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. 2022 Aug 8;2022:4776243. doi: 10.1155/2022/4776243

Figure 8.

Figure 8

Melatonin upregulates the expression of NRF2 and enhanced NRF2 binding to the Slc7a11 promoter to inhibit ferroptosis. (a) KEGG pathway classification and enrichment of differentially expressed genes in the HR versus NC groups; HR-induced cell death included apoptosis, necroptosis, autophagy, and ferroptosis. (b) The results of the KEGG pathway enrichment analysis of differentially expressed genes (DEGs) showed that glutathione metabolism and ferroptosis (red arrow), more than apoptosis, autophagy, and necroptosis, were among the highly enriched pathways in the HR+MT versus HR groups. (c) Heat map of the KEGG pathway clustering of genes of the ferroptosis pathway in the NC, HR, and HR+MT groups; the expression of Slc7a11 was significantly increased after HR treatment and was remarkably restored by MT therapy. (d, e) MTEC were incubated with or without melatonin for 24 h. Western blotting and immunofluorescence (confocal laser scanning microscope) showing that melatonin promoted NRF2 nuclear translocation. Scale bar = 20 μm. (f, g) ChIP assays and ChIP-qPCR analysis of NRF2 binding to Slc7a11 in MTEC treated with or without melatonin. Data represent the mean ± SEM of 3–4 independent experiments. ∗p < 0.05,  ∗∗p < 0.01, and∗∗∗p < 0.001, compared with the NC group.