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. Author manuscript; available in PMC: 2013 Sep 1.
Published in final edited form as: Biochimie. 2012 May 29;94(9):1974–1981. doi: 10.1016/j.biochi.2012.05.020

Figure 4. Treatment with 4-aminoquinoline probes results in a caspase-dependent reduction in TDP-43 levels and increase in CTFs in human H4 cells.

Figure 4

(A) 4-aminoquinolines reduce TDP-43 levels in H4 cells with SAR similar to binding and stimulation of caspase-7 cleavage of TDP-43. H4 cells were plated onto 24-well plates the day before and then treated with test compound for 24 hrs, followed by lysis in SDS sample buffer and immunoblotting (section 2.3). (B) 4-aminoquinoline 1 and 2 reduce full length TDP-43 and increase TDP-43 CTFs in the triton X100 insoluble fraction, and to a lesser extent in the soluble fraction. H4 cells were plated in 6 well plates and treated with test compound as before and subject to fractionation of triton X100 soluble and insoluble fractions as described in section 2.5. (C) The effects of 1 on TDP-43 levels are attenuated by the caspase inhibitors Q-VD-OPh and Ac-DEVD-CHO. H4 cells were plated in 24-well plates and treated with 1 in the presence and absence of 10 μM Q-VD-OPh or Ac-DEVD-CHO for 24 hrs, followed by immunoblotting as before. Blots are examples of single experiments that were replicated with similar results.