Nrf2, not the estrogen receptor, mediates catechol estrogen-induced activation of the antioxidant responsive element

Dietary clofibrate inhibits induction of hepatic antioxidant enzymes by chronic estradiol in female ACI rats

“…For example, physiological concentrations of E 2 (10 nM) were found to repress expression of GST-ARE dependent gene expression in vitro, and also decrease uterine expression of this enzyme and NQO1 in female C57Bl/6J mice in vivo (Ansell et al, 2004). In contrast, 4-hydroxyestradiol but not E 2 activated ARE-dependent expression of NQO1 in human neuroblastoma cells and Nrf2 positive primary astrocytes via an estrogen receptor-independent pathway (Lee et al, 2003). Results above indicating that dietary clofibrate completely inhibited the induction of NQO1 and GST in livers of female ACI rats treated chronically with E 2 are noteworthy; and suggest that clofibrate modified signaling pathways connected with the induction of these two enzymes.…”

The role of Nrf2 in increased reactive oxygen species and DNA damage in prostate tumorigenesis

“…Estrogens have been implicated in prostate carcinogenesis by several mechanisms such as upregulation of growth factor signaling pathways, an increased expression of antiapoptotic regulators and increased ROS induced DNA damage (reviewed in Ho et al (2006)). In addition, Lee et al (2003a) has demonstrated that catechol estrogen can induce Nrf2 translocation and activation in neuroblastoma and astrocytes in a PI3K-dependant manner. In normal cells, Nrf2 may induce expression of GSTs, which then conjugates catechol estrogen to glutathione.…”

La Autoantigen Mediates Oxidant Induced De Novo Nrf2 Protein Translation

“…As a bZIP transcription factor, Nrf2 can bind and activate the antioxidant response element (ARE) in the promoters of target genes, including NA-D(P)H:Quinone Oxidoreductase 1, glutathione S-transferases, epoxide hydrolase-1, hemeoxygenase-1, superoxide dismutases, thioredoxin reductase, and peroxiredoxin 1 (1)(2)(3). Whereas Nrf2 controls the antioxidant response, oxidants are a major inducer of Nrf2 protein and activity.…”