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Fig. 1
Screening for modifiers of aminoglycoside toxicity.
(A) Neuromast from a control animal pretreated with 0.5% DMSO and stained with rapidly with FM 1-43FX (red) and the nuclear label Yo-Pro-1 (green). (B) Negative control pretreated with 0.05% DMSO for 1 hour followed by 200 μM neomycin treatment for 30 min. Hair cells are stained with FM 1-43FX (red) and Yo-Pro-1 (green). Hair cell loss, nuclear condensation and cytoplasmic shrinking are observed. (C) Dose-response function showing decreased hair cell labeling with DASPEI, a mitochondrial potentiometric dye, as a function of increasing neomycin concentration for wildtype zebrafish (N = 25–37 total fish per group, from triplicate experiments). Bars are SEM. Screens for increased or decreased susceptibility to hair cell loss were performed by treatment with either low, 25 μM, or high, 200 μM, neomycin doses, respectively, as highlighted by the orange arrows. (D) Neuromast pretreated with PROTO-2, a compound identified to provide protection against 200 µM neomycin exposure. (E,F) Show the structure for the identified compounds, PROTO-1 (E) and PROTO-2 (F), respectively.