Neuroprotection of p53 against glutamate oxidative damage by inhibiting ferroptosis
10.3969/j.issn.1001-1978.2019.05.014
- Author:
Wen-Ting XUAN
1
Author Information
1. Dept of Anesthesiology, First Affiliated Hospital, Anhui Medical University
- Publication Type:Journal Article
- Keywords:
Ferroptosis;
Glutamate-induced injury;
Neurodegenerative disease;
Neuron;
Neuroprotection;
P53
- From:
Chinese Pharmacological Bulletin
2019;35(5):654-660
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the mechanism of the inhibitory effect of apoptosis inducible factor p53 on the toxicity of glutamate in HT22 cell lines. Methods CCK-8 and PI/Hoechst fluorescence double staining were used to detect the survival rate of HT22 cells. Western blot was applied to determine the protein expression levels of p53 and xCT. DHE fluorescence staining technique was employed to detect the intracellular reactive oxygen species ( ROS), and BODIPY 581/591 Cll lipid peroxidation sensor was utilized to confirm intracellular lipid oxidant situation. FeRhoN-ox M-l fluorescent probe was used to assess intracellular ferrous ions. Results After 6 h treatment of 1 μmol • L-1 Tenovin-1, the protein expression levels of p53 obviously increased. After high expression of p53, treatment with Glu and erastin(ferroptosis inducer) for 8 h ( Glu-p53 , Era-p53 groups) , cell death rate decreased significantly, and the expression levels of xCT increased significantly, compared with only Glu and erastin treated groups ( Glu, Era groups ) . Intracelluar ROS levels, lipid oxidant situations, ferrous ions declined in Glu-p53 groups compared to those of Glu group. Conclusions p53 inhibits the neurotoxicity induced by Glu, which may be related to the inhibition of ferroptosis by regulating xCT expression.
