Skip to main content
Advertisement

< Back to Article

Experimental and Computational Analysis of Polyglutamine-Mediated Cytotoxicity

Figure 7

Simulated effects of p38MAPK activation without ROS generation.

A) When the feedback loop is broken by eliminating ROS production the model predicts that cell death will be reduced under all conditions. B) Under ROS-free conditions the model predicts no significant difference in the numbers of inclusions at each time point between untreated polyglutamine-expressing cells or cells treated with a p38MAPK inhibitor. Similarly, no significant difference is predicted in the number of inclusions at early time points between untreated cells or cells treated with a proteasome inhibitor. At later time points (> = 42h) more inclusions are predicted for the PI treated cells due to the accumulation of misfolded protein which cannot be degraded. C) Model re-fitted to data of untreated poly-glutamine-expressing cells predicts more cell deaths but still no significant differences between treatments. D) Model re-fitted to data of untreated poly-glutamine-expressing cells shows no significant differences between untreated and treated cells at early time points. At 48h, the model predicts a small but significant increase in the number of inclusions for cells treated with p38MAPK inhibitor indicating that the model no longer fits the data. The error bars represent the standard error of the percentage given by where n is the number of simulation runs (n = 300) and p is the percentage of cells.

Figure 7

doi: https://doi.org/10.1371/journal.pcbi.1000944.g007