Qi Liu, Jiali Weng, Chenfei Li, Yi Feng, Meiqin Xie, Xiaohui Wang, Qing Chang, Mengnan Li, Kian Fan Chung, Ian M Adcock, Yan Huang, Hai Zhang, Feng Li
{"title":"通过调节线粒体裂变和融合减轻 PM2.5 诱导的肺泡上皮细胞和肺损伤。","authors":"Qi Liu, Jiali Weng, Chenfei Li, Yi Feng, Meiqin Xie, Xiaohui Wang, Qing Chang, Mengnan Li, Kian Fan Chung, Ian M Adcock, Yan Huang, Hai Zhang, Feng Li","doi":"10.1186/s12989-023-00534-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM<sub>2.5</sub>) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in health and disease. We examined the role of mitochondrial fission and fusion in PM<sub>2.5</sub>-induced alveolar epithelial cell damage and lung injury. Key genes in these processes include dystrophin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) respectively.</p><p><strong>Methods: </strong>Alveolar epithelial (A549) cells were treated with PM<sub>2.5</sub> (32 µg/ml) in the presence and absence of Mdivi-1 (10µM, a DRP1 inhibitor) or BGP-15 (10µM, an OPA1 activator). Results were validated using DRP1-knockdown (KD) and OPA1-overexpression (OE). Mice were injected intraperitoneally with Mdivi-1 (20 mg/kg), BGP-15 (20 mg/kg) or distilled water (control) one hour before intranasal instillation of PM<sub>2.5</sub> (7.8 mg/kg) or distilled water for two consecutive days.</p><p><strong>Results: </strong>PM<sub>2.5</sub> exposure of A549 cells caused oxidative stress, enhanced inflammation, necroptosis, mitophagy and mitochondrial dysfunction indicated by abnormal mitochondrial morphology, decreased mitochondrial membrane potential (ΔΨm), reduced mitochondrial respiration and disrupted mitochondrial fission and fusion. Regulating mitochondrial fission and fusion pharmacologically using Mdivi-1 and BGP-15 and genetically using DRP1-KD and OPA1-OE prevented PM<sub>2.5</sub>-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM<sub>2.5</sub>-induced acute lung injury in mice.</p><p><strong>Conclusion: </strong>Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM<sub>2.5</sub>-induced alveolar epithelial cell damage in vitro and lung injury in vivo.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":null,"pages":null},"PeriodicalIF":7.2000,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353144/pdf/","citationCount":"2","resultStr":"{\"title\":\"Attenuation of PM<sub>2.5</sub>-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion.\",\"authors\":\"Qi Liu, Jiali Weng, Chenfei Li, Yi Feng, Meiqin Xie, Xiaohui Wang, Qing Chang, Mengnan Li, Kian Fan Chung, Ian M Adcock, Yan Huang, Hai Zhang, Feng Li\",\"doi\":\"10.1186/s12989-023-00534-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM<sub>2.5</sub>) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in health and disease. We examined the role of mitochondrial fission and fusion in PM<sub>2.5</sub>-induced alveolar epithelial cell damage and lung injury. Key genes in these processes include dystrophin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) respectively.</p><p><strong>Methods: </strong>Alveolar epithelial (A549) cells were treated with PM<sub>2.5</sub> (32 µg/ml) in the presence and absence of Mdivi-1 (10µM, a DRP1 inhibitor) or BGP-15 (10µM, an OPA1 activator). Results were validated using DRP1-knockdown (KD) and OPA1-overexpression (OE). Mice were injected intraperitoneally with Mdivi-1 (20 mg/kg), BGP-15 (20 mg/kg) or distilled water (control) one hour before intranasal instillation of PM<sub>2.5</sub> (7.8 mg/kg) or distilled water for two consecutive days.</p><p><strong>Results: </strong>PM<sub>2.5</sub> exposure of A549 cells caused oxidative stress, enhanced inflammation, necroptosis, mitophagy and mitochondrial dysfunction indicated by abnormal mitochondrial morphology, decreased mitochondrial membrane potential (ΔΨm), reduced mitochondrial respiration and disrupted mitochondrial fission and fusion. Regulating mitochondrial fission and fusion pharmacologically using Mdivi-1 and BGP-15 and genetically using DRP1-KD and OPA1-OE prevented PM<sub>2.5</sub>-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM<sub>2.5</sub>-induced acute lung injury in mice.</p><p><strong>Conclusion: </strong>Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM<sub>2.5</sub>-induced alveolar epithelial cell damage in vitro and lung injury in vivo.</p>\",\"PeriodicalId\":19847,\"journal\":{\"name\":\"Particle and Fibre Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.2000,\"publicationDate\":\"2023-07-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353144/pdf/\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Particle and Fibre Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12989-023-00534-w\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Particle and Fibre Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12989-023-00534-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion.
Background: Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM2.5) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in health and disease. We examined the role of mitochondrial fission and fusion in PM2.5-induced alveolar epithelial cell damage and lung injury. Key genes in these processes include dystrophin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) respectively.
Methods: Alveolar epithelial (A549) cells were treated with PM2.5 (32 µg/ml) in the presence and absence of Mdivi-1 (10µM, a DRP1 inhibitor) or BGP-15 (10µM, an OPA1 activator). Results were validated using DRP1-knockdown (KD) and OPA1-overexpression (OE). Mice were injected intraperitoneally with Mdivi-1 (20 mg/kg), BGP-15 (20 mg/kg) or distilled water (control) one hour before intranasal instillation of PM2.5 (7.8 mg/kg) or distilled water for two consecutive days.
Results: PM2.5 exposure of A549 cells caused oxidative stress, enhanced inflammation, necroptosis, mitophagy and mitochondrial dysfunction indicated by abnormal mitochondrial morphology, decreased mitochondrial membrane potential (ΔΨm), reduced mitochondrial respiration and disrupted mitochondrial fission and fusion. Regulating mitochondrial fission and fusion pharmacologically using Mdivi-1 and BGP-15 and genetically using DRP1-KD and OPA1-OE prevented PM2.5-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM2.5-induced acute lung injury in mice.
Conclusion: Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM2.5-induced alveolar epithelial cell damage in vitro and lung injury in vivo.
期刊介绍:
Particle and Fibre Toxicology is an online journal that is open access and peer-reviewed. It covers a range of disciplines such as material science, biomaterials, and nanomedicine, focusing on the toxicological effects of particles and fibres. The journal serves as a platform for scientific debate and communication among toxicologists and scientists from different fields who work with particle and fibre materials. The main objective of the journal is to deepen our understanding of the physico-chemical properties of particles, their potential for human exposure, and the resulting biological effects. It also addresses regulatory issues related to particle exposure in workplaces and the general environment. Moreover, the journal recognizes that there are various situations where particles can pose a toxicological threat, such as the use of old materials in new applications or the introduction of new materials altogether. By encompassing all these disciplines, Particle and Fibre Toxicology provides a comprehensive source for research in this field.