Apoptosis Inducible Factor P53 Decrease Glutamate-Associated Damage via Inhibiting Ferroptosis

BACKGROUND: Ferroptosis, a pattern of programmed cell death decided by iron-associated lipid peroxidation, however, its role of p53-mediated xCT pathway in HT22 cell death remains obscure. Herein, this study is to investigate the potential mechanism of the effect of p53-mediated xCT pathway in HT22 cell lines in an iron-relevant mode. METHODS: The viability of HT22 cells were detected by Cell Counting Kit-8(CCK-8) and PI/Hoechst fluorescence double staining. The protein expression levels of p53 and xCT were determined by western boltting. DHE fluorescence staining technique supervised the intracellular reactive oxygen species (ROS), and intracellular lipid oxidant situation was confirmed by BODIPY 581/591 C11 lipid peroxidation sensor. Intracellular ferrous ions were monitored with FeRhoNox™-1 fluoresceent probe. RESULTS: The protein expression levels of p53 was obviously enhanced by tenovin-1 exposure. Accompanied with the upregulation of p53 protein, cell death was decreased significantly because of glutamate and erastin exposure with 8h, and p53-mediated xCT pathway was activated. Intracelluar ROS levels, lipid oxidant situations and ferrous ions were remarkably restricted from Glutamate-p53 groups in comparison with glutamate groups. CONCLUSIONS: Overall, P53-mediated xCT pathway could decrease the glutamate-associated neurotoxicity, which may be relevant to the inhibition of ferroptosis.