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

  • Toxicol In Vitro. 2020 Feb;62:104715. doi: 10.1016/j.tiv.2019.104715.
Ting Jiang  1 ,  Hui Cheng  2 ,  Jingjing Su  2 ,  Xuncui Wang  2 ,  Qiaoxue Wang  2 ,  Jun Chu  3 ,  Qinglin Li  4
Affiliations
  • 1. Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, People's Republic of China; School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China.
  • 2. Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, People's Republic of China.
  • 3. Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, People's Republic of China. Electronic address: [email protected].
  • 4. Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, People's Republic of China. Electronic address: [email protected].
PMID: 31698019 DOI: 10.1016/j.tiv.2019.104715
Abstract

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.

Keywords
Ferroptosis; Gastrodin; Glutamate; Neurodegenerative diseases; Nrf2/HO-1 pathway.
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