1. דף הבית

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.

Citation:

Haitham Amal, Gong, Guanyu , Yang, Hongmei , Joughin, Brian A, Wang, Xin , Knutson, Charles G, Kartawy, Maryam , Khaliulin, Igor , Wishnok, John S, ו Tannenbaum, Steven R. 2020. “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. doi:10.3390/ijms21113948.

תקציר:

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(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(2+) release and S-nitrosylation as important modifiers of neuronal protein function.