Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome
Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood–brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative disease...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412024002174 |
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| author | Xinyue Li Kai Ma Tiantian Tian Huan Pang Tianxiang Liu Meng Li Jiali Li Zhixuan Luo Huiyuan Hu Shanshan Hou Jing Yu Qiaohong Hou Xiuling Song Chao Zhao Haiying Du Jinhua Li Zhongjun Du Minghua Jin |
| author_facet | Xinyue Li Kai Ma Tiantian Tian Huan Pang Tianxiang Liu Meng Li Jiali Li Zhixuan Luo Huiyuan Hu Shanshan Hou Jing Yu Qiaohong Hou Xiuling Song Chao Zhao Haiying Du Jinhua Li Zhongjun Du Minghua Jin |
| author_sort | Xinyue Li |
| collection | DOAJ |
| description | Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood–brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress. |
| first_indexed | 2024-04-24T12:31:41Z |
| format | Article |
| id | doaj.art-57cfa09c89cd4fce8c134b3db6951959 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-24T12:31:41Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-57cfa09c89cd4fce8c134b3db69519592024-04-08T04:08:09ZengElsevierEnvironment International0160-41202024-04-01186108631Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasomeXinyue Li0Kai Ma1Tiantian Tian2Huan Pang3Tianxiang Liu4Meng Li5Jiali Li6Zhixuan Luo7Huiyuan Hu8Shanshan Hou9Jing Yu10Qiaohong Hou11Xiuling Song12Chao Zhao13Haiying Du14Jinhua Li15Zhongjun Du16Minghua Jin17School of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR ChinaSchool of Public Health Jilin University, Changchun, Jilin,130021, PR China; Corresponding authors.Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250062, PR China; Corresponding authors.School of Public Health Jilin University, Changchun, Jilin,130021, PR China; Corresponding authors.Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood–brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress.http://www.sciencedirect.com/science/article/pii/S0160412024002174Methylmercury (MeHg)Microgliareactive oxygen species (ROS)NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasomeInflammationAutophagy |
| spellingShingle | Xinyue Li Kai Ma Tiantian Tian Huan Pang Tianxiang Liu Meng Li Jiali Li Zhixuan Luo Huiyuan Hu Shanshan Hou Jing Yu Qiaohong Hou Xiuling Song Chao Zhao Haiying Du Jinhua Li Zhongjun Du Minghua Jin Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome Environment International Methylmercury (MeHg) Microglia reactive oxygen species (ROS) NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome Inflammation Autophagy |
| title | Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome |
| title_full | Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome |
| title_fullStr | Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome |
| title_full_unstemmed | Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome |
| title_short | Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome |
| title_sort | methylmercury induces inflammatory response and autophagy in microglia through the activation of nlrp3 inflammasome |
| topic | Methylmercury (MeHg) Microglia reactive oxygen species (ROS) NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome Inflammation Autophagy |
| url | http://www.sciencedirect.com/science/article/pii/S0160412024002174 |
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