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Nrf2 transcriptional derepression from Keap1 by dietary polyphenols

Bayele, HK; Debnam, ES; Srai, KS; (2016) Nrf2 transcriptional derepression from Keap1 by dietary polyphenols. Biochemical and Biophysical Research Communications , 469 (3) pp. 521-528. 10.1016/j.bbrc.2015.11.103. Green open access

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Abstract

The liver expresses batteries of cytoprotective genes that confer cellular resistance to oxidative stress and xenobiotic toxins, and protection against cancer and other stress-related diseases. These genes are mainly regulated by Nrf2, making this transcription factor a target for small molecule discovery to treat such diseases. In this report, we identified dietary polyphenolic antioxidants that not only activated these genes but also relieved Nrf2 repression by Keap1, a Cul3-dependent ubiquitin ligase adaptor protein that mediates its degradation. Analysis of postprandial liver RNA revealed a marked activation of both genes by all test polyphenols compared with controls. Nrf2 inhibition by RNA interference reduced polyphenol effects on its target gene expression. Our data suggest that polyphenols may induce cellular defense genes by derepressing Nrf2 inhibition by Keap1. We posit that this ability to derepress Nrf2 and reactivate its target genes may underlie the protection conferred by polyphenols against oxidative stress-related diseases.

Type: Article
Title: Nrf2 transcriptional derepression from Keap1 by dietary polyphenols
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bbrc.2015.11.103
Publisher version: http://dx.doi.org/10.1016/j.bbrc.2015.11.103
Language: English
Additional information: © 2015. This manuscript version is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International licence (CC BY-NC-ND 4.0). This licence allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licences are available at http://creativecommons.org/licenses/by/4.0.
Keywords: Antioxidant, Antioxidant response element, Detoxification, Dietary polyphenols, Cytoprotection
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1473276
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