Figure 5.

Increasing Hsp70 levels enhances Hsp70 inhibitor efficacy. A, HeLa tau transfectants were cotransfected with vector or myc-tagged Hsp70 and cells were treated with the indicated dose of MB or AC for 1 h. Consistent with a critical role for Hsp70, its overexpression dramatically improved the efficacy of MB and AC. Note that overexpression of Hsp70 alone had only mild effects on tau levels in the absence of inhibitors. Results are shown as a percentage of vehicle control after actin normalization compiled from replicate experiments. B, Quantitation of both AC and MB from experiments in A shows overexpression of Hsp70 significantly increased Hsp70 inhibitor efficacy. Hsp70 overexpression alone did not significantly reduce tau levels. *p < 0.05, **p < 0.01. C, HeLa tau transfectants were treated with 3 μm celastrol (Cel) for 24 h and then treated with indicated concentration of MB for 1 h. Western analysis and quantitation shows that celastrol alone has minor effects on tau levels, whereas celastrol plus MB has much more potent effects than MB alone. Tau levels are represented as a percentage of actin by densitometry.