Journal
TOXICOLOGY IN VITRO
Volume 62, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2019.104715
Keywords
Gastrodin; Glutamate; Ferroptosis; Nrf2/HO-1 pathway; Neurodegenerative diseases
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Funding
- Anhui Provincial Education Department's Outstanding Talents Cultivation project [gxgwfx2019027]
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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.
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