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Figure 7 | Molecular Medicine

Figure 7

From: Pharmacological Rescue of the Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Detected by Use of a Novel Fluorescence Platform

Figure 7

Quantification of corrector efficacy by flow cytometry and short circuit current measurements. Corrector efficacies of single-corrector compounds or combinations, determined by flow cytometry or Ussing chamber measurements are shown. (A) A representative flow cytometry histogram for HEK293 cell lines showing the distribution of MG-11p fluorescence signal for the vehicle control (dashed line) and CFFT-002 + C18 (solid line) corrector treatment. Fluorescence activity is plotted along the horizontal axis using a logarithmic scale. Bar graphs show the mean fluorescence intensity of HEK293 cells expressing either FAP-F508del-CFTR (B) or F508del-CFTR EL4-FAP (C) for each condition, normalized to the effect of C18. Data are presented as the mean ± SEM (n = 3). (D) Short circuit currents were measured across polarized HBE cells, which express endogenous, untagged F508del-CFTR. Corrector efficacy was determined from the currents generated by addition of forskolin and potentiator P2, as described in Research Design and Methods and normalized to the current obtained for C18-treated epithelia (9.0 ± 1.1 ΔIsc (µA/cm2)). Data are presented as the mean ± SEM (n = 6 and n = 36 total observations). (E) Representative traces of short-circuit current (Isc) across primary cultures of HBE cells mounted in Ussing chambers. Isc was measured after treatment of HBE cells with the corrector combination, C18 + CFFT-002, or vehicle (DMSO) for 24 h. Statistical significance is represented as follows: *P = 0.01–0.05; **P = 0.001–0.01, ***P = 0.0001–0.001, ****P — 0.0001.

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