ERK/MAPK Inhibitor PD98059 Induces NMDAR-Mediated Cell Death in SCN2.2 Cells.

A: Live cells in GT1-7 and SCN2.2 cultures exposed to normal culture conditions (control); 10 µM PD98059 (PD); 10 mM Glu (Glu); or 10 mM Glu+10 µM PD98059 (Glu+PD) for 48 h. PD98059 was added 1 h prior to Glu, and continued throughout Glu treatment. Live cells were measured with the Live/Dead assay. Results are mean ± SD from 2 experiments with n = 18 in each. B: Dead cells as measured by Live/Dead assay for same samples as in A. C: % Metabolic activity in GT1-7 and SCN2.2 cultures exposed to normal culture conditions (control); 10 µM PD98059 (PD); 10 µM MK-801 (MK); 10 µM PD98059+10 µM MK-801 (PD+MK); 50 µM NMDA+10 µM MK-801 (NMDA+MK); 50 µM NMDA+10 µM MK-801+10 µM PD98059 (NMDA+MK+PD); 50 µM NMDA (NMDA); or 50 µM NMDA+10 µM PD98059 (NMDA+PD) for 48 h. Inhibitors were added 1 h prior to NMDA. Metabolic activity was measured with the MTS assay. Results are mean ± SD from 2 experiments with n = 12 each. D: % Metabolic activity in GT1-7 and SCN2.2 cultures exposed to normal culture conditions (control); 10 µM PD98059 (PD); 10 µM MK-801 (MK); 10 µM PD98059+10 µM MK-801 (PD+MK); 10 mM Glu+10 µM MK-801 (NMDA+MK); 10 mM Glu+10 µM MK-801+10 µM PD98059 (Glu+MK+PD); 10 mM Glu (Glu); or 10 mM Glu+10 µM PD98059 (NMDA+PD) for 48 h. Inhibitors were added 1 h prior to Glu. Metabolic activity was measured with the MTS assay. Results are mean ± SD from 2 experiments with n = 12 each. All data analyzed by two-way ANOVA with Bonferroni's post hoc test. Comparisons of GT1-7 vs. SCN2.2 within a treatment group are indicated by: * = p<0.05; ** = p<0.01; *** = p<0.001; **** = p<0.0001. Comparisons of treatment groups vs. control within either GT1-7 or SCN2.2 cells are indicated by: b = p<0.01; c = p<0.001; d = p<0.0001.