Figure 4. Cysteine 151 of KEAP1 is required for NRF2 activation by indomethacin.
(A) Gdf15 mRNA levels in BMDM generated from C151S KEAP1 transgenic animals and littermate controls 6 hours after stimulation with indomethacin or ketoprofen (n=4 per group). (B) NRF2 target gene expression in BMDM generated from C151S KEAP1 transgenic animals and littermate controls 6 hours after stimulation with indomethacin (n=4 per group). (C) Baseline GDF15 serum levels in C151S KEAP1 mice and controls (n=5–7 per group). (D) Plasma GDF15 levels after an intraperitoneal injection of 15 mg/kg indomethacin at the indicated time points in C151S and wildtype animals (n=5–7 per group). (E) mRNA expression of Gdf15, Hmox1, and Nqo1 at 6 hours from bulk liver of C151S and wildtype animals after treatment with 15 mg/kg indomethacin (n=4 per group). All experiments are representative and repeated at least once. Statistics by ANOVA. Data are represented as mean ± standard deviation. **P<0.01, ***P<.001, ****P<.0001