Gastrodin protects against glutamate-induced ferroptosis in HT-22 cells through Nrf2/HO-1 signaling pathway

• Published in: Toxicology in vitro Vol. 62; p. 104715
• Main Authors: Jiang, Ting, Cheng, Hui, Su, Jingjing, Wang, Xuncui, Wang, Qiaoxue, Chu, Jun, Li, Qinglin
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-02-2020; Elsevier Science Ltd
• Subjects: Antioxidants; Apoptosis; Cell death; Ferroptosis; Gastrodin; Glutamate; Heme oxygenase (decyclizing); Hippocampus; Ion concentration; Iron; Neurodegenerative diseases; Neurotoxicity; Nrf2/HO-1 pathway; Nuclear transport; Pretreatment; Signal transduction; Signaling; Translocation; Ferroptosis; HO-1; MDA; DFO; MTT; PTGS2; GPX; DMEM; LDH; SD; min; Nrf2; FBS; Gastrodin; Wnt; GSH; GPX4; Neurodegenerative diseases; Fig; h; DAPI; SOD; ACSL4; EDTA; Glutamate; s; Nrf2/HO-1 pathway; ROS; ICP-MS
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2019.104715

Gastrodin (GAS) is a component of Gastrodia elata 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 μM). 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.
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•Glutamate induced ferroptosis through Nrf2/HO-1 signaling pathway.•Gastrodin protects against glutamate-induced ferroptosis in the HT-22 cells.•Gastrodin mediates ferroptosis via Nrf2/HO-1 signaling pathway.