دورية أكاديمية
Polystyrene nanoplastics induce lipophagy via the AMPK/ULK1 pathway and block lipophagic flux leading to lipid accumulation in hepatocytes.
| العنوان: | Polystyrene nanoplastics induce lipophagy via the AMPK/ULK1 pathway and block lipophagic flux leading to lipid accumulation in hepatocytes. |
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| المؤلفون: | Fan Z; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Zhang Y; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Shanxi Provincial Center for Disease Control and Prevention, Taiyuan 030012, Shanxi, China., Fang Y; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Zhong H; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China., Wei T; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Akhtar H; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Zhang J; Center for Clinical Laboratory, Capital Medical University, Beijing 100069, China., Yang M; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Li Y; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Zhou X; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Sun Z; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China., Wang J; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: wangji@ccmu.edu.cn. |
| المصدر: | Journal of hazardous materials [J Hazard Mater] 2024 Sep 05; Vol. 476, pp. 134878. Date of Electronic Publication: 2024 Jun 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9422688 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3336 (Electronic) Linking ISSN: 03043894 NLM ISO Abbreviation: J Hazard Mater Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier, |
| مواضيع طبية MeSH: | Hepatocytes*/drug effects , Hepatocytes*/metabolism , Polystyrenes*/toxicity , Autophagy-Related Protein-1 Homolog*/metabolism , Autophagy*/drug effects , Lipid Metabolism*/drug effects , AMP-Activated Protein Kinases*/metabolism, Humans ; Lipid Droplets/metabolism ; Lipid Droplets/drug effects ; Nanoparticles/toxicity ; Signal Transduction/drug effects ; Microplastics/toxicity ; Hep G2 Cells ; Intracellular Signaling Peptides and Proteins/metabolism ; Cell Survival/drug effects |
| مستخلص: | Micro- and nanoplastic pollution has emerged as a significant global concern due to their extensive presence in the environment and potential adverse effects on human health. Nanoplastics can enter the human circulatory system and accumulate in the liver, disrupting hepatic metabolism and causing hepatotoxicity. However, the precise mechanism remains uncertain. Lipophagy is an alternative mechanism of lipid metabolism involving autophagy. This study aims to explore how polystyrene nanoplastics (PSNPs) influence lipid metabolism in hepatocytes via lipophagy. Initially, it was found that PSNPs were internalized by human hepatocytes, resulting in decreased cell viability. PSNPs were found to induce the accumulation of lipid droplets (LDs), with autophagy inhibition exacerbating this accumulation. Then, PSNPs were proved to activate lipophagy by recruiting LDs into autophagosomes and block the lipophagic flux by impairing lysosomal function, inhibiting LD degradation. Ultimately, PSNPs were shown to activate lipophagy through the AMPK/ULK1 pathway, and knocking down AMPK exacerbated lipid accumulation in hepatocytes. Overall, these results indicated that PSNPs triggered lipophagy via the AMPK/ULK1 pathway and blocked lipophagic flux, leading to lipid accumulation in hepatocytes. Thus, this study identifies a novel mechanism underlying nanoplastic-induced lipid accumulation, providing a foundation for the toxicity study and risk assessments of nanoplastics. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Hepatotoxicity; Lipid metabolism; Lipophagy; Nanoplastics; Nanotoxicity |
| المشرفين على المادة: | 0 (Polystyrenes) EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog) EC 2.7.11.31 (AMP-Activated Protein Kinases) EC 2.7.11.1 (ULK1 protein, human) 0 (Microplastics) 0 (Intracellular Signaling Peptides and Proteins) |
| تواريخ الأحداث: | Date Created: 20240619 Date Completed: 20240808 Latest Revision: 20240808 |
| رمز التحديث: | 20240808 |
| DOI: | 10.1016/j.jhazmat.2024.134878 |
| PMID: | 38897115 |
| قاعدة البيانات: | MEDLINE |
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