Background: Ischemia/reperfusion (I/R) is a pathological process that causes severe damage. Propofol is known to alleviate I/R-related injury; however, the exact function and underlying mechanisms are not fully understood.
Methods: Using an oxygen glucose deprivation/re-oxygenation (OGD/R) method, an in vitro I/R injury model was induced. The cell viability and the level of Fe2+, glutathione synthetase (GSH), and malondialdehyde (MDA) were evaluated using kits. Luciferase reporter gene assay, chromatin immunoprecipitation, and RNA immunoprecipitation (RIP) were used to verify the interaction between molecules. The m6A level of BECN1 mRNA was determined through methylated RIP.
Results: Propofol-treated OGD/R models showed reduced levels of Fe2+ and MDA, while the cell viability and the level of GSH increased. Propofol inhibited ferroptosis by down-regulating HIF-1α in OGD/R-treated HT22 cells. HIF-1α is bound to the promoter region of YTHDF1 to promote its transcription, and YTHDF1 promoted ferroptosis by stabilizing the mRNA of BECN1. The suppressive effect of propofol on OGD/R-induced ferroptosis was reversed by the overexpression of YTHDF1.
Conclusions: Our study revealed that the HIF-1α/YTHDF1/BECN1 axis in OGD/R-treated HT22 cells promotes ferroptosis, and administration of propofol can inhibit this axis to avoid cell death. This study provides a novel insight for the neuroprotective function of propofol.
Keywords: HIF-1α; Ischemia/reperfusion; ferroptosis; oxygen glucose deprivation/re-oxygenation; propofol.