Article: Nrf2 transcriptional derepression from Keap1 by dietary polyphenols
Biochemical and biophysical research communications. 2016 Jan. 15, v. 469
2016
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 ... ...
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. |
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Keywords | RNA ; RNA interference ; antioxidants ; gene expression ; genes ; liver ; neoplasms ; oxidative stress ; polyphenols ; toxins ; transcription (genetics) ; transcription factors ; ubiquitin-protein ligase ; Antioxidant ; Antioxidant response element ; Detoxification ; Dietary polyphenols ; Cytoprotection ; ARE ; hQR1 ; GST-Ya ; Nrf2 ; Keap1 ; t-BHQ ; DMSO |
Language | English |
Dates of publication | 2016-0115 |
Size | p. 521-528. |
Publishing place | Elsevier Inc. |
Document type | Article |
ZDB-ID | 205723-2 |
ISSN | 0006-291X ; 0006-291X |
ISSN (online) | 0006-291X |
ISSN | 0006-291X |
DOI | 10.1016/j.bbrc.2015.11.103 |
Database | NAL-Catalogue (AGRICOLA) |
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