Consistent with the inhibitory role of KEAP1 in regulating NRF2-ARE activity, KEAP1-KD cells exhibited enhanced expression of the ARE-dependent genes HMOX-1, NQ01, SRX1, GCLC, and GCLM
under basal conditions [Figure 2C, D; see also Supplemental Material, Figure 1C, D http://dx.
As shown in Figure 3, 6-HITC activated Nrf2 and up-regulated downstream proteins associated with the detoxification and excretion of MeHg, such as GCLM
, GCLC, GSTA1, MRP1, and MRP2, in primary mouse hepatocytes.
2010)], HMOX1 (heme oxygenase 1; NM_002133), NQOl (NM_000903), SRX (sulfiredoxin 1; NM_080725), GCLC ([gamma]-glutamate cysteine ligase catalytic subunit; NM_001498), and GCLM ([gamma]-glutamate cysteine ligase regulatory subunit; NM_002061), described in Supplemental Material, Table 1 (doi:10.
Furthermore, the expression of NRF1 downstream targets GCLC and GCLM were attenuated (see Supplemental Material, Figure 3C,D), Indicating that NRF1 activity is suppressed in NRF1-KD cells.