Low Doses of Arsenic in a Mouse Model of Human Exposure and in Neuronal Culture Lead to S-Nitrosylation of Synaptic Proteins and Apoptosis via Nitric Oxide
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ijms-21-03948-v2.pdf
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Author(s)
Amal, Haitham
Gong, Guanyu
Yang, Hongmei
Joughin, Brian A.
Wang, Xin
Knutson, Charles G. F.
Kartawy, Maryam
Khaliulin, Igor
Wishnok, John S.
Tannenbaum, Steven R
Date Issued
May 2020
Journal
International Journal of Molecular Sciences
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Amal, Haitham et al. "Low Doses of Arsenic in a Mouse Model of Human Exposure and in Neuronal Culture Lead to S-Nitrosylation of Synaptic Proteins and Apoptosis via Nitric Oxide." International Journal of Molecular Sciences 21, 11 (May 2020): 3948 ©2020 Author(s)
Version
Final published version
Abstract
Background: Accumulating public health and epidemiological literature support the hypothesis that arsenic in drinking water or food affects the brain adversely. Methods: Experiments on the consequences of nitric oxide (NO) formation in neuronal cell culture and mouse brain were conducted to probe the mechanistic pathways of nitrosative damage following arsenic exposure. Results: After exposure of mouse embryonic neuronal cells to low doses of sodium arsenite (SA), we found that Ca[superscript 2+] was released leading to the formation of large amounts of NO and apoptosis. Inhibition of NO synthase prevented neuronal apoptosis. Further, SA led to concerted S-nitrosylation of proteins significantly associated with synaptic vesicle recycling and acetyl-CoA homeostasis. Our findings show that low-dose chronic exposure (0.1-1 ppm) to SA in the drinking water of mice led to S-nitrosylation of proteomic cysteines. Subsequent removal of arsenic from the drinking water reversed the biochemical alterations. Conclusions: This work develops a mechanistic understanding of the role of NO in arsenic-mediated toxicity in the brain, incorporating Ca[superscript 2+] release and S-nitrosylation as important modifiers of neuronal protein function.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.3390/ijms21113948
