ran, Q., Rao, L., Van Remmen, H., Shibatani, T., Belter, J.G., Motta, L., Richardson, A., and Prolla, T.A. (2003). The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic. Biol. Med. 34, 496–502.

    Article  PubMed  CAS  Google Scholar 

  47. Ran, Q., Van Remmen, H., Gu, M., Qi, W., Roberts, L.J., Prolla, T., and Richardson, A. (2003). Embryonic fibroblasts from Gpx4+/- mice: a novel model for studying the role of membrane peroxidation in biological processes. Free Radic. Biol. Med. 35, 1101–1109.

    Article  PubMed  CAS  Google Scholar 

  48. Chen, L., Na, R., Gu, M., Richardson, A., and Ran, Q. (2008). Lipid peroxidation up-regulates BACE1 expression in vivo: a possible early event of amyloidogenesis in Alzheimer’s disease. J. Neurochem. 107, 197–207.

    Article  PubMed  CAS  Google Scholar 

  49. Ran, Q., Liang, H., Ikeno, Y., Qi, W., Prolla,T.A., Roberts,L.J., Wolf,N., VanRemmen,H., and Richardson,A. (2007). Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis. J. Gerontol. A Biol. Sci. Med. Sci. 62, 932–942.

    Article  PubMed  Google Scholar 

  50. Ran, Q., Gu, M., Van Remmen, H., Strong, R., Roberts, J.L., and Richardson, A. (2006). Glutathione peroxidase 4 protects cortical neurons from oxidative injury and amyloid toxicity. J. Neurosci. Res. 84, 202–208.

    Article  PubMed  CAS  Google Scholar 

  51. Liang, H., Van Remmen, H., Frohlich, V., Lechleiter, J., Richardson, A., and Ran, Q. (2007). Gpx4 protects mitochondrial ATP generation against oxidative damage. Biochem. Biophys. Res. Commun. 356, 893–898.

    Article  PubMed  CAS  Google Scholar 

  52. Lu, L., Oveson, B.C., Jo, Y.J., Lauer, T., Usui, S., Komeima, K., Xie, B., and Campochiaro, P.A. (2008). Increased Expression of Glutathione Peroxidase 4 Strongly Protects Retina from Oxidative Damage. Antioxid. Redox. Signal.

    Google Scholar 

  53. Dabkowski, E.R., Williamson, C.L., and Hollander, J.M. (2008b). Mitochondria-specific transgenic overexpression of phospholipid hydroperoxide glutathione peroxidase (GPx4) attenuates ischemia/reperfusion-associated cardiac dysfunction. Free Radic. Biol Med. 45, 855–865.

    Article  PubMed  CAS  Google Scholar 

  54. Ames, B.N., Shigenaga, M.K., and Hagen, T.M. (1995). Mitochondrial decay in aging. Biochim. Biophys. Acta Mol. Basis Dis. 1271, 165–170.

    Article  Google Scholar 

  55. Harman, D. (1956). Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11, 298–300.

    Article  PubMed  CAS  Google Scholar 

  56. Bohr, V.A. and Anson, R.M. (1995). DNA damage, mutation and fine structure DNA repair in aging. Mutation Res. 338, 25–34.

    Article  PubMed  CAS  Google Scholar 

  57. Warner, H.R. (1994). Superoxide dismutase, aging, and degenerative disease. Free Radic. Biol. Med. 17, 249–258.

    Article  PubMed  CAS  Google Scholar 

  58. Laganiere, S. and Yu, B.P. (1993). Modulation of membrane phospholipid fatty acid composition by age and food restriction. Gerontology 39, 7–18.

    Article  PubMed  CAS  Google Scholar 

  59. Lambert, A.J., Portero-Otin, M., Pamplona, R., and Merry, B.J. (2004). Effect of ageing and caloric restriction on specific markers of protein oxidative damage and membrane peroxidizability in rat liver mitochondria. Mech. Ageing Dev. 125, 529–538.

    Article  PubMed  CAS  Google Scholar 

  60. Pamplona, R., Portero-Otin, M., Requena, J., Gredilla, R., and Barja, G. (2002). Oxidative, ­glycoxidative and lipoxidative damage to rat heart mitochondrial proteins is lower after 4 months of caloric restriction than in age-matched controls. Mech. Ageing Dev. 123, 1437–1446.

    Article  PubMed  CAS  Google Scholar 

  61. Franceschi, C. (1989). Cell proliferation, cell death and aging. [Review]. Aging 1, 3–15.

    PubMed  CAS  Google Scholar 

  62. Van Remmen, H., Ikeno, Y., Hamilton, M., Pahlavani, M., Wolf, N., Thorpe, S.R., Alderson, N.L., Baynes, J.W., Epstein, C.J., Huang, T.T., Nelson, J., Strong,R., and Richardson, A. (2003). Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16, 29–37.

    Article  PubMed  Google Scholar 

  63. Perez, V.I., Bokov, A., Remmen, H.V., Mele, J., Ran, Q., Ikeno, Y., and Richardson, A. (2009). Is the oxidative stress theory of aging dead? Biochim. Biophys. Acta.

    Google Scholar 

  64. Schriner, S.E., Linford, N.J., Martin, G.M., Treuting, P., Ogburn, C.E., Emond, M., Coskun, P.E., Ladiges, W., Wolf, N., Van Remmen, H., Wallace, D.C., and Rabinovitch, P.S. (2005). Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308, 1909–1911.

    Article  PubMed  CAS  Google Scholar 

  65. Park, J. and Floyd, R.A. (1992). Lipid peroxidation products mediate the formation of 8-hydroxydeoxyguanosine in DNA. Free Radic. Biol. Med. 12, 245–250.

    Google Scholar 

  66. Butterfield, D.A. and Lauderback, C.M. (2002). Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic. Biol. Med. 32, 1050–1060.

    Article  PubMed  CAS  Google Scholar 

  67. Pratico, D., Clark, C.M., Liun, F., Rokach, J., Lee, V.Y., and Trojanowski, J.Q. (2002). Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch. Neurol. 59, 972–976.

    Google Scholar 

  68. Williams, T.I., Lynn, B.C., Markesbery, W.R., and Lovell, M.A. (2006). Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer’s disease. Neurobiol. Aging 27, 1094–1099.

    Article  PubMed  CAS  Google Scholar 

  69. Hardy, J. and Selkoe, D.J. (2002). The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297, 353–356.

    Google Scholar 

  70. Behl, C., Davis, J.B., Lesley, R., and Schubert, D. (1994). Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77, 817–827.

    Article  PubMed  CAS  Google Scholar 

  71. Hensley, K., Carney, J.M., Mattson, M.P., Aksenova, M., Harris, M., Wu, J.F., Floyd, R.A., and Butterfield, D.A. (1994). A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A 91, 3270–3274.

    Article  PubMed  CAS  Google Scholar 

  72. Huang, X., Atwood, C.S., Hartshorn, M.A., Multhaup, G., Goldstein, L.E., Scarpa, R.C., Cuajungco, M.P., Gray, D.N., Lim, J., Moir, R.D., Tanzi, R.E., and Bush, A.I. (1999b). The A beta peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 38, 7609–7616.

    Article  PubMed  CAS  Google Scholar 

  73. Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., and Cole, G. (1996). Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274, 99–102.

    Article  PubMed  CAS  Google Scholar 

  74. Velliquette, R.A., O’Connor, T., and Vassar, R. (2005). Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer’s disease pathogenesis. J. Neurosci. 25, 10874–10883.

    Google Scholar 

  75. Tamagno, E., Bardini, P., Obbili, A., Vitali, A., Borghi, R., Zaccheo, D., Pronzato, M.A., Danni, O., Smith, M.A., Perry, G., and Tabaton, M. (2002). Oxidative stress increases expression and activity of BACE in NT2 neurons. Neurobiol. Dis. 10, 279–288.

    Google Scholar 

  76. Tamagno, E., Parola, M., Bardini, P., Piccini, A., Borghi, R., Guglielmotto, M., Santoro, G., Davit, A., Danni, O., Smith, M.A., Perry, G., and Tabaton, M. (2005). Beta-site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stress-activated protein kinases pathways. J. Neurochem. 92, 628–636.

    Google Scholar 

  77. Davi, G., Ciabattoni, G., Consoli, A., Mezzetti, A., Falco, A., Santarone, S., Pennese, E., Vitacolonna, E., Bucciarelli, T., Costantini, F., Capani, F., and Patrono, C. (1999). In vivo formation of 8-iso-prostaglandin f2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation. Circulation 99, 224–229.

    Article  PubMed  CAS  Google Scholar 

  78. Block, G., Dietrich, M., Norkus, E.P., Morrow, J.D., Hudes, M., Caan, B., and Packer, L. (2002). Factors associated with oxidative stress in human populations. Am. J. Epidemiol. 156, 274–285.

    Article  PubMed  Google Scholar 

  79. Davi, G., Guagnano, M.T., Ciabattoni, G., Basili, S., Falco, A., Marinopiccoli, M., Nutini, M., Sensi, S., and Patrono, C. (2002). Platelet activation in obese women: role of inflammation and oxidant stress. JAMA 288, 2008–2014.

    Article  PubMed  CAS  Google Scholar 

  80. Davi, G., Alessandrini, P., Mezzetti, A., Minotti, G., Bucciarelli, T., Costantini, F., Cipollone, F., Bon, G.B., Ciabattoni, G., and Patrono, C. (1997). In vivo formation of 8-Epi-prostaglandin F2 alpha is increased in hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 17, 3230–3235.

    Article  PubMed  CAS  Google Scholar 

  81. Morrow, J.D., Frei, B., Longmire, A.W., Gaziano, J.M., Lynch, S.M., Shyr, Y., Strauss, W.E., Oates, J.A., and Roberts, L.J. (1995). Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. N. Engl. J Med. 332, 1198–1203.

    Article  PubMed  CAS  Google Scholar 

  82. Castelao, J.E. and Gago-Dominguez,M. (2008). Risk factors for cardiovascular disease in women: relationship to lipid peroxidation and oxidative stress. Med. Hypotheses 71, 39–44.

    Article  PubMed  CAS  Google Scholar 

  83. Steinberg, D., Parthasarathy, S., Carew, T.E., Khoo, J.C., and Witztum, J.L. (1989). Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N. Engl. J Med. 320, 915–924.

    Article  PubMed  CAS  Google Scholar 

  84. Hulten, L.M., Lindmark, H., Diczfalusy, U., Bjorkhem, I., Ottosson, M., Liu, Y., Bondjers, G., and Wiklund, O. (1996). Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages. J. Clin. Invest 97, 461–468.

    Article  PubMed  CAS  Google Scholar 

  85. Pratico, D., Iuliano, L., Mauriello, A., Spagnoli, L., Lawson, J.A., Rokach, J., Maclouf, J., Violi, F., and FitzGerald, G.A. (1997). Localization of distinct F2-isoprostanes in human atherosclerotic lesions. J. Clin. Invest 100, 2028–2034.

    Article  PubMed  CAS  Google Scholar 

  86. Guo, Z., Ran, Q., Roberts, L.J., Zhou, L., Richardson, A., Sharan, C., Wu, D., and Yang, H. (2008). Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice. Free Radic. Biol. Med. 44, 343–352.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The studies were supported by a Merit Award (Q.R.) from the Department of Veteran Affairs.

Author information

Authors and Affiliations

  1. Department of Cellular and Structural Biology, University of Texas Health Science Centre at San Antonio, San Antonio, TX, 78229, USA

    Qitao Ran

  2. Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA

    Qitao Ran

  3. South Texas Veterans Health Care System, San Antonio, TX, 78229, USA

    Qitao Ran

Authors
  1. Qitao Ran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hanyu Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qitao Ran .

Editor information

Editors and Affiliations

  1. Dept. Health & Caring Sciences, University Uppsala, Döbelnsgatan 2, Uppsala, 752 37, Sweden

    Samar Basu

  2. Dept. Surgical Sciences, Anaesthesiology, & Intensive Care, Uppsala University Hospital, Akademiska Sjukhuset, Uppsala, 751 85, Sweden

    Lars Wiklund

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Ran, Q., Liang, H. (2011). The Use of Gpx4 Knockout Mice and Transgenic Mice to Study the Roles of Lipid Peroxidation in Diseases and Aging. In: Basu, S., Wiklund, L. (eds) Studies on Experimental Models. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-956-7_12

Download citation

Publish with us

Policies and ethics

Search

Navigation