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

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 hippocampa...

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Bibliographic Details
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
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Summary: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. [Display omitted] •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.
ISSN:0887-2333
1879-3177
DOI:10.1016/j.tiv.2019.104715