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Alteration of GSSG/GSH Ratio Modulates Expression of Phase 2 Detoxifying Enzymes through Nrf2 Signaling Pathway
Author(s) -
Kim Jong-Sang,
Han Jung-Hwa,
Seo Jiyeon,
Lim Ji Sun,
Jung Chaelim,
Park In-Sil,
Kang Hye-ryung,
Kim Seong Soon,
Kim Hyo Jung,
Yoon Jung Han Park
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.692.3
Subject(s) - glutathione , chemistry , glutathione reductase , biochemistry , sulforaphane , oxidative stress , pentose phosphate pathway , enzyme , glutathione disulfide , nad+ kinase , glutathione peroxidase , glycolysis
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.