Cited by 740Genomics, phytochemicals, and oxidative stressNF-κB Signaling PathwaysRedox biology and oxidative stress

Activation of Nrf2-antioxidant signaling attenuates NFκB-inflammatory response and elicits apoptosis

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Li, Wenge, Khor, Tin Oo, Xu, Changjiang, Shen, Guoxiang, Jeong, Woo-Sik, Yu, Siwang, Kong, Ah-Ng·2008·Biochemical Pharmacology

Abstract

Oxidative stress has been implicated in the etiology of neurodegenerative disease, cancer and aging. Indeed, accumulation of reactive oxygen and nitrogen species generated by inflammatory cells that created oxidative stress is thought to be one of the major factor by which chronic inflammation contributes to neoplastic transformation as well as many other diseases. We have recently reported that mice lacking nuclear factor-erythroid 2-related factor 2 (Nrf2) are more susceptible to dextran sulfate sodium (DSS)-induced colitis and colorectal carcinogenesis. Nrf2 is a basic leucine zipper redox-sensitive transcriptional factor that plays a center role in ARE (antioxidant response element)-mediated induction of phase II detoxifying and antioxidant enzymes. We found that increased susceptibility of Nrf2 deficient mice to DSS-induced colitis and colorectal cancer was associated with decreased expression of antioxidant/phase II detoxifying enzymes in parallel with upregulation of pro-inflammatory cytokines/biomarkers. These findings suggest that Nrf2 may play an important role in defense against oxidative stress possibly by activation of cellular antioxidant machinery as well as suppression of pro-inflammatory signaling pathways. In addition, in vivo and in vitro data generated from our laboratory suggest that many dietary compounds can differentially regulate Nrf2-mediated antioxidant/anti-inflammatory signaling pathways as the first line defense or induce apoptosis once the cells have been damaged. In this review, we will summarize our thoughts on the potential cross-talks between Nrf2 and NFkappaB pathways. Although the mechanisms involved in the cross-talk between these signaling pathways are still illusive, targeting Nrf2-antioxidative stress signaling is an ideal strategy to prevent or treat oxidative stress-related diseases.

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Crossref · 10.1016/j.bcp.2008.07.017

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  • The anti-inflammatory role of Nrf2 includes Nrf2-mediated inhibition of the pro-inflammatory NF-κB pathway and inhibition of expression of pro-inflammatory cytokines.

    “The anti-inflammatory role of Nrf2 also includes Nrf2-mediated inhibition of the pro-inflammatory NF-ΚB pathway and inhibition of expression of pro-inflammatory cytokines [195,196,197].”

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Authors
Li, W., Khor, T. O., Xu, C., Shen, G., Jeong, W.-S., Yu, S., & Kong, A.-N.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
Kong, Ah-Ng
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2008-12
Volume
76
Issue
11
Pages
1485-1489
ISSN
0006-2952 (ISSN-L)
OpenAlex
W2064452102
Cited by
738
References
25
Citations by year
2026: 17 · 2025: 32 · 2024: 28 · 2023: 43 · 2022: 66 · 2021: 59 · 2020: 52 · 2019: 58 · 2018: 58 · 2017: 43 · 2016: 52 · 2015: 52 · 2014: 29 · 2013: 48 · 2012: 33
FWCI
9.32
Type
journal article
Language
en
Open access
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R01CA118947, CA094828, R01CA073674, CA-118947, CA073674, R01CA094828)
  • National Institute of Environmental Health Sciences (P30ES005022)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
Nrf2, NF-κB, oxidative stress, antioxidant response element, phase II enzymes, colitis, colorectal cancer, inflammatory cytokines, apoptosis, dietary compounds, chronic inflammation, neurodegenerative diseases, aging
MeSH terms
Animals, Antioxidants, Signal Transduction, NF-kappa B, Apoptosis, Oxidative Stress, Inflammation Mediators, NF-E2-Related Factor 2, Mice

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