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NOX2 activation contributes to cobalt nanoparticles-induced inflammatory responses and Tau phosphorylation in mice and microglia
Ecotoxicology and Environmental Safety ( IF 6.2 ) Pub Date : 2021-09-04 , DOI: 10.1016/j.ecoenv.2021.112725
Jing Li 1 , Junxiang Wang 1 , Yuan-Liang Wang 1 , Zhousong Luo 1 , Chunyan Zheng 1 , Guangxia Yu 1 , Siying Wu 2 , Fuli Zheng 1 , Huangyuan Li 3
Affiliation  

Despite the wide application of cobalt nanoparticles (CoNPs), its neurotoxicity and the underlying mechanisms are not fully understood. In this study, CoNPs-induced toxic effect was examined in both C57BL/6J mice and microglial BV2 cells. CoNPs-induced brain weight loss and the reduction of Nissl bodies, assuring neural damage. Moreover, both total unphosphorylated Tau and phosphorylated Tau (pTau; T231 and S262) expressions in the hippocampus and cortex were upregulated, unveiling Tau phosphorylation. Besides, the increase in inflammation-related proteins NLRP3 and IL-1β were found in mice brain. Corroborating that, microglial marker Iba-1 expression was also increased, suggesting microglia-involved inflammation. Among the NADPH oxidase (NOX) family proteins tested, only NOX2 was activated by CoNPs in hippocampus. Therefore, BV2 cells were employed to further investigate the role of NOX2. In BV2 cells, NOX2 expression was upregulated, corresponding to the production of ROS. Moreover, similar induction in Tau phosphorylation and inflammation-related protein expressions were observed in CoNPs-exposed BV2 cells. Treatment of apocynin, a NOX2 inhibitor, reduced ROS generation and reversed Tau phosphorylation and inflammation caused by CoNPs. Thus, CoNPs induced ROS production, Tau phosphorylation and inflammation specially via NOX2 activation.



中文翻译:

NOX2 激活有助于钴纳米颗粒诱导的小鼠和小胶质细胞炎症反应和 Tau 磷酸化

尽管钴纳米粒子 (CoNPs) 应用广泛,但其神经毒性和潜在机制尚不完全清楚。在这项研究中,在 C57BL/6J 小鼠和小胶质细胞 BV2 细胞中检查了 CoNPs 诱导的毒性作用。CoNPs 诱导的脑重量减轻和尼氏体的减少,确保神经损伤。此外,海马和皮层中的总未磷酸化 Tau 和磷酸化 Tau(pTau;T231 和 S262)表达均上调,揭示了 Tau 磷酸化。此外,在小鼠大脑中发现炎症相关蛋白 NLRP3 和 IL-1β 增加。证实了这一点,小胶质细胞标记物 Iba-1 表达也增加,表明小胶质细胞涉及炎症。在测试的 NADPH 氧化酶 (NOX) 家族蛋白中,只有 NOX2 被海马中的 CoNPs 激活。所以,BV2 细胞被用来进一步研究 NOX2 的作用。在 BV2 细胞中,NOX2 表达上调,对应于 ROS 的产生。此外,在暴露于 CoNPs 的 BV2 细胞中观察到类似的 Tau 磷酸化诱导和炎症相关蛋白表达。夹竹桃麻素是一种 NOX2 抑制剂,可减少 ROS 的产生并逆转 CoNP 引起的 Tau 磷酸化和炎症。因此,CoNPs 特别诱导 ROS 产生、Tau 磷酸化和炎症 减少 ROS 的产生并逆转由 CoNPs 引起的 Tau 磷酸化和炎症。因此,CoNPs 特别诱导 ROS 产生、Tau 磷酸化和炎症 减少 ROS 的产生并逆转由 CoNPs 引起的 Tau 磷酸化和炎症。因此,CoNPs 特别诱导 ROS 产生、Tau 磷酸化和炎症通过NOX2 激活。

更新日期:2021-09-04
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