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. Author manuscript; available in PMC: 2014 Feb 27.
Published in final edited form as: Neurobiol Dis. 2012 Aug 27;0:13–21. doi: 10.1016/j.nbd.2012.08.016

Figure 6.

Figure 6

HIF-PHD inhibitors upregulate p21 and protect cortical neurons from glutathione depletion-mediated cell death. A-H, E14.5 mouse cortical neurons were treated with the concentrations of HIF-PHD inhibitors that were toxic to DLD-1 and N2A in figures 4 and 5: DFO 50 μM, CPO 1 μM, DHB 20 μM, and DMOG 250 μM. A, each compound upregulated p21 mRNA levels, *=P<0.05, one-way ANOVA-Bonferroni’s post test, n=7, B, while all but DMOG upregulated p21 protein levels. C, oxidative stress was induced by glutathione depletion with HCA 5 mM. Co-treatment with DFO, CPO, and DHB completely protected neurons from cell death. *=P<0.001, two-way ANOVA-Bonferroni’s post test, n=4. D-H, fluorescence micrographs of calcein-labeled cortical neurons treated for 3 days with HIF-PHD inhibitors show no basal toxicity. Note the more robust neurite outgrowth in DFO and CPO-treated neurons compared to controls (D-F). Scale bar = 25 μm.