Propofol is a short-acting
intravenous anesthetic that is widely used in clinical treatment. Previous articles have indicated that
propofol is a therapeutic target for anti-apoptosis, anti-
inflammation, anti-lipid peroxidation, and anti-
reactive oxygen species (ROS). Moreover, cell ferroptosis is strongly correlated with cellular ROS, inflammatory responses, and lipid peroxidation. However, the mechanisms by which
propofol attenuates neuronal injury by reducing ferroptosis remain unknown. Hence, we hypothesized that
propofol could protect neurons by reducing ferroptosis. To test this hypothesis, HT-22 cells were treated with a specific ferroptosis activator (
erastin) in the presence of
propofol (50 μM). We found that
propofol reduced
erastin-induced high Fe2+ concentrations,
lipid peroxides, and excess ROS. Western blotting results also suggested 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 the Ser663 point is the critical role of
propofol in rescuing
erastin-induced cell injury/lipid peroxidation. In conclusion,
propofol may help attenuate ferroptosis, which may provide a new therapeutic method to treat neuronal injury or the brain inflammatory response.