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. 2015 Sep 14;125(10):3819–3830. doi: 10.1172/JCI79048

Figure 4. Drug screening identifies perhexiline as an activator of KLF14.

Figure 4

(A) Diagram of the chemical structure of the perhexiline maleate salt. (B and C) Luciferase activity of reporters was analyzed in HepG2 cells transfected with pGL4-KLF-luc or pGL4–ApoA-I–Luc constructs after 12 hours treatment with 10 μM perhexiline or DMSO. **P < 0.01, Student’s t test. Values represent mean ± SEM; n = 3. (D) HepG2 cells were infected with AdshLacZ or AdshKLF14 for 48 hours and then incubated with 10 μM perhexiline for 24 hours in DMEM containing 0.2% BSA. The ApoA-I concentrations in the medium were detected by ELISA. *P < 0.05, 2-way ANOVA and multiple comparisons. Values represent mean ± SEM; n = 6. (E) HepG2 cells were treated with DMSO or perhexiline at 10 μM for indicated time points in DMEM containing 0.2% BSA, and ApoA-I production was detected by Western blot. (F) HepG2 cells were treated with DMSO or perhexiline at indicated dosage for 24 hours in DMEM containing 0.2% BSA, and ApoA-I production was detected by Western blot. (G) HepG2 cells were treated with DMSO, perhexiline, RVX-208, or etomoxir at 10 μM for 24 hours in DMEM containing 0.2% BSA, and ApoA-I production was detected by Western blot. Quantifications from 3 independent experiments are shown in E–G, and values represent mean ± SEM. *P < 0.05; **P < 0.01, 2-way ANOVA and multiple comparisons.