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. 2013 Jul 3;14(5):645–659. doi: 10.1007/s10162-013-0404-1

FIG. 5.

FIG. 5

Inhibition of the p53 antagonist mdm2 facilitates gentamicin-induced hair cell death. A The Mdm2 inhibitor nutlin-3a sensitizes hair cells to damage caused by a 6-h continuous gentamicin exposure (one-way ANOVA, F(2, 29) = 12.90, P < 0.001), but not to damage from acute neomycin or gentamicin treatment (one-way ANOVAs, neomycin: F(2, 28) = 2.71, P = 0.08; gentamicin: F(2, 32) = 3.03, P = 0.06). Nutlin-3a alone was not toxic to hair cells during the 7-h treatment period (one-way ANOVA, F(2, 30) = 0.49, P = 0.61). B Nutlin-3a attenuates the protection provided by PFTα. Fish were cotreated with nutlin-3a and 25 μM gentamicin with or without PFTα. Hair cell survival was greater in all PFTα groups relative to those without PFTα (two-way ANOVA, F(1, 50) = 105.8, P < 0.001), but survival decreased with increasing concentrations of nutlin-3a in the presence of PFTα (one-way ANOVA, F(2, 23) = 4.81, P = 0.02). Asterisks indicate significant differences between treatment pairs with vs. without PFTα (***P < 0.001). N = 5–11 animals per treatment, data are presented as mean ± 1 SD.