脊髓损伤
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Figure 5｜Determination of the important progression period of ferroptosis following SCI.
ACSL4, which influences lipid composition, acts as an important component for ferroptosis execution (Doll et al., 2017). ACSL4 has been considered as a ferroptosis related-marker (Yuan et al., 2016). Our analysis of DEGs related to ferroptosis also showed that ACSL4 expression changes after SCI. We measured ACSL4 expression in the spinal cord at various time points after SCI by immunofluorescence staining and found that ACSL4 expression was upregulated at 1 day after SCI compared with 3 and 7 days after injury (Figure 5A and B).
Ferroptosis induced by iron overload is characterized by lipid peroxidation. MDA, the final product of lipid oxidation, inhibits mitochondrial respiratory chain complexes and critical enzyme activities, and it can also exacerbate membrane damage (Ayala et al., 2014; Rui et al., 2020). Therefore, the level of MDA can reflect the degree of lipid peroxidation. We found that the maximal surge in MDA content occurred within 1 day after SCI (Figure 5C).
GSH plays a vital role in the antioxidant protection of cells because of its ability to degrade toxic lipid peroxides to nontoxic fatty alcohols catalyzed by glutathione peroxidase 4 (GPX4) (Ursini and Maiorino, 2020). We found that GSH levels were clearly depleted on the first day after SCI, which indirectly indicates that the progression of ferroptosis may be more severe and drastic at this time point (Figure 5D).