Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in cortex
Arsenite is a toxic metalloid that causes various adverse effects in brain. However, the underlying mechanisms of arsenite-induced neurotoxicity remain poorly understood. In this study, both adult beclin 1+/+ and beclin 1+/- mice were employed to establish a model of chronic arsenite exposure by tre...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651321011787 |
| _version_ | 1831643520358678528 |
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| author | Hongmei Zhou Hong Ling Yunlong Li Xuejun Jiang Shuqun Cheng Golamaully Mohammad Zubeir Yinyin Xia Xia Qin Jun Zhang Zhen Zou Chengzhi Chen |
| author_facet | Hongmei Zhou Hong Ling Yunlong Li Xuejun Jiang Shuqun Cheng Golamaully Mohammad Zubeir Yinyin Xia Xia Qin Jun Zhang Zhen Zou Chengzhi Chen |
| author_sort | Hongmei Zhou |
| collection | DOAJ |
| description | Arsenite is a toxic metalloid that causes various adverse effects in brain. However, the underlying mechanisms of arsenite-induced neurotoxicity remain poorly understood. In this study, both adult beclin 1+/+ and beclin 1+/- mice were employed to establish a model of chronic arsenite exposure by treating with arsenite via drinking water for 6 months. The results clearly demonstrated that exposure of arsenite profoundly caused damage to the cerebral cortex, induced autophagy and impaired autophagic flux in the cerebral cortex. Heterozygous disruption of beclin 1 in animals remarkably alleviated the neurotoxic effects of arsenite. To verify the results obtained in the animals, a permanent U251 cell line was used. After treating of cells with arsenite, similar phenomenon was also observed, showing the significant elevation in the expression levels of autophagy-related genes. Importantly, lysosomal dysfunction caused by arsenite was observed in vitro and in vivo. Either knockdown of beclin in cells or heterozygous disruption of beclin 1 in animals remarkably alleviated the lysosomal dysfunction induced by arsenite. These findings indicate that downregulation of beclin 1 could restore arsenite-induced impaired autophagic flux possibly through improving lysosomal function, and suggesting that regulation of autophagy via beclin 1 would be an alternative approach for the treatment of arsenite neurotoxicity. |
| first_indexed | 2024-12-19T13:01:40Z |
| format | Article |
| id | doaj.art-58735fc14b984825b6f31a8a2bd170f7 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-19T13:01:40Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-58735fc14b984825b6f31a8a2bd170f72022-12-21T20:20:14ZengElsevierEcotoxicology and Environmental Safety0147-65132022-01-01229113066Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in cortexHongmei Zhou0Hong Ling1Yunlong Li2Xuejun Jiang3Shuqun Cheng4Golamaully Mohammad Zubeir5Yinyin Xia6Xia Qin7Jun Zhang8Zhen Zou9Chengzhi Chen10Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaDepartment of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaDepartment of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaCenter of Experimental Teaching for Public Health, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaDepartment of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaDepartment of Food Engineering, Ankara University, Ankara 06100,TurkeyDepartment of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaDepartment of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaMolecular Biology Laboratory of Respiratory Diseases, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaMolecular Biology Laboratory of Respiratory Diseases, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, People’s Republic of China; Dongsheng Lung-Brain Disease Joint Lab, Chongqing Medical University, Chongqing 400016, People’s Republic of China; Corresponding authors at: Molecular Biology Laboratory of Respiratory Diseases, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, People’s Republic of China.Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of China; Dongsheng Lung-Brain Disease Joint Lab, Chongqing Medical University, Chongqing 400016, People’s Republic of China; Corresponding authors at: Molecular Biology Laboratory of Respiratory Diseases, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, People’s Republic of China.Arsenite is a toxic metalloid that causes various adverse effects in brain. However, the underlying mechanisms of arsenite-induced neurotoxicity remain poorly understood. In this study, both adult beclin 1+/+ and beclin 1+/- mice were employed to establish a model of chronic arsenite exposure by treating with arsenite via drinking water for 6 months. The results clearly demonstrated that exposure of arsenite profoundly caused damage to the cerebral cortex, induced autophagy and impaired autophagic flux in the cerebral cortex. Heterozygous disruption of beclin 1 in animals remarkably alleviated the neurotoxic effects of arsenite. To verify the results obtained in the animals, a permanent U251 cell line was used. After treating of cells with arsenite, similar phenomenon was also observed, showing the significant elevation in the expression levels of autophagy-related genes. Importantly, lysosomal dysfunction caused by arsenite was observed in vitro and in vivo. Either knockdown of beclin in cells or heterozygous disruption of beclin 1 in animals remarkably alleviated the lysosomal dysfunction induced by arsenite. These findings indicate that downregulation of beclin 1 could restore arsenite-induced impaired autophagic flux possibly through improving lysosomal function, and suggesting that regulation of autophagy via beclin 1 would be an alternative approach for the treatment of arsenite neurotoxicity.http://www.sciencedirect.com/science/article/pii/S0147651321011787ArseniteBeclin 1AutophagyLysosomal dysfunctionNeurotoxicity |
| spellingShingle | Hongmei Zhou Hong Ling Yunlong Li Xuejun Jiang Shuqun Cheng Golamaully Mohammad Zubeir Yinyin Xia Xia Qin Jun Zhang Zhen Zou Chengzhi Chen Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in cortex Ecotoxicology and Environmental Safety Arsenite Beclin 1 Autophagy Lysosomal dysfunction Neurotoxicity |
| title | Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in cortex |
| title_full | Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in cortex |
| title_fullStr | Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in cortex |
| title_full_unstemmed | Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in cortex |
| title_short | Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in cortex |
| title_sort | downregulation of beclin 1 restores arsenite induced impaired autophagic flux by improving the lysosomal function in cortex |
| topic | Arsenite Beclin 1 Autophagy Lysosomal dysfunction Neurotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S0147651321011787 |
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