The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Transgenic Mice Overexpressing Glutathione Peroxidase 4 Are Protected against Oxidative Stress-induced Apoptosis
Open accessAbstract
Glutathione peroxidase 4 (Gpx4) is uniquely involved in the detoxification of oxidative damage to membrane lipids. Our previous studies showed that Gpx4 is essential for mouse survival and that Gpx4 deficiency makes cells vulnerable to oxidative injury. In the present study, we generated two lines of transgenic mice overexpressing Gpx4 (Tg(GPX4) mice) using a genomic clone containing the human GPX4 gene. Both lines of Tg-(GPX4) mice, Tg5 and Tg6, had elevated levels of Gpx4 (mRNA and protein) in all tissues investigated, and overexpression of Gpx4 did not cause alterations in activities of glutathione peroxidase 1, catalase, Cu/Zn superoxide dismutase, and manganese superoxide dismutase. The human GPX4 transgene rescued the lethal phenotype of null mutation of the mouse Gpx4 gene, indicating that the transgene can replace the essential role of mouse Gpx4 in mouse development. Cell death induced by t-butylhydroperoxide and diquat was significantly less in murine embryonic fibroblasts from Tg(GPX4) mice compared with wild type mice. Liver damage and lipid peroxidation induced by diquat were reduced significantly in Tg(GPX4) mice. In addition, diquat-induced apoptosis was decreased in Tg(GPX4) mice, as evidenced by attenuated caspase-3 activation and reduced cytochrome c release from mitochondria. These data demonstrate that Gpx4 plays a role in vivo in the mechanism of apoptosis induced by oxidative stress that most likely occurs through oxidative damage to mitochondrial phospholipids such as cardiolipin.
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Cites
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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: 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
Redox regulation of cell survival
Trachootham, D., Lu, W., Ogasawara, M. A., Valle, N. R.-D., & Huang, P. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1957 · Cited by 1,781
The development of the concept of ferroptosis
Hirschhorn, T., & Stockwell, B. R. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.043 · Cited by 1,052
Apoptosis and glutathione: beyond an antioxidant
Franco, R., & Cidlowski, J. A. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2009.107 · Cited by 744
Metadata
- Authors
- Ran, Q., Liang, H., Gu, M., Qi, W., Walter, C. A., Roberts, L. J., Herman, B., Richardson, A., & Van Remmen, H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-12
- Volume
- 279
- Issue
- 53
- Pages
- 55137-55146
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2138138539
- Cited by
- 256
- References
- 41
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Ran, Q., Liang, H., Gu, M., Qi, W., Walter, C. A., Roberts, L. J., Herman, B., Richardson, A., & Van Remmen, H. (2004). Transgenic Mice Overexpressing Glutathione Peroxidase 4 Are Protected against Oxidative Stress-induced Apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m410387200
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