Gastrodin protects against glutamate-induced ferroptosis in HT-22 cells through Nrf2/HO-1 signaling pathway
Gastrodin protects against glutamate-induced ferroptosis in HT-22 cells through Nrf2/HO-1 signaling pathway
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DOI：
10.1016/j.tiv.2019.104715
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发表时间：
2020-02-01
影响因子：
3.2
通讯作者：
Li, Qinglin
中科院分区：
文献类型：
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作者：
Jiang, Ting;Cheng, Hui;Li, Qinglin
天麻素（GAS）是天麻中的一种成分，在神经退行性疾病中具有很强的抗氧化活性。铁凋亡类似于谷氨酸诱导的细胞死亡。本研究旨在探讨天麻素对谷氨酸诱导的小鼠海马神经元（HT-22）细胞毒性的保护作用。HT-22细胞在GAS（1、5、25 μ M）存在或不存在下与谷氨酸一起培养。结果表明GAS通过Nrf 2/HO-1信号通路抑制谷氨酸诱导的铁凋亡。GAS预处理HT-22细胞可显著降低谷氨酸诱导的细胞死亡和LDH释放。铁蛋白抑制素-1，livestatin-1，和DFO治疗取消这些影响。GAS降低谷氨酸处理的HT-22细胞中ROS的产生。金属分析表明，GAS预处理使HT-22细胞中的铁离子浓度归一化。结果发现GAS可增加谷氨酸诱导的HT-22细胞Nrf 2的核转位，上调下游HO-1蛋白的表达。Nrf 2敲低通过HO-1大大降低谷氨酸诱导的铁凋亡。以上结果提示GAS可能通过Nrf 2/HO-1信号通路对谷氨酸诱导的HT-22细胞铁凋亡具有保护作用。
Gastrodin (GAS) is a component of Gastrodia data Blume, with strong antioxidant activity in neurodegenerative diseases. Ferroptosis is similar to glutamate-induced cell death. This study was designed to explore the protective effects of GAS against glutamate-induced neurotoxicity in mice hippocampal neurons (HT-22) cells. HT-22 cells were cultured with glutamate in the presence or absence of GAS (1, 5, 25 mu M). Results showed that GAS inhibited glutamate-induced ferroptosis via Nrf2/HO-1 signaling pathway. Pretreatment of HT-22 cells with GAS significantly decreased glutamate-induced cell death and release of LDH. Ferrostatin-1, liproxstatin-1, and DFO treatments canceled these effect. GAS decreased glutamate-treatment ROS production in HT-22 cells. The concentration of iron ion was analyzed using ICP-MS. Metal analysis showed that GAS pretreatment normalized iron ion concentration in HT-22 cells. We found that GAS increased the nuclear translocation of Nrf2, up-regulated the downstream HO-1 protein expression in HT-22 cells following treatment with glutamate. Nrf2 knockdown greatly decreased glutamate-induced ferroptosis through HO-1. In conclusion, these results show that GAS protects HT-22 cells from the ferroptosis induced by glutamate through a new mechanism of Nrf2/HO-1 signaling pathway.