TY - JOUR
T1 - Cobalt nanoparticles induce mitochondrial damage and β-amyloid toxicity via the generation of reactive oxygen species
AU - Chen, Jingrong
AU - Chen, Cheng
AU - Wang, Na
AU - Wang, Chunyu
AU - Gong, Zhaohui
AU - Du, Jingxian
AU - Lai, Honglin
AU - Lin, Xinpei
AU - Wang, Wei
AU - Chang, Xiangyu
AU - Aschner, Michael
AU - Guo, Zhenkun
AU - Wu, Siying
AU - Li, Huangyuan
AU - Zheng, Fuli
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - Aβ toxicity
KW - Caenorhabditis elegans
KW - Cobalt nanoparticles
KW - Drp-1
KW - Mito Q
KW - Reactive oxygen species
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U2 - 10.1016/j.neuro.2023.01.010
DO - 10.1016/j.neuro.2023.01.010
M3 - Article
C2 - 36716931
AN - SCOPUS:85147338755
SN - 0161-813X
VL - 95
SP - 155
EP - 163
JO - Neurotoxicology
JF - Neurotoxicology
ER -