Arsenic affects expression and processing of amyloid precursor protein (APP) in primary neuronal cells overexpressing the Swedish mutation of human APP

• DOI: 10.1016/j.ijdevneu.2011.03.004
• Publication Date: 2011-03-31T05:28:34Z
• Authors: Sergio Zarazúa; Susanne Bürger; Juan M. Delgado; Maria E. Jiménez‐...; Reinhard Schliebs
• Keywords: Sodium arsenite; Neurotoxicity; Amyloid (mycology)

Abstract Arsenic poisoning due to contaminated water and soil, mining waste, glass manufacture, select agrochemicals, as well sea food, affects millions of people world wide. Recently, an involvement arsenic in Alzheimer's disease (AD) has been hypothesized (Gong O'Bryant, 2010). The present study stresses the hypothesis whether sodium arsenite, its main metabolite, dimethylarsinic acid (DMA), may affect expression processing amyloid precursor protein (APP), using cholinergic cell line SN56.B5.G4 primary neuronal cells overexpressing Swedish mutation APP, experimental approaches. Exposure with either arsenite or DMA decreased viability a concentration‐ exposure‐time dependent manner, affected activities enzymes acetylcholinesterase choline acetyltransferase. Both exposure resulted enhanced level sAPP membrane cytosolic fractions, respectively. To reveal any effect on APP processing, amounts cleavage products, sAPPβ, β‐amyloid (Aβ) peptides, released into culture medium derived from transgenic Tg2576 mice, were assessed by ELISA. Following for 12 h, membrane‐bound was enhanced, amount sAPPβ slightly higher, while levels Aβ peptides considerably lower compared that assayed absence drug. arsenite‐induced reduction formation suggests inhibition γ‐cleavage step arsenite. In contrast, increased accompanied level. DMA‐induced changes be result expression. Alternatively, production also stimulation caspase activity compounds, failure degradation. summary, report clearly demonstrates vitro.