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首页> 外文期刊>Archives of Toxicology >Diazinon oxon affects the differentiation of mouse N2a neuroblastoma cells
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Diazinon oxon affects the differentiation of mouse N2a neuroblastoma cells

机译：Diazinon oxon影响小鼠N2a神经母细胞瘤细胞的分化

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摘要

The aim of this study was to assess the neurotoxicity of diazinon oxon (DZO), a major in vivo metabolite of the phosphorothionate insecticide diazinon (DZ), on differentiating mouse N2a neuroblastoma cells. When used at concentrations of 1, 5 and 10 μM, DZO did not cause cell death but it impaired the outgrowth of axon-like processes after 24 h. Densitometric scanning of Western blots of lysates of N2a cells revealed that exposure to 5 or 10 μM DZO for 24 h increased the expression of phosphorylated neurofilament heavy chain (NFH) compared to controls, while there was no significant change in total NFH. By contrast, treatment of N2a cells with 1–10 μM DZO resulted in marked reductions in the expression of the axon growth-associated protein GAP-43. DZO-treated cells also showed an increased expression of the heat shock protein HSP-70 compared to controls. The above biochemical changes were not temporally related to inhibition of acetylcholinesterase (AChE). These data suggest that biologically relevant, subcytotoxic levels of DZO may exert neurotoxic effects on differentiating cells and that the mechanisms involved are different from those attributed to its parent compound.
机译：这项研究的目的是评估对硫磷杀虫剂二嗪农（DZ）的主要体内代谢产物二嗪农牛（DZO）对分化的小鼠N2a神经母细胞瘤细胞的神经毒性。当以1、5和10μM的浓度使用时，DZO不会引起细胞死亡，但会在24小时后损害轴突样过程的生长。 N2a细胞裂解物的蛋白质印迹的光密度扫描显示，与对照组相比，暴露于5或10μMDZO 24小时可增加磷酸化神经丝重链（NFH）的表达，而总NFH则无明显变化。相比之下，用1-10μMDZO处理N2a细胞会导致轴突生长相关蛋白GAP-43的表达明显降低。与对照相比，DZO处理的细胞还显示出热激蛋白HSP-70的表达增加。上述生化变化在时间上与抑制乙酰胆碱酯酶（AChE）无关。这些数据表明，DZO的生物学相关性，亚细胞毒性水平可能会对分化细胞产生神经毒性作用，并且所涉及的机制与归因于其母体化合物的机制不同。

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