Alteration of GSSG/GSH Ratio Modulates Expression of Phase 2 Detoxifying Enzymes through Nrf2 Signaling Pathway

Glutathione (GSH), a coenzyme of glutathione peroxidase, is involved in protection of cells from oxidative stress through termination of oxidants with concomitant oxidation of GSH to GSSG. The ratio of GSH/GSSG is viewed as the major indicator of the cellular redox status. We investigated whether intracelluar level of GSH or GSH/GSSG ratio plays an important role in Nrf2‐mediated regulation of phase 2 detoxifying enzymes such as NAD(P)H:quinone oixdoreductase (QR). In order to change the ratio of GSH/GSSG, we attempted to deplete NADPH, a cofactor of glutathione reductase, by inhibiting pentose phosphate pathway in mouse hepatoma cell (Hepa1c1c7) and measured the phase 2 enzyme expression. We also examined whether some known phase 2 enzyme inducers such as tert‐butylhydroquinone (tBHQ), sulforaphane, delphinidin, genistein and glyceollins exert their effect by modulating GSSG/GSH ratio. Our data suggest that perturbation of intracellular GSSG/GSH ratio affects the expression of phase 2 detoxifying and antioxidant enzymes maybe through Nrf2 signaling pathway.