Department of Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning Province, People's Republic of China.
Metallomics. 2017 Aug 16;9(8):1120-1131. doi: 10.1039/c7mt00182g.
Lanthanum (La) exposure can lead to learning and memory disorder in animals; however, the underlying mechanism of La induced neurotoxicity is still unknown. It has been demonstrated that Nrf2 activation by tert-butylhydroquinone (tBHQ) results in neuroprotection against brain injuries. However, little study has been done with respect to its effect on La induced neurotoxicity. Herein, experiments are undertaken to determine if there is a correlation between La damaged astrocytes and the Nrf2/ARE signalling pathway. Primary rat astrocytes are exposed to 0 mmol L, 0.125 mmol L, 0.25 mmol L and 0.5 mmol L lanthanum chloride (LaCl) for 24 hours. The results reveal that LaCl increases the apoptosis/necrosis rate of astrocytes, decreases the glutathione (GSH) content, increases reactive oxygen species (ROS) levels and significantly down-regulates Nrf2 as well as the mRNA and protein expression of Nrf2-regulated genes, including NADP(H): dehydrogenase quinone 1 (NQO1), hemeoxygenase-1 (HO-1), superoxide dismutase 2 (SOD), glutathione peroxidase 1 (GSH-Px), glutathione-s-transferase (GST) and γ-glutamine cysteine synthase (γ-GCS) in astrocytes. In addition, it is found that tBHQ displays an antagonistic effect on astrocytes damaged by LaCl. Therefore, La damaged astrocytes are possibly related to the down-regulated Nrf2/ARE pathway, and treatment with tBHQ clearly activates the Nrf2/ARE signalling pathway, which exerts protection against oxidative stress.
镧（La）暴露会导致动物学习和记忆障碍；然而，镧诱导神经毒性的潜在机制尚不清楚。已证明叔丁基对苯二酚（tBHQ）激活 Nrf2 可导致脑损伤的神经保护。然而，对于其对 La 诱导的神经毒性的影响，研究甚少。在此，进行实验以确定 La 损伤的星形胶质细胞与 Nrf2/ARE 信号通路之间是否存在相关性。将原代大鼠星形胶质细胞暴露于 0mmol/L、0.125mmol/L、0.25mmol/L 和 0.5mmol/L 氯化镧（LaCl）24 小时。结果表明，LaCl 增加星形胶质细胞的凋亡/坏死率，降低谷胱甘肽（GSH）含量，增加活性氧（ROS）水平，并显著下调 Nrf2 以及 Nrf2 调节基因的 mRNA 和蛋白表达，包括 NADP（H）：醌 1 脱氢酶（NQO1）、血红素加氧酶-1（HO-1）、超氧化物歧化酶 2（SOD）、谷胱甘肽过氧化物酶 1（GSH-Px）、谷胱甘肽-s-转移酶（GST）和γ-谷氨酰半胱氨酸合酶（γ-GCS）。此外，发现 tBHQ 对 LaCl 损伤的星形胶质细胞表现出拮抗作用。因此，La 损伤的星形胶质细胞可能与下调的 Nrf2/ARE 途径有关，tBHQ 的治疗明显激活了 Nrf2/ARE 信号通路，对氧化应激发挥保护作用。
