The DOI matches its Crossref record; 25 of the 26 references it cites were found in a registry or an index.
The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults
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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In the citing paper
“Gpx4−/− mice display embryonic lethality with complete penetrance [547, 550, 587, 588].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [588]
In the citing paper
“Knockout of Gpx4 in mice caused embryonic lethality between E7.5 and E8.5, indicating an essential role of Gpx4 in mouse development [42, 43].”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [43]
In the citing paper
“In addition, unlike the other GPx-family members, GPx-4 knockout is lethal in mice (465).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [465]
In the citing paper
“Complete absence of GPx-4 is known to be lethal (465),”
From Redox regulation of mitochondrial function (2012) · cites this paper as [465]
Citations
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Ferroptosis: mechanisms, biology and role in disease
Jiang, X., Stockwell, B. R., & Conrad, M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00324-8 · Cited by 7,973
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732
Ferroptosis: Death by Lipid Peroxidation
Yang, W. S., & Stockwell, B. R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.014 · Cited by 3,088
Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy
Koppula, P., Zhuang, L., & Gan, B. (2020) · Protein & Cell · doi:10.1007/s13238-020-00789-5 · Cited by 2,640
Metadata
- 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
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 34
- Issue
- 4
- Pages
- 496-502
- ISSN
- 0891-5849 (ISSN-L)
- 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
- 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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