The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal loss in brain
Open accessAbstract
Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme important in reducing hydroperoxides in membrane lipids and lipoproteins. Gpx4 is essential for survival of embryos and neonatal mice; however, whether Gpx4 is required for adult animals remains unclear. In this study, we generated a floxed Gpx4 mouse (Gpx4(f/f)), in which exons 2–4 of Gpx4 gene are flanked by loxP sites. We then cross-bred the Gpx4(f/f) mice with a tamoxifen (tam)-inducible Cre transgenic mouse (R26CreER mice) to obtain mice in which the Gpx4 gene could be ablated by tam administration (Gpx4(f/f)/Cre mice). After treatment with tam, adult Gpx4(f/f)/Cre mice (6–9 months of age) showed a significant reduction of Gpx4 levels (a 75–85 % decrease) in tissues such as brain, liver, lung and kidney. Tam-treated Gpx4(f/f)/Cre mice lost body weight and died within 2 weeks, indicating that Gpx4 is essential for survival of adult animals. Tam-treated Gpx4(f/f)/Cre mice exhibited increased mitochondrial damage, as evidenced by the elevated 4-hydroxylnonenal (4-HNE) level, decreased activities of electron transport chain complex I and IV, and reduced ATP production in liver. Tam treatment also significantly elevated apoptosis in Gpx4(f/f)/Cre mice. Moreover, tam-treated Gpx4(f/f)/Cre mice showed neuronal loss in hippocampus region and had increased astrogliosis. These data indicate that Gpx4 is essential for mitochondria integrity and survival of neurons in adult animals.
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Cites
Oxidative Stress, Glutamate, and Neurodegenerative Disorders
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Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors
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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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Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis
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Cited by
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695
Self-citationBrigelius-Flohé, R., & Maiorino, M. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.11.020 · Cited by 1,904
Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition
Hangauer, M. J., Viswanathan, V. S., Ryan, M. J., Bole, D., Eaton, J. K., Matov, A., Galeas, J., Dhruv, H. D., Berens, M. E., Schreiber, S. L., et al. (2017) · Nature · doi:10.1038/nature24297 · Cited by 1,799
Ferroptosis: Mechanisms and links with diseases
Yan, H.-F., Zou, T., Tuo, Q.-Z., Xu, S., Li, H., Belaidi, A. A., & Lei, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00428-9 · Cited by 1,471
Metadata
- Authors
- Yoo, S.-E., Chen, L., Na, R., Liu, Y., Rios, C., Van Remmen, H., Richardson, A., & Ran, Q.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 52
- Issue
- 9
- Pages
- 1820-1827
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2074191005
- Cited by
- 248
- References
- 8
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- green
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- Yoo, S.-E., Chen, L., Na, R., Liu, Y., Rios, C., Van Remmen, H., Richardson, A., & Ran, Q. (2012). Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal loss in brain. Free Radical Biology and Medicine. https://doi.org/10.1016/j.freeradbiomed.2012.02.043
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