Propofol Protects Against Erastin-Induced Ferroptosis in HT-22 Cells

Autor: Wenting Xuan, Xinyi Lu, Zeyong Yang, Jun Li, Weilin Jin, Yuanhai Li
Rok vydání: 2022
Předmět:
Zdroj: Journal of Molecular Neuroscience. 72:1797-1808
ISSN: 1559-1166
0895-8696
Popis: Propofol is a short-acting intravenous anesthetic, which is widely used in clinical treatment. Previous articles indicated that propofol is a therapeutic target for anti-apoptosis, anti-inflammation, anti-lipid peroxidation, and anti-Reactive oxygen species (ROS). Moreover, cell ferroptosis has strong correlations with cellular ROS, inflammatory responses, and lipid peroxidation. However, the mechanisms of propofol attenuating neuron injury by reducing ferroptosis remain unknown. Hence, we hypothesized that propofol could protect neuron cells via reducing cell ferroptosis. To test this hypothesis, HT-22 cells were treated with a specific ferroptosis activator (erastin) in the presence of propofol (50 μM). In such a study, we found propofol reduced erastin induced high Fe 2+ concentration, lipid peroxides, and excess ROS. The western blot also helps us understand that propofol could rescue erastin-induced low expression of GXP4 and system Xc - . Further experiments indicated that propofol attenuated p-ALOX5 expression at Ser663 independent of ERK. In addition, we built two transient transfection cell lines, ALOX5 OE, and Ser663Ala-ALOX5 OE to confirm the target of propofol. We found that Ser663 point is the critical role of propofol in rescuing erastin induced cell injury/lipid peroxidation. In conclusion, propofol may help attenuates ferroptosis, which may provide a new therapeutic method to treat neuron injury or brain inflammatory response.
Databáze: OpenAIRE
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