Fig. 5: iPLA2β acts as a major suppressor of p53-mediated ferroptosis.
From: iPLA2β-mediated lipid detoxification controls p53-driven ferroptosis independent of GPX4
a Western blot analysis of extracts of A375 CRISPR control (lanes 1, 2) versus p53 −/− cells (lanes 3, 4) treated with control RNAi (lanes 1, 3) or iPLA2β RNAi (lanes 2, 4) by the antibodies to iPLA2β, p53, p21, or actin. The experiments were repeated twice, independently, with similar results. b Quantification of ROS-induced ferroptotic cell death. The same cells in (a) were pre-incubated with 10 μM Nutlin for 24 h, then treated with 120 μM TBH and 10 μM Nutlin (error bars, s.d. from three independent samples). c Quantification of ferroptotic cell death-mediated by ROS. After iPLA2β RNAi treatment, MCF-7 cells were pre-incubated with 10 μM Nutlin for 24 h, then treated with 80 μM TBH and 10 μM Nutlin (error bars, s.d. from three independent samples). d Western blot analysis of extracts of A375 CRISPR control (lanes 1, 2), p53−/− cells (lanes 3, 4), iPLA2β−/− cells (lanes 5, 6), or p53−/−; iPLA2β−/− cells treated with Nutlin 10 μM for 24 h (lanes 2, 4, 6, 8) versus control (lanes 1,3, 5, 7) by the antibodies to iPLA2β, p53, p21, or actin. The experiments were repeated twice, independently, with similar results. e Quantification of cell death in the same cells as (d) with additional of 150 μm TBH as indicated. Error bars are mean ± s.d., n = 3 biologically independent experiments. f Quantification of ROS-mediated ferroptotic cell death. U2OS CRISPR control versus iPLA2β−/− cells pre-incubated with Nutlin (10 μM) for 24 h were treated with TBH (250 μM), Nutlin (10 μM) and Ferr-1 (2 μM) as indicated (error bars, s.d. from three independent replicates). Source data are provided as a Source Data file.
