Figure 8

Activation of MST1 in scrapie-infected mice at late stages of disease. Targeted tertiary analyses of MST1 signaling in brainstem-cerebellum, subcortical region, and cortical region of scrapie-infected mice at 70, 90, 110, 130 dpi or at terminal stage of disease (TER; 155–190 dpi). (A) Levels of phosphorylated JNK (T183/Y185), MST1 (T183), FOXO3 (S208), and cleaved MST1, in the brainstem-cerebellums of each of the three scrapie-infected mice at each time point, normalized to those in the mock-infected mice, shown by color bars. The proteins in dashed lines were not analyzed. (B) Phosphorylation levels in all brains regions, normalized to those in the mock-infected mice, shown as time series. Mean ± SD; n = 3 (Mean ± range for MST1 (T183) at 110 dpi [subcortical region] and TER [brainstem-cerebellum], and FOXO3 (S208) at 130 dpi [brainstem-cerebellum] and TER [cortical region]; n = 2). Error bars on the x-axes, range in time of onset of terminal disease. The differences in the phosphorylation levels, or levels of cleaved MST1, in scrapie- versus mock-infected mice were analyzed by two-tailed paired ratio t-test. *(^#, cleaved MST1), P < 0.05.