The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress

Nguyen, Truyen; Nioi, Paul; Pickett, Cecil B.

doi:10.1074/jbc.r900010200

Cited by 2,655Genomics, phytochemicals, and oxidative stressRedox biology and oxidative stressGlutathione Transferases and Polymorphisms

The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress

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Nguyen, Truyen, Nioi, Paul, Pickett, Cecil B.·2009·Journal of Biological Chemistry

DOI 10.1074/jbc.r900010200PMC PMC2679427

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Abstract

A major mechanism in the cellular defense against oxidative or electrophilic stress is activation of the Nrf2-antioxidant response element signaling pathway, which controls the expression of genes whose protein products are involved in the detoxication and elimination of reactive oxidants and electrophilic agents through conjugative reactions and by enhancing cellular antioxidant capacity. At the molecular level, however, the regulatory mechanisms involved in mediating Nrf2 activation are not fully understood. It is well established that Nrf2 activity is controlled, in part, by the cytosolic protein Keap1, but the nature of this pathway and the mechanisms by which Keap1 acts to repress Nrf2 activity remain to be fully characterized and are the topics of discussion in this minireview. In addition, a possible role of the Nrf2-antioxidant response element transcriptional pathway in neuroprotection will also be discussed.

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NRF2 coordinates the antioxidative stress response by inducing the expression of cytoprotective mechanisms including heme oxygenase-1 and ferritin.
“NRF2 coordinates the antioxidative stress response as it induces the expression of several cytoprotective mechanisms including heme oxygenase-1 (HO1) and FT (Nguyen et al., 2009).”
From Iron in infection and immunity (2020) · cites this paper as Nguyen et al., 2009
The ARE-mediated Pathway and Nrf2 Activity and Repression by Keap1 sections say that Nrf2 regulates the expression of cytoprotective genes in response to stress. The passages identify GSTA2 and NQO1 as examples, but the copy does not identify heme oxygenase-1 or ferritin as Nrf2-induced genes (searched: heme oxygenase, ferritin, FT). Page numbers are unavailable in the indexed copy. (LLM, conf=0.85)
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Among the eight genes whose perturbation shifted PD-L1 protein levels, five were positive regulators (PD-L1 downregulation upon perturbation) and three were negative regulators.
“We identified five positive regulators (PD-L1 downregulation upon perturbation) and three negative regulators, a subset of which had been previously validated [9,11,13,16,17,29].”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [29]
The citation is attached to the statement that some regulators had been previously validated, not to the citing authors’ count of five positive and three negative regulators. The Nrf2-Keap1 Regulatory Pathway and Molecular Mechanisms Controlling Nrf2 Stabilization sections discuss Nrf2 regulation, but the passages found when searching for PD-L1 and immune-checkpoint regulation do not address PD-L1 or validate its regulators. (LLM, conf=0.76)
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Authors: Nguyen, T., Nioi, P., & Pickett, C. B.
Affiliations: Biogen (United States) (US)
Corresponding author: Pickett, Cecil B.
ORCID: Nioi, Paul
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2009-05
Volume: 284
Issue: 20
Pages: 13291-13295
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.r900010200
PMC: PMC2679427
OpenAlex: W2015392958
Cited by: 2,655
References: 51
Citations by year: 2026: 91 · 2025: 112 · 2024: 169 · 2023: 156 · 2022: 202 · 2021: 218 · 2020: 224 · 2019: 245 · 2018: 212 · 2017: 208 · 2016: 152 · 2015: 121 · 2014: 126 · 2013: 120 · 2012: 87
FWCI: 7.15
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 4253 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords: Nrf2, antioxidant response element, oxidative stress, Keap1, electrophilic stress, detoxification, reactive oxygen species, phase II metabolism, antioxidant capacity, transcriptional regulation, neuroprotection
MeSH terms: Kelch-Like ECH-Associated Protein 1, Animals, Antioxidants, Cytoskeletal Proteins, Gene Expression Regulation, Humans, Transcription, Genetic, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, Response Elements, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, NF-E2-Related Factor 2, Mice

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The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress

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