Mitophagy protects against silver nanoparticle–induced hepatotoxicity by inhibiting mitochondrial ROS and the NLRP3 inflammasome
Silver nanoparticles (AgNPs) have wide clinical applications because of their excellent antibacterial properties; however, they can cause liver inflammation in animals. Macrophages are among the main cells mediating inflammation and are also responsible for the phagocytosis of nanomaterials. The NLR...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324002124 |
| _version_ | 1797261842333040640 |
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| author | Jiangyan Li Ming Li Ruirui Wang Jiaqi Lan Lian Yu Jie Gao Hezuo Lü Qiang Fang Fengchao Wang |
| author_facet | Jiangyan Li Ming Li Ruirui Wang Jiaqi Lan Lian Yu Jie Gao Hezuo Lü Qiang Fang Fengchao Wang |
| author_sort | Jiangyan Li |
| collection | DOAJ |
| description | Silver nanoparticles (AgNPs) have wide clinical applications because of their excellent antibacterial properties; however, they can cause liver inflammation in animals. Macrophages are among the main cells mediating inflammation and are also responsible for the phagocytosis of nanomaterials. The NLRP3 inflammasome is a major mechanism of inflammation, and its activation both induces cytokine release and triggers inflammatory cell death (i.e., pyroptosis). In previous studies, we demonstrated that mitophagy activation plays a protective role against AgNP-induced hepatotoxicity. However, the exact molecular mechanisms underlying these processes are not fully understood. In this study, we demonstrate that AgNP exposure induces NLRP3 inflammasome activation, mitochondrial damage and pyroptosis in vivo and in vitro. NLRP3 silencing or inhibiting mitochondrial reactive oxygen species (ROS) overproduction reduces PINK1-Parkin-mediated mitophagy. Meanwhile, the inhibition of mitophagy ROS production, mitochondrial, NLRP3-mediated inflammation, and pyroptosis in RAW264.7 cells were more pronounced than in the control group. These results suggest that PINK1-Parkin-mediated mitophagy plays a protective role by reducing AgNP-induced mitochondrial ROS and subsequent NLRP3 inflammasome activation. |
| first_indexed | 2024-03-07T20:06:03Z |
| format | Article |
| id | doaj.art-732a40cbcd98434ea89f63e26885c029 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-24T23:47:38Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-732a40cbcd98434ea89f63e26885c0292024-03-15T04:42:49ZengElsevierEcotoxicology and Environmental Safety0147-65132024-03-01273116137Mitophagy protects against silver nanoparticle–induced hepatotoxicity by inhibiting mitochondrial ROS and the NLRP3 inflammasomeJiangyan Li0Ming Li1Ruirui Wang2Jiaqi Lan3Lian Yu4Jie Gao5Hezuo Lü6Qiang Fang7Fengchao Wang8Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui Province 233030, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, ChinaBengbu Medical University, Bengbu, Anhui Province 233030, ChinaBengbu Medical University, Bengbu, Anhui Province 233030, ChinaBengbu Medical University, Bengbu, Anhui Province 233030, ChinaBengbu Medical University, Bengbu, Anhui Province 233030, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui Province 233030, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui Province 233030, ChinaBengbu Medical University, Bengbu, Anhui Province 233030, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui Province 233030, China; Corresponding author.Silver nanoparticles (AgNPs) have wide clinical applications because of their excellent antibacterial properties; however, they can cause liver inflammation in animals. Macrophages are among the main cells mediating inflammation and are also responsible for the phagocytosis of nanomaterials. The NLRP3 inflammasome is a major mechanism of inflammation, and its activation both induces cytokine release and triggers inflammatory cell death (i.e., pyroptosis). In previous studies, we demonstrated that mitophagy activation plays a protective role against AgNP-induced hepatotoxicity. However, the exact molecular mechanisms underlying these processes are not fully understood. In this study, we demonstrate that AgNP exposure induces NLRP3 inflammasome activation, mitochondrial damage and pyroptosis in vivo and in vitro. NLRP3 silencing or inhibiting mitochondrial reactive oxygen species (ROS) overproduction reduces PINK1-Parkin-mediated mitophagy. Meanwhile, the inhibition of mitophagy ROS production, mitochondrial, NLRP3-mediated inflammation, and pyroptosis in RAW264.7 cells were more pronounced than in the control group. These results suggest that PINK1-Parkin-mediated mitophagy plays a protective role by reducing AgNP-induced mitochondrial ROS and subsequent NLRP3 inflammasome activation.http://www.sciencedirect.com/science/article/pii/S0147651324002124Silver nanoparticlesNLRP3 inflammasomeMitophagyMitochondrial reactive oxygen speciesPyroptosis |
| spellingShingle | Jiangyan Li Ming Li Ruirui Wang Jiaqi Lan Lian Yu Jie Gao Hezuo Lü Qiang Fang Fengchao Wang Mitophagy protects against silver nanoparticle–induced hepatotoxicity by inhibiting mitochondrial ROS and the NLRP3 inflammasome Ecotoxicology and Environmental Safety Silver nanoparticles NLRP3 inflammasome Mitophagy Mitochondrial reactive oxygen species Pyroptosis |
| title | Mitophagy protects against silver nanoparticle–induced hepatotoxicity by inhibiting mitochondrial ROS and the NLRP3 inflammasome |
| title_full | Mitophagy protects against silver nanoparticle–induced hepatotoxicity by inhibiting mitochondrial ROS and the NLRP3 inflammasome |
| title_fullStr | Mitophagy protects against silver nanoparticle–induced hepatotoxicity by inhibiting mitochondrial ROS and the NLRP3 inflammasome |
| title_full_unstemmed | Mitophagy protects against silver nanoparticle–induced hepatotoxicity by inhibiting mitochondrial ROS and the NLRP3 inflammasome |
| title_short | Mitophagy protects against silver nanoparticle–induced hepatotoxicity by inhibiting mitochondrial ROS and the NLRP3 inflammasome |
| title_sort | mitophagy protects against silver nanoparticle induced hepatotoxicity by inhibiting mitochondrial ros and the nlrp3 inflammasome |
| topic | Silver nanoparticles NLRP3 inflammasome Mitophagy Mitochondrial reactive oxygen species Pyroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324002124 |
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