SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microglia
Manganese (Mn), as one of the environmental risk factors for Parkinson’s disease (PD), has been widely studied. Though autophagy dysfunction and neuroinflammation mainly are responsible for the causative issue of Mn neurotoxicity, the molecular mechanism of parkinsonism caused by Mn has not been exp...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323003767 |
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| author | Dongying Yan Yuqing Yang Jing Lang Xiaobai Wang Ying Huang Jia Meng Jie Wu Xinning Zeng Hong Li Honglin Ma Liang Gao |
| author_facet | Dongying Yan Yuqing Yang Jing Lang Xiaobai Wang Ying Huang Jia Meng Jie Wu Xinning Zeng Hong Li Honglin Ma Liang Gao |
| author_sort | Dongying Yan |
| collection | DOAJ |
| description | Manganese (Mn), as one of the environmental risk factors for Parkinson’s disease (PD), has been widely studied. Though autophagy dysfunction and neuroinflammation mainly are responsible for the causative issue of Mn neurotoxicity, the molecular mechanism of parkinsonism caused by Mn has not been explored clearly. The results of in vivo and in vitro experiments showed that overexposure to Mn caused neuroinflammation impairment and autophagy dysfunction, accompanied by the increase of IL-1β, IL-6, and TNF-α mRNA expression, and nerve cell apoptosis, microglia cell activation, NF-κB activation, poor neurobehavior performance. This is due to Mn-induced the downregulation of SIRT1. Upregulation of SIRT1 in vivo and in vitro could alleviate Mn-induced autophagy dysfunction and neuroinflammation, yet these beneficial effects were abolished following 3-MA administration. Furthermore, we found that Mn interfered with the acetylation of FOXO3 by SIRT1 in BV2 cells, leading to a decrease in the nuclear translocation of FOXO3, and its binding of LC3B promoter and transcription activity. This could be antagonized by the upregulation of SIRT1. Finally, it is proved that SIRT1/FOXO3-LC3B autophagy signaling involves in Mn-induced neuroinflammation impairment. |
| first_indexed | 2024-04-09T16:17:24Z |
| format | Article |
| id | doaj.art-c53832134f6d40c4aca34b9d2a72fb93 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-09T16:17:24Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-c53832134f6d40c4aca34b9d2a72fb932023-04-24T04:37:22ZengElsevierEcotoxicology and Environmental Safety0147-65132023-05-01256114872SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microgliaDongying Yan0Yuqing Yang1Jing Lang2Xiaobai Wang3Ying Huang4Jia Meng5Jie Wu6Xinning Zeng7Hong Li8Honglin Ma9Liang Gao10School of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, China; Preventive Medicine Experimental Practice Teaching Center, School of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, China; Preventive Medicine Experimental Practice Teaching Center, School of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, ChinaSchool of Public Health, Jinzhou Medical University, Section III, Linghe District, Jinzhou, China; Corresponding author.Manganese (Mn), as one of the environmental risk factors for Parkinson’s disease (PD), has been widely studied. Though autophagy dysfunction and neuroinflammation mainly are responsible for the causative issue of Mn neurotoxicity, the molecular mechanism of parkinsonism caused by Mn has not been explored clearly. The results of in vivo and in vitro experiments showed that overexposure to Mn caused neuroinflammation impairment and autophagy dysfunction, accompanied by the increase of IL-1β, IL-6, and TNF-α mRNA expression, and nerve cell apoptosis, microglia cell activation, NF-κB activation, poor neurobehavior performance. This is due to Mn-induced the downregulation of SIRT1. Upregulation of SIRT1 in vivo and in vitro could alleviate Mn-induced autophagy dysfunction and neuroinflammation, yet these beneficial effects were abolished following 3-MA administration. Furthermore, we found that Mn interfered with the acetylation of FOXO3 by SIRT1 in BV2 cells, leading to a decrease in the nuclear translocation of FOXO3, and its binding of LC3B promoter and transcription activity. This could be antagonized by the upregulation of SIRT1. Finally, it is proved that SIRT1/FOXO3-LC3B autophagy signaling involves in Mn-induced neuroinflammation impairment.http://www.sciencedirect.com/science/article/pii/S0147651323003767ManganeseNeuroinflammationAutophagySilent information regulator 1Forkhead box O3 |
| spellingShingle | Dongying Yan Yuqing Yang Jing Lang Xiaobai Wang Ying Huang Jia Meng Jie Wu Xinning Zeng Hong Li Honglin Ma Liang Gao SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microglia Ecotoxicology and Environmental Safety Manganese Neuroinflammation Autophagy Silent information regulator 1 Forkhead box O3 |
| title | SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microglia |
| title_full | SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microglia |
| title_fullStr | SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microglia |
| title_full_unstemmed | SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microglia |
| title_short | SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microglia |
| title_sort | sirt1 foxo3 mediated autophagy signaling involved in manganese induced neuroinflammation in microglia |
| topic | Manganese Neuroinflammation Autophagy Silent information regulator 1 Forkhead box O3 |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323003767 |
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