Induction of γ-globin gene expression by activators of the NRF2 antioxidant response element signaling pathway. (A) The human γ-globin gene promoter contains an ARE consensus sequence. (B) Compounds that activate NRF2/ARE pathway signaling. (C) Effect of NRF2 activators on NQO1 and γ-globin mRNA levels. K562 cells were treated with nontoxic doses of each compound for 12 hours before RNA isolation. (D) Time course of tBHQ, curcumin, and D3T induction of NQO1 and γ-globin mRNA in K562 cells. Real-time PCR was performed in triplicate. Results are presented as relative mRNA expression normalized to untreated (C) or DMSO treated (D) samples. Error bars represent ± SEM, *P < .05, compared with DMSO.