2. Academic Validation
  3. Cobalt Nanoparticles Induce Mitochondrial Damage and β-amyloid Toxicity via the Generation of Reactive Oxygen Species

Cobalt Nanoparticles Induce Mitochondrial Damage and β-amyloid Toxicity via the Generation of Reactive Oxygen Species

  • Neurotoxicology. 2023 Jan 27;S0161-813X(23)00018-9. doi: 10.1016/j.neuro.2023.01.010.
Jingrong Chen 1,  Cheng Chen 2,  Na Wang 1,  Chunyu Wang 1,  Zhaohui Gong 1,  Jingxian Du 1,  Honglin Lai 1,  Xinpei Lin 2,  Wei Wang 2,  Xiangyu Chang 2,  Michael Aschner 3,  Zhenkun Guo 4,  Siying Wu 5,  Huangyuan Li 6,  Fuli Zheng 7
Affiliations

Affiliations

  • 1 Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China.
  • 2 Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China; Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China; The key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China.
  • 3 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer 209, 1300 Morris Park Avenue, Bronx, NY 10461.
  • 4 The key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer 209, 1300 Morris Park Avenue, Bronx, NY 10461.
  • 5 Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China; The key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China; Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China.
  • 6 Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China; Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China; The key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China. Electronic address: lhy@fjmu.edu.cn.
  • 7 Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China; Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China; The key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China. Electronic address: f.zheng@fjmu.edu.cn.
PMID: 36716931 DOI: 10.1016/j.neuro.2023.01.010
Abstract

Exposure to cobalt nanoparticles (CoNPs) has been associated with neurodegenerative disorders, while the mitochondrial-associated mechanisms that mediate their neurotoxicity have yet to be fully characterized. In this study, we reported that CoNPs exposure reduced the survival and lifespan in the nematodes, Caenorhabditis elegans (C. elegans). Moreover, exposure to CoNPs aggravated the induction of paralysis and the aggregation of β-amyloid (Aβ). These effects were accompanied by Reactive Oxygen Species (ROS) overproduction, ATP reduction as well as mitochondrial fragmentation. Dynamin-related protein 1 (drp-1) activation and ensuing mitochondrial fragmentation have been shown to be associated with CoNPs-reduced survival. In order to address the role of mitochondrial damage and ROS production in CoNPs-induced Aβ toxicity, the mitochondrial Reactive Oxygen Species scavenger mitoquinone (Mito Q) was used. Our results showed that Mito Q pretreatment alleviated CoNPs-induced ROS generation, rescuing mitochondrial dysfunction, thereby lessening the CoNPs-induced Aβ toxicity. Taken together, we show for the first time, that increasing of ROS and the upregulation of drp-1 lead to CoNPs-induced Aβ toxicity. Our novel findings provide in vivo evidence for the mechanisms of environmental toxicant-induced Aβ toxicity, and can afford new modalities for the prevention and treatment of CoNPs-induced neurodegeneration.

Keywords

Aβ toxicity; Caenorhabditis elegans; Drp-1; Mito Q; cobalt nanoparticles; reactive oxygen species.

Figures
Products