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.
Int J Mol Sci
; 21(11)2020 May 31.
Article
en En
| MEDLINE
| ID: mdl-32486366
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 Ca2+ 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 Ca2+ release and S-nitrosylation as important modifiers of neuronal protein function.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Arsénico
/
Apoptosis
/
Neuronas
/
Óxido Nítrico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
Israel