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- _5 value "Nrf1 and Nrf2 Regulate a Similar Subset of Antioxidant Genes: Expression of Gclm was reduced to the same extent in both Nrf1 and Nrf2 mutant cells. NQO1 was down-regulated to a similar extent in both single mutant cells, whereas mRNA levels of heme-oxygenase-1 (HO-1), ferritin-H (FtH), and metallothionein-1 (MT-1) was lower in nrf2–/– cells compared with nrf1–/– cells (Fig. 6a). In all cases, however, expression in double knockout cells was abolished compared with single knockout cells, indicating a dependence on both Nrf1 and Nrf2" provenance.