Nrf2, Transition Metals and Quinones-- Implications for Diseases Involving Metals and Oxygen

To our knowledge, we provide the first experimental evidence that the para- and ortho-hydroquinones themselves are unable to activate Nrf2 directly and that their corresponding quinones react with Keap1 and are the direct activators of Nrf2. In addition, we show that in the presence of Cu2+, the catechol estrogens 2-hydroxyestradiol, 4-hydroxyestradiol, 4-hydroxyestrone, as well as dopamine, are potent Nrf2 activators.

 Further,

"hydroquinones will not stimulate Nrf2-mediated gene induction in the absence of transition metals and oxygen. These findings are of particular importance for certain human conditions in which the levels of transition metals are increased, such as Wilson's disease (genetic mutation in the copper transporter resulting in copper accumulation) or patients with cancer (who have increased plasma and tumor copper levels), and especially in tissues that are exposed to relatively high concentrations of oxygen, such as the lung, the brain, and the alveolar epithelium of the breast."

Wang, X. J., Hayes, J. D., Higgins, L. G., Wolf, C. R., and Dinkova-Kostova, A. T. (2010). Activation of the nrf2 signaling pathway by copper-mediated redox cycling of para- and ortho-hydroquinones. Chemistry & Biology, 17(1). http://www.citeulike.org/user/HEIRS/article/6699335