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Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury
Radiation-induced lung injury (RILI) is one of the most common, serious, and dose-limiting toxicities of thoracic radiotherapy. A primary cause for this is the radiation-induced cell death. Ferroptosis is a recently recognized form of regulated cell death, characterized by the accumulation of lipid...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277166/ https://www.ncbi.nlm.nih.gov/pubmed/35847598 http://dx.doi.org/10.1155/2022/8973509 |
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author | Li, Xuan Chen, Jingyao Yuan, Sujuan Zhuang, Xibing Qiao, Tiankui |
author_facet | Li, Xuan Chen, Jingyao Yuan, Sujuan Zhuang, Xibing Qiao, Tiankui |
author_sort | Li, Xuan |
collection | PubMed |
description | Radiation-induced lung injury (RILI) is one of the most common, serious, and dose-limiting toxicities of thoracic radiotherapy. A primary cause for this is the radiation-induced cell death. Ferroptosis is a recently recognized form of regulated cell death, characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). The ROS generated by irradiation might be the original trigger of ferroptosis in RILI. In addition, activation of the P62-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (NRF2) pathway has been shown to blunt ferroptosis and thus acts as a protective factor. Therefore, this study aimed to explore the protective effect of the P62-Keap1-NRF2 pathway against radiation-induced ferroptosis in alveolar epithelial cells. First, we found that radiation induced ferroptosis in vitro using a RILI cell model, which could be significantly reduced by ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor. Additionally, overexpression of P62 interacted with Keap1 to facilitate the translocation of NRF2 into the nucleus and promote the expression of its target proteins, including quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), and ferritin heavy chain 1 (FTH1). In summary, our results demonstrated that the activation of the P62-Keap1-NRF2 pathway prevents radiation-induced ferroptosis in RILI cells, providing a theoretical basis of finding a potential therapeutic approach for RILI. |
format | Online Article Text |
id | pubmed-9277166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-92771662022-07-14 Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury Li, Xuan Chen, Jingyao Yuan, Sujuan Zhuang, Xibing Qiao, Tiankui Oxid Med Cell Longev Research Article Radiation-induced lung injury (RILI) is one of the most common, serious, and dose-limiting toxicities of thoracic radiotherapy. A primary cause for this is the radiation-induced cell death. Ferroptosis is a recently recognized form of regulated cell death, characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). The ROS generated by irradiation might be the original trigger of ferroptosis in RILI. In addition, activation of the P62-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (NRF2) pathway has been shown to blunt ferroptosis and thus acts as a protective factor. Therefore, this study aimed to explore the protective effect of the P62-Keap1-NRF2 pathway against radiation-induced ferroptosis in alveolar epithelial cells. First, we found that radiation induced ferroptosis in vitro using a RILI cell model, which could be significantly reduced by ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor. Additionally, overexpression of P62 interacted with Keap1 to facilitate the translocation of NRF2 into the nucleus and promote the expression of its target proteins, including quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), and ferritin heavy chain 1 (FTH1). In summary, our results demonstrated that the activation of the P62-Keap1-NRF2 pathway prevents radiation-induced ferroptosis in RILI cells, providing a theoretical basis of finding a potential therapeutic approach for RILI. Hindawi 2022-07-05 /pmc/articles/PMC9277166/ /pubmed/35847598 http://dx.doi.org/10.1155/2022/8973509 Text en Copyright © 2022 Xuan Li et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Li, Xuan Chen, Jingyao Yuan, Sujuan Zhuang, Xibing Qiao, Tiankui Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury |
title | Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury |
title_full | Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury |
title_fullStr | Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury |
title_full_unstemmed | Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury |
title_short | Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury |
title_sort | activation of the p62-keap1-nrf2 pathway protects against ferroptosis in radiation-induced lung injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277166/ https://www.ncbi.nlm.nih.gov/pubmed/35847598 http://dx.doi.org/10.1155/2022/8973509 |
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