Department of Orthopedics, Xuanwu Hospital, 71044Capital Medical University, Beijing, China.
Cerebrovascular and Neuroscience Research Institute, Beijing Institute of Geriatrics, Xuanwu Hospital, 71044Capital Medical University, Beijing, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221129786. doi: 10.1177/09603271221129786.
Acrylamide (ACR) is a water-soluble chemical applied in industrial and laboratory processes. The neurotoxicity induced by acrylamide involves both peripheral and central nervous system. Hence, there is a growing urgency to investigate the mechanisms of acrylamide-induced neurotoxicity and search novel therapeutic target for the nerve repair. The effects of ACR on the proliferation, reactive oxygen species (ROS) and iron production of dorsal root ganglia (DRG) neurons and Schwann cells were determined. 5-Ethynyl-2-deoxyuridine (EDU) staining and transwell assay were applied to detect the proliferation and migration capacity of DRG cells. Ferrostatin-1 (Fer-1) was used to suppress ferroptosis induced by ACR. RT-PCR analysis was performed to examine the expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and glial cell line-derived neurotrophic factor (GDNF). Moreover, Iron, ROS, malondialdehyde (MDA) and glutathione (GSH) contents were measured to reveal the regulation of ferroptosis in ACR-related nerve injury. ACR inhibited the proliferation and migration of DRG neurons and the supplementation of Fer-1 reversed the effects induced by ACR. Besides, the treatment of Fer-1 effectively increased the expression of NGF, BDNF, VEGF and GDNF. Furthermore, ACR increased the iron level, MDA and ROS contents while inhibited the level of GSH. It was unveiled that ACR attenuated the proliferation, migration and neuron repair of DRG neurons through regulating ferroptosis. The modulation of ferroptosis might be a promising therapeutic strategy and provide references for future treatment of acrylamide-induced nerve damage.
丙烯酰胺（ACR）是一种水溶性化学物质，应用于工业和实验室过程中。丙烯酰胺诱导的神经毒性涉及外周和中枢神经系统。因此，迫切需要研究丙烯酰胺诱导的神经毒性的机制，并寻找神经修复的新治疗靶点。本研究旨在探讨丙烯酰胺对背根神经节（DRG）神经元和雪旺细胞增殖、活性氧（ROS）和铁生成的影响。应用 5-乙炔基-2-脱氧尿苷（EDU）染色和 Transwell 实验检测 DRG 细胞的增殖和迁移能力。使用铁抑素-1（Fer-1）抑制丙烯酰胺诱导的铁死亡。采用 RT-PCR 分析检测神经营养因子脑源性神经营养因子（BDNF）、神经生长因子（NGF）、血管内皮生长因子（VEGF）和胶质细胞源性神经营养因子（GDNF）的表达。此外，测定铁、ROS、丙二醛（MDA）和谷胱甘肽（GSH）含量，揭示 ACR 相关神经损伤中铁死亡的调控。结果显示，丙烯酰胺抑制 DRG 神经元的增殖和迁移，Fer-1 的补充逆转了丙烯酰胺的作用。此外，Fer-1 的处理有效增加了 NGF、BDNF、VEGF 和 GDNF 的表达。进一步研究表明，丙烯酰胺增加铁水平、MDA 和 ROS 含量，同时抑制 GSH 水平。综上，本研究表明，丙烯酰胺通过调节铁死亡抑制 DRG 神经元的增殖、迁移和神经元修复。铁死亡的调节可能是一种有前途的治疗策略，并为未来丙烯酰胺诱导的神经损伤治疗提供参考。
