Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells
With the increasing use of silver nanoparticles (AgNPs) in biological materials, the cytotoxicity caused by these particles has attracted much attention. However, the molecular mechanism underlying AgNP cytotoxicity remains unclear. In this study, we aimed to systematically investigate the toxicity...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651320313002 |
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| author | Jiangyan Li Xiaoru Chang Mengting Shang Shuyan Niu Wenli Zhang Bangyong Zhang Wenyan Huang Tianshu Wu Ting Zhang Meng Tang Yuying Xue |
| author_facet | Jiangyan Li Xiaoru Chang Mengting Shang Shuyan Niu Wenli Zhang Bangyong Zhang Wenyan Huang Tianshu Wu Ting Zhang Meng Tang Yuying Xue |
| author_sort | Jiangyan Li |
| collection | DOAJ |
| description | With the increasing use of silver nanoparticles (AgNPs) in biological materials, the cytotoxicity caused by these particles has attracted much attention. However, the molecular mechanism underlying AgNP cytotoxicity remains unclear. In this study, we aimed to systematically investigate the toxicity induced by AgNP exposure to the lung adenocarcinoma A549 cell line at the subcellular and signaling pathway levels and elucidate the related molecular mechanism. The survival rate of cells exposed to AgNPs at 0, 20, 40, 80, and 160 μg/mL for 24 or 48 h decreased in a dose- and time-dependent manner. AgNPs induced autophagy and mitophagy, determined by the transmission electron microscopy investigation and upregulation of LC3 II/I, p62, PINK1, and Parkin expression levels. AgNP treatment induced lysosomal injury, including the decline of lysosomal membrane integrity and increase in cathepsin B level. The decreased in mitochondrial membrane potential, along with upregulation of cytochrome c, caspases 9 and 3, and BAX/BCL2, further suggested that mitochondrial injury were involved in AgNP-induced apoptosis. In addition, mitochondrial injury may further lead to excessive production of reactive oxygen species and oxidative/ antioxidant imbalance. The results suggested that AgNPs could regulate autophagy via mitochondrial and lysosome injury in A549 cells. The information of the molecular mechanism will provide an experimental basis for the safe application of nanomaterials. |
| first_indexed | 2024-12-13T12:59:52Z |
| format | Article |
| id | doaj.art-dfd534b29f5241998d3044cf12302b56 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-13T12:59:52Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-dfd534b29f5241998d3044cf12302b562022-12-21T23:45:05ZengElsevierEcotoxicology and Environmental Safety0147-65132021-01-01208111463Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cellsJiangyan Li0Xiaoru Chang1Mengting Shang2Shuyan Niu3Wenli Zhang4Bangyong Zhang5Wenyan Huang6Tianshu Wu7Ting Zhang8Meng Tang9Yuying Xue10Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaKey Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaCorresponding author.; Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaWith the increasing use of silver nanoparticles (AgNPs) in biological materials, the cytotoxicity caused by these particles has attracted much attention. However, the molecular mechanism underlying AgNP cytotoxicity remains unclear. In this study, we aimed to systematically investigate the toxicity induced by AgNP exposure to the lung adenocarcinoma A549 cell line at the subcellular and signaling pathway levels and elucidate the related molecular mechanism. The survival rate of cells exposed to AgNPs at 0, 20, 40, 80, and 160 μg/mL for 24 or 48 h decreased in a dose- and time-dependent manner. AgNPs induced autophagy and mitophagy, determined by the transmission electron microscopy investigation and upregulation of LC3 II/I, p62, PINK1, and Parkin expression levels. AgNP treatment induced lysosomal injury, including the decline of lysosomal membrane integrity and increase in cathepsin B level. The decreased in mitochondrial membrane potential, along with upregulation of cytochrome c, caspases 9 and 3, and BAX/BCL2, further suggested that mitochondrial injury were involved in AgNP-induced apoptosis. In addition, mitochondrial injury may further lead to excessive production of reactive oxygen species and oxidative/ antioxidant imbalance. The results suggested that AgNPs could regulate autophagy via mitochondrial and lysosome injury in A549 cells. The information of the molecular mechanism will provide an experimental basis for the safe application of nanomaterials.http://www.sciencedirect.com/science/article/pii/S0147651320313002Silver nanoparticleMitochondriaAutophagyLysosomalApoptosis |
| spellingShingle | Jiangyan Li Xiaoru Chang Mengting Shang Shuyan Niu Wenli Zhang Bangyong Zhang Wenyan Huang Tianshu Wu Ting Zhang Meng Tang Yuying Xue Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells Ecotoxicology and Environmental Safety Silver nanoparticle Mitochondria Autophagy Lysosomal Apoptosis |
| title | Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells |
| title_full | Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells |
| title_fullStr | Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells |
| title_full_unstemmed | Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells |
| title_short | Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells |
| title_sort | mitophagy lysosomal pathway is involved in silver nanoparticle induced apoptosis in a549 cells |
| topic | Silver nanoparticle Mitochondria Autophagy Lysosomal Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651320313002 |
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