The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis
Open accessAbstract
Summary Sepsis is a life-threatening condition caused by pathogen infection and associated with pyroptosis. Pyroptosis occurs upon activation of proinflammatory caspases and their subsequent cleavage of gasdermin D (GSDMD), resulting in GSDMD N-terminal fragments that form membrane pores to induce cell lysis. Here, we show that antioxidant defense enzyme glutathione peroxidase 4 (GPX4) and its ability to decrease lipid peroxidation, negatively regulate macrophage pyroptosis, and septic lethality in mice. Conditional Gpx4 knockout in myeloid lineage cells increases lipid peroxidation-dependent caspase-11 activation and GSDMD cleavage. The resultant N-terminal GSDMD fragments then trigger macrophage pyroptotic cell death in a phospholipase C gamma 1 (PLCG1)-dependent fashion. Administration of the antioxidant vitamin E that reduces lipid peroxidation, chemical inhibition of PLCG1, or genetic Caspase-11 or Gsdmd inactivation prevents polymicrobial sepsis in Gpx4−/− mice. Collectively, this study suggests that lipid peroxidation drives GSDMD-mediated pyroptosis and hence constitutes a potential therapeutic target for lethal infection.
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Cites
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Cited by
Ferroptosis: machinery and regulation
Chen, X., Li, J., Kang, R., Klionsky, D. J., & Tang, D. (2021) · Autophagy · doi:10.1080/15548627.2020.1810918 · Cited by 2,099
Self-citationLipid peroxidation and ferroptosis: The role of GSH and GPx4
Ursini, F., & Maiorino, M. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.02.027 · Cited by 1,954
NLRP3 inflammasome activation and cell death
Huang, Y., Xu, W., & Zhou, R. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00740-6 · Cited by 1,527
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
Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion
Friedmann Angeli, J. P., Krysko, D. V., & Conrad, M. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0149-1 · Cited by 1,259
Metadata
- Authors
- Kang, R., Zeng, L., Zhu, S., Xie, Y., Liu, J., Wen, Q., Cao, L., Xie, M., Ran, Q., Kroemer, G., Wang, H., Billiar, T. R., Jiang, J., & Tang, D.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 24
- Issue
- 1
- Pages
- 97-108.e4
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W2808965517
- Cited by
- 608
- References
- 18
- FWCI
- 12.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kang, R., Zeng, L., Zhu, S., Xie, Y., Liu, J., Wen, Q., Cao, L., Xie, M., Ran, Q., Kroemer, G., Wang, H., Billiar, T. R., Jiang, J., & Tang, D. (2018). Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2018.05.009
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.