Cited by 800Selenium in Biological SystemsRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

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The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults

Yant, Levi J, Ran, Qitao, Rao, Lin, Van Remmen, Holly, Shibatani, Toru, Belter, Jason G, Motta, Lucia, Richardson, Arlan, Prolla, Tomas A·2003·Free Radical Biology and Medicine

DOI 10.1016/s0891-5849(02)01360-6

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Abstract

Lipid peroxidation has been implicated in a variety of pathophysiological processes, including inflammation, atherogenesis, neurodegeneration, and the ageing process. Phospholipid hydroperoxide glutathione peroxidase (GPX4) is the only major antioxidant enzyme known to directly reduce phospholipid hydroperoxides within membranes and lipoproteins, acting in conjunction with alpha tocopherol (vitamin E) to inhibit lipid peroxidation. Here we describe the generation and characterization of GPX4-deficient mice by targeted disruption of the murine Gpx4 locus through homologous recombination in embryonic stem cells. Gpx4(-/-) embryos die in utero by midgestation (E7.5) and are associated with a lack of normal structural compartmentalization. Gpx4(+/-) mice display reduced levels of Gpx4 mRNA and protein in various tissues. 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. Gpx4(+/-) mice also display reduced survival in response to gamma-irradiation. Our observations establish GPX4 as an essential antioxidant enzyme in mice and suggest that it performs broad functions as a component of the mammalian antioxidant network.

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Free radicals in biology and medicine
Gutteridge, J. M. C. (1991) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(91)90478-o · Cited by 17,178
Chelex 100 as a Medium for Simple Extraction of DNA for PCR-Based Typing from Forensic Material
Walsh, P. S., Metzger, D. A., & Higuchi, R. (2013) · BioTechniques · doi:10.2144/000114018 · Cited by 5,850
Free Radicals in Biology and Medicine
Land, E. J. (1990) · International Journal of Radiation Biology · doi:10.1080/09553009014552071 · Cited by 4,871
Toxicity determined in vitro by morphological alterations and neutral red absorption
Borenfreund, E., & Puerner, J. A. (1985) · Toxicology Letters · doi:10.1016/0378-4274(85)90046-3 · Cited by 1,913
Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase
Li, Y., Huang, T.-T., Carlson, E. J., Melov, S., Ursell, P. C., Olson, J. L., Noble, L. J., Yoshimura, M. P., Berger, C., Chan, P. H., et al. (1995) · Nature Genetics · doi:10.1038/ng1295-376 · Cited by 1,789
CLONAL GROWTH OF MAMMALIAN CELLS IN VITRO
Puck, T. T., Marcus, P. I., & Cieciura, S. J. (1956) · The Journal of Experimental Medicine · doi:10.1084/jem.103.2.273 · Cited by 1,143
Tissue-specific functions of individual glutathione peroxidases
Brigelius-Flohé, R. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00173-2 · Cited by 1,114
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Ursini, F., Heim, S., Kieß, M., Maiorino, M., Roveri, A., Wissing, J. B., & Flohé, L. (1999) · Science · doi:10.1126/science.285.5432.1393 · Cited by 902
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Ho, Y., Magnenat, J.-L., Bronson, R. T., Cao, J., Gargano, M. D., Sugawara, M., & Funk, C. D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16644 · Cited by 562
The role of selenium peroxidases in the protection against oxidative damage of membranes
Ursini, F., & Bindoli, A. (1987) · Chemistry and Physics of Lipids · doi:10.1016/0009-3084(87)90053-3 · Cited by 391

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Authors: Yant, L. J., Ran, Q., Rao, L., Van Remmen, H., Shibatani, T., Belter, J. G., Motta, L., Richardson, A., & Prolla, T. A.
Affiliations: University of Wisconsin–Madison (US)
The University of Texas at San Antonio Health Science Center (US)
Corresponding author: Prolla, Tomas A
ORCID: Yant, Levi J
Ran, Qitao
Rao, Lin
Richardson, Arlan
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2003-02
Volume: 34
Issue: 4
Pages: 496-502
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/s0891-5849(02)01360-6
OpenAlex: W2165072468
Cited by: 797
References: 26
Citations by year: 2026: 29 · 2025: 41 · 2024: 82 · 2023: 59 · 2022: 52 · 2021: 51 · 2020: 43 · 2019: 32 · 2018: 39 · 2017: 35 · 2016: 22 · 2015: 27 · 2014: 27 · 2013: 24 · 2012: 26
FWCI: 16.61
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Free Radical Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs
National Institutes of Health
University of Texas Health Science Center at San Antonio
National Institute on Aging (P03-AG13319, 1 P01 AG19316, P01AG019316)
National Cancer Institute
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords: GPX4, phospholipid hydroperoxide glutathione peroxidase, selenoproteins, lipid peroxidation, antioxidant enzymes, embryonic lethality, oxidative stress, gamma-irradiation sensitivity, paraquat, tert-butyl hydroperoxide, hydrogen peroxide, vitamin E, mouse development
MeSH terms: Phospholipid Hydroperoxide Glutathione Peroxidase, Animals, Cell Line, Embryo, Mammalian, Female, Fetal Death, Embryonic and Fetal Development, Fibroblasts, Gamma Rays, Gestational Age, Glutathione Peroxidase, Hydrogen Peroxide, Mice, Inbred C57BL, Paraquat, Pregnancy, RNA, Messenger, Blotting, Northern, Blotting, Western, Mice, Knockout, Oxidative Stress, tert-Butylhydroperoxide, In Situ Nick-End Labeling, Mice

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The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults

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