FIGURE 9. Inhibition of Hsp72 in naked mole-rat supernatants [SN_NMR] with a specific small-molecule inhibitor pifithrin-μ attenuates the ability to convey resistance in a dose-dependent manner.

(A) In both reconstituted naked mole-rat samples (Prot + SN; left panel) and human proteasomes [h26S] resuspended in SN_NMR (right panel), and then treated with 20μM MG132, the well-preserved chymotrypsin-like [ChT-L] proteasome activity declined with the addition of increasing concentrations of pifithrin-μ. Significant interference with the inhibition resistance was apparent at the 10μ – 50 μM range of pifithrin-μ concentrations. (B) However, pifithrin-μ did not significantly affect activity of the uninhibited proteasome until much higher concentrations (500 μM). Even then, the activity of pifithrin-μ - treated proteasomes was not lower than activity of the h26S in buffer alone.