contributes to sevoflurane-induced ferroptotic neuronal death in SH-SY5Y cells via the 5' AMP-activated protein kinase/mammalian target of rapamycin pathway.

BACKGROUND

() has been reported to serve as a major player in the progress of ferroptosis in various diseases. Nevertheless, the functional role and mechanism of in sevoflurane (sev)-induced neuronal death has never been elucidated.

METHODS

Cell viability was assessed using Cell Counting Kit-8 (CCK-8). Iron levels, reactive oxygen species (ROS) production, and malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and glutathione (GSH) content were determined to assess ferroptosis level. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot were undertaken for the measurement of gene expression.

RESULTS

Sev hindered the viability of SH-SY5Y cells and suppression of ferroptosis by ferrostatin-1 (Fer-1) mitigated sev-induced inhibition of SH-SY5Y cell viability. Sev treatment increases the Fe level and decreases the mRNA levels of and in SH-SY5Y cells. Sev increased the expression of . Moreover, silencing of could abrogate sev-induced cell damage, as evidenced by increases in cell viability, GPX4 protein levels, and decreases in iron levels, ROS production, and MDA and 4-HNE content. Remarkably, sev hindered the activation of the 5' AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, which was diminished by knockdown of . Moreover, inhibition of the AMPK/mTOR signaling by compound C could mitigate the protective effect of silencing against sev-induced ferroptotic cell death.

CONCLUSIONS

Downregulation of restrained sev-induced ferroptotic cell death via AMPK/mTOR signaling, providing the basis for an approach to alleviate sev-induced postoperative cognitive dysfunction (POCD).