Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Chem Biol. 2010 Jan 29;17(1):75-85. doi: 10.1016/j.chembiol.2009.12.013.

Activation of the NRF2 signaling pathway by copper-mediated redox cycling of para- and ortho-hydroquinones.

Author information

  • 1Cancer Research UK Molecular Pharmacology Unit, Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.

Abstract

Transcription factor NF-E2 p45-related factor 2 (Nrf2) mediates adaptation to oxidants and electrophiles through up-regulating genes that contain antioxidant response elements (AREs) in their promoters. Using the stably transfected human AREc32 reporter cell line, we found that copper and other transition metals enhanced induction of ARE-driven luciferase by 2-tert-butyl-1,4-hydroquinone (tBHQ) as a result of increased oxidation to 2-tert-butyl-1,4-benzoquinone (tBQ). Following exposure to tBHQ for 30 min, ARE-luciferase activity measured after 24 hr was dependent on the presence of Cu(2+). In contrast, tBQ-induced activity was Cu(2+)-independent. The metal-catalyzed oxidation of tBHQ to tBQ occured rapidly and stoichiometrically. Compounds that share para- or ortho-hydroquinone structures, such as catechol estrogens, dopamine, and l-DOPA, also induced ARE-driven luciferase in a Cu(2+)-dependent manner. Thus, the oxidation of para- and ortho-hydroquinones to quinones represents the rate-limiting step in the activation of Nrf2.

Copyright (c) 2010 Elsevier Ltd. All rights reserved.

PMID:
20142043
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk