Figure 10. Quantification of toxicity.
A) Disease-linked mutations in TDP-43 increase caspase 3/7 activity after arsenite treatment. HEK 293 cells were transfected with EGFP, or TDP43 (WT, Q331K or Q343R). After 48 hrs the cells were treated ±50 µM arsenite, 12 hrs later caspase 3/7 activity was assayed under each condition. Results are shown normalized to EGFP transfected cells under basal conditions. B) BE-M17 cells were transfected with EGFP, or TDP43 (WT, G294A or Q331K). LDH release was measured after 48 hrs and normalized to total LDH and transfection efficiency. Baseline toxicity was set as the EGFP transfected neurons. Transfection with TDP-43 (WT, G294A or Q331K) increased LDH release, with G294A and Q331K TDP-43 causing significantly more release than WT TDP-43 (N = 6 measurements per group). C.) Induction of TDP-43 inclusions by arsenite (50 µM) at 12 hrs.
