Fig. 7: Per2 modulates Gpx4 relies on PPARα in microglia.
a Endogenous protein interactions were assessed in whole cell lysates from microglia by immunoprecipitation with anti-Per2 or anti-IgG, and examined by immunoblotting with anti-PPARα (n = 3 independent experiments) (the repeated immunoblot is shown in Supplementary Fig. 6b, c). b Endogenous protein interactions were confirmed in whole cell lysates from microglia by immunoprecipitation with anti-PPARα or anti-IgG, and examined by immunoblotting with anti-Per2 (n = 3 independent experiments) (the repeated immunoblot is shown in Supplementary Fig. 6d, e). c Per2OE microglia following a 24-h incubation with 10 μM GW6471, a potent PPARα antagonist, to inhibit PPARα expression. The expression of Gpx4 was measured by western blotting. d Quantification of relative levels of Gpx4 protein (n = 3 biological repeats for each group). e The expression of Gpx4 was measured by qRT-PCR (n = 4 biological repeats for each group). f We proposed a model of Per2 regulating the microglial ferroptosis. Lipid peroxidation induces Per2 expression via the MAPK signaling pathway. Per2 subsequently inhibits the expression of Gpx4 by directly interacting with PPARα, which promotes microglia ferroptosis. All data are presented as the mean ± SD. P values were determined by one-way ANOVA with Tukey’s multiple-comparisons test (d, e). *P < 0.05; **P < 0.01; ns not significant.
