Acrylamide (ACR) is a known neurotoxicant and developmental neurotoxicant. As a soft electrophile, ACR reacts with thiol groups in cysteine. One hypothesis of ACR induced neurotoxicity and developmental neurotoxicity (DNT) is conjugation with reduced glutathione (GSH) leading to GSH depletion, increased reactive oxygen species (ROS) production and further oxidative stress and cellular damage. In this regard, we have investigated the effect of ACR on neuronal differentiation, glutathione levels and ROS production in the human neuroblastoma SH-SY5Y cell model. After 9 days of differentiation and exposure, ACR significantly impaired area neurites per cell at non-cytotoxic concentrations (0.33 μM and 10 μM). Furthermore, 10 μM ACR dysregulated 9 mRNA markers important for neuronal development, 5 of them being associated with cytoskeleton organization and axonal guidance. At the non-cytotoxic concentrations that significantly attenuate neuronal differentiation, ACR did neither decrease the level of GSH or total glutathione levels, nor increased ROS production. In addition, the expression of 5 mRNA markers for cellular stress was assessed with no significant altered regulation after ACR exposure up to 320 μM. Thus, ACR-induced DNT is not due to GSH depletion and increased ROS production, neither at non-cytotoxic nor cytotoxic concentrations, in the SH-SH5Y model during differentiation.

中文翻译：

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丙烯酰胺引起的神经元分化减弱与分化的人神经母细胞瘤 SH-SY5Y 细胞中的氧化应激无关

丙烯酰胺（ACR）是一种已知的神经毒剂和发育神经毒剂。作为一种软亲电子试剂，ACR 与半胱氨酸中的硫醇基团发生反应。 ACR 诱导神经毒性和发育神经毒性 (DNT) 的一种假设是与还原型谷胱甘肽 (GSH) 结合，导致 GSH 消耗、活性氧 (ROS) 产生增加以及进一步的氧化应激和细胞损伤。在这方面，我们研究了ACR对人神经母细胞瘤SH-SY5Y细胞模型中神经元分化、谷胱甘肽水平和ROS产生的影响。分化和暴露 9 天后，ACR 在非细胞毒性浓度（0.33 μM 和 10 μM）下显着损害每个细胞的神经突面积。此外，10 μM ACR 失调了 9 个对神经元发育很重要的 mRNA 标记，其中 5 个与细胞骨架组织和轴突引导相关。在显着减弱神经元分化的非细胞毒性浓度下，ACR 既不会降低 GSH 水平或总谷胱甘肽水平，也不会增加 ROS 产生。此外，在 ACR 暴露至 320 μM 后，评估了 5 种细胞应激 mRNA 标记物的表达，调节没有显着改变。因此，在 SH-SH5Y 模型分化过程中，无论是在非细胞毒性浓度还是细胞毒性浓度下，ACR 诱导的 DNT 都不是由于 GSH 消耗和 ROS 产生增加所致。