Abstract
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.
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Abbreviations
- 4-HNE:
-
4-Hydroxy-2E-nonenal
- CCK:
-
Cell counting kit
- COX:
-
Cyclooxygenases
- DHE:
-
Dihydroethidium
- Era:
-
Erastin
- EM:
-
Electronic microscopy
- ERK:
-
Extracellular regulated protein kinases
- Fer-1:
-
Ferrostain-1
- GPX4:
-
Glutathione peroxidase 4
- IF:
-
Immunofluorescences
- MK2:
-
MAPK-activated protein kinase 2;
- PPF:
-
Propofol
- PKA:
-
Protein kinase A
- qRT-PCR:
-
Quantitative real-time PCR
- PI:
-
Propidium iodide
- PTGS2:
-
Prostaglandin-endoperoxide synthase 2
- RSL:
-
RAS selective lethal
- ROS:
-
Reactive oxygen species
- mtROS:
-
Mitochondrial ROS
- xCT:
-
System Xc−
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Over the course of my researching and writing this paper, I would like to express my thanks to all those who have helped me.
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YL received Anhui Province Research and Development Program (No. 17041f0804021).
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WX and ZY designed and performed the experiments. XL analyzed the data. XL participated in manuscript writing/editing. LY and WJ contributed significantly to the experimental design and funds.
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Wenting Xuan, Xinyi Lu, and Zeyong Yang contributed equally to this study.
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Xuan, W., Lu, X., Yang, Z. et al. Propofol Protects Against Erastin-Induced Ferroptosis in HT-22 Cells. J Mol Neurosci 72, 1797–1808 (2022). https://doi.org/10.1007/s12031-022-02017-7
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DOI: https://doi.org/10.1007/s12031-022-02017-7