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Antioxidant mitoquinone ameliorates EtOH-LPS induced lung injury by inhibiting mitophagy and NLRP3 inflammasome activation
Chronic ethanol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). However, the mechanisms involved are unknown. One explanation is that ethanol produces damaging reactive oxygen species (ROS) and disturbs t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436256/ https://www.ncbi.nlm.nih.gov/pubmed/36059543 http://dx.doi.org/10.3389/fimmu.2022.973108 |
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author | Sang, Wenhua Chen, Sha Lin, Lidan Wang, Nan Kong, Xiaoxia Ye, Jinyan |
author_facet | Sang, Wenhua Chen, Sha Lin, Lidan Wang, Nan Kong, Xiaoxia Ye, Jinyan |
author_sort | Sang, Wenhua |
collection | PubMed |
description | Chronic ethanol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). However, the mechanisms involved are unknown. One explanation is that ethanol produces damaging reactive oxygen species (ROS) and disturbs the balance of mitochondria within the lungs to promote a pro-injury environment. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate EtOH-LPS-induced lung injury. To test this, we investigated the effects of mitochondria-targeted ubiquinone, Mitoquinone (MitoQ) on ethanol-sensitized lung injury induced by LPS. Lung inflammation, ROS, mitochondria function, and mitophagy were assessed. We demonstrated that chronic ethanol feeding sensitized the lung to LPS-induced lung injury with significantly increased reactive oxygen species ROS level and mitochondrial injury as well as lung cellular NLRP3 inflammasome activation. These deleterious effects were attenuated by MitoQ administration in mice. The protective effects of MitoQ are associated with decreased cellular mitophagy and NLRP3 inflammasome activation in vivo and in vitro. Taken together, our results demonstrated that ethanol aggravated LPS-induced lung injury, and antioxidant MitoQ protects from EtOH-LPS-induced lung injury, probably through reducing mitophagy and protecting mitochondria, followed by NLRP3 inflammasome activation. These results will provide the prevention and treatment of ethanol intake effects with new ideas. |
format | Online Article Text |
id | pubmed-9436256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94362562022-09-02 Antioxidant mitoquinone ameliorates EtOH-LPS induced lung injury by inhibiting mitophagy and NLRP3 inflammasome activation Sang, Wenhua Chen, Sha Lin, Lidan Wang, Nan Kong, Xiaoxia Ye, Jinyan Front Immunol Immunology Chronic ethanol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). However, the mechanisms involved are unknown. One explanation is that ethanol produces damaging reactive oxygen species (ROS) and disturbs the balance of mitochondria within the lungs to promote a pro-injury environment. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate EtOH-LPS-induced lung injury. To test this, we investigated the effects of mitochondria-targeted ubiquinone, Mitoquinone (MitoQ) on ethanol-sensitized lung injury induced by LPS. Lung inflammation, ROS, mitochondria function, and mitophagy were assessed. We demonstrated that chronic ethanol feeding sensitized the lung to LPS-induced lung injury with significantly increased reactive oxygen species ROS level and mitochondrial injury as well as lung cellular NLRP3 inflammasome activation. These deleterious effects were attenuated by MitoQ administration in mice. The protective effects of MitoQ are associated with decreased cellular mitophagy and NLRP3 inflammasome activation in vivo and in vitro. Taken together, our results demonstrated that ethanol aggravated LPS-induced lung injury, and antioxidant MitoQ protects from EtOH-LPS-induced lung injury, probably through reducing mitophagy and protecting mitochondria, followed by NLRP3 inflammasome activation. These results will provide the prevention and treatment of ethanol intake effects with new ideas. Frontiers Media S.A. 2022-08-18 /pmc/articles/PMC9436256/ /pubmed/36059543 http://dx.doi.org/10.3389/fimmu.2022.973108 Text en Copyright © 2022 Sang, Chen, Lin, Wang, Kong and Ye https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Sang, Wenhua Chen, Sha Lin, Lidan Wang, Nan Kong, Xiaoxia Ye, Jinyan Antioxidant mitoquinone ameliorates EtOH-LPS induced lung injury by inhibiting mitophagy and NLRP3 inflammasome activation |
title | Antioxidant mitoquinone ameliorates EtOH-LPS induced lung injury by inhibiting mitophagy and NLRP3 inflammasome activation |
title_full | Antioxidant mitoquinone ameliorates EtOH-LPS induced lung injury by inhibiting mitophagy and NLRP3 inflammasome activation |
title_fullStr | Antioxidant mitoquinone ameliorates EtOH-LPS induced lung injury by inhibiting mitophagy and NLRP3 inflammasome activation |
title_full_unstemmed | Antioxidant mitoquinone ameliorates EtOH-LPS induced lung injury by inhibiting mitophagy and NLRP3 inflammasome activation |
title_short | Antioxidant mitoquinone ameliorates EtOH-LPS induced lung injury by inhibiting mitophagy and NLRP3 inflammasome activation |
title_sort | antioxidant mitoquinone ameliorates etoh-lps induced lung injury by inhibiting mitophagy and nlrp3 inflammasome activation |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436256/ https://www.ncbi.nlm.nih.gov/pubmed/36059543 http://dx.doi.org/10.3389/fimmu.2022.973108 |
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