Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis
Abstract Background Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death world...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Respiratory Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12931-020-01500-2 |
| _version_ | 1811294740428095488 |
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| author | Yu-bao Qiu Bin-bin Wan Gang Liu Ya-xian Wu Dan Chen Mu-dan Lu Jun-liang Chen Ren-qiang Yu Dao-zhen Chen Qing-feng Pang |
| author_facet | Yu-bao Qiu Bin-bin Wan Gang Liu Ya-xian Wu Dan Chen Mu-dan Lu Jun-liang Chen Ren-qiang Yu Dao-zhen Chen Qing-feng Pang |
| author_sort | Yu-bao Qiu |
| collection | DOAJ |
| description | Abstract Background Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis. Methods we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms. Results Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning. Conclusions These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI. |
| first_indexed | 2024-04-13T05:21:55Z |
| format | Article |
| id | doaj.art-5780605b65434064895990b6016c1db4 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-13T05:21:55Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-5780605b65434064895990b6016c1db42022-12-22T03:00:43ZengBMCRespiratory Research1465-993X2020-09-0121111610.1186/s12931-020-01500-2Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosisYu-bao Qiu0Bin-bin Wan1Gang Liu2Ya-xian Wu3Dan Chen4Mu-dan Lu5Jun-liang Chen6Ren-qiang Yu7Dao-zhen Chen8Qing-feng Pang9Wuxi School of Medicine, Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityCentral Laboratory, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical UniversityWuxi School of Medicine, Jiangnan UniversityCentral Laboratory, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical UniversityCentral Laboratory, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical UniversityWuxi School of Medicine, Jiangnan UniversityAbstract Background Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis. Methods we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms. Results Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning. Conclusions These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.http://link.springer.com/article/10.1186/s12931-020-01500-2Acute lung injuryFerroptosisNrf2DrowningSeawater |
| spellingShingle | Yu-bao Qiu Bin-bin Wan Gang Liu Ya-xian Wu Dan Chen Mu-dan Lu Jun-liang Chen Ren-qiang Yu Dao-zhen Chen Qing-feng Pang Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis Respiratory Research Acute lung injury Ferroptosis Nrf2 Drowning Seawater |
| title | Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis |
| title_full | Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis |
| title_fullStr | Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis |
| title_full_unstemmed | Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis |
| title_short | Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis |
| title_sort | nrf2 protects against seawater drowning induced acute lung injury via inhibiting ferroptosis |
| topic | Acute lung injury Ferroptosis Nrf2 Drowning Seawater |
| url | http://link.springer.com/article/10.1186/s12931-020-01500-2 |
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