Fig. 3: ApoE inhibition of ferroptosis is mediated by suppressing iron release from ferritin.

A ApoE rescue of a lethal dose of erastin is not prevented by co-incubation with five different endocytosis inhibitors, shown (n = 4; MBCD = methyl-beta-cyclodextrin). B Total glutathione (GSH) was measured in N27 neurons at different time intervals following treatment with erastin (0.5 µM) in the presence of either apoE or LPX (n = 6). C Iron levels were measured in N27 neurons after exposure to erastin (0.5 µM, 16 h) in the presence of either apoE or LPX (n = 6). ApoE rescue of a lethal dose of erastin was abolished after incubation with iron (100 µM) (D, E) (n = 3), but preserved when iron was pre-loaded in ferritin prior to erastin exposure (F, G) (n = 5). H, I ApoE rescue of erastin toxicity diminishes over time, compared to LPX, measured by the MTT viability assay at 24 h (H) and 48 h (I) (n = 9). Data are means ± SEM and experiments were repeated at least 3 times. ApoE and LPX were both 200 nM. P values were calculated using one-way ANOVA test corrected for multiple comparison using the Tukey test (A) and Dunnett test (B). ***p < 0.001.