Nrf2 promotes survival following exposure to ionizing radiation

Sekhar, Konjeti R.; Freeman, Michael L.

doi:10.1016/j.freeradbiomed.2015.04.035

Cited by 110Genomics, phytochemicals, and oxidative stressEffects of Radiation ExposureRedox biology and oxidative stress

Nrf2 promotes survival following exposure to ionizing radiation

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Sekhar, Konjeti R., Freeman, Michael L.·2015·Free Radical Biology and Medicine

DOI 10.1016/j.freeradbiomed.2015.04.035PMC PMC4628893

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Abstract

Nrf2 is a transcription factor that promotes antioxidant and drug-metabolizing gene expression. It also regulates the transcription of genes involved in carbohydrate and lipid metabolism, NADPH regeneration, and heme and iron metabolism, as well as proteasome metabolism. Emerging research has identified Nrf2 as a critical factor for promoting survival of mammalian cells subjected to ionizing radiation. At a mechanistic level, Nrf2 promotes the repair of DNA damage and drives detoxification of superoxide that is generated hours to days after irradiation. This review summarizes research in these areas and discusses targeting of Nrf2 in radiation-resistant cancer and Nrf2׳s role in mitigating acute radiation syndrome.

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Nrf2 plays a key role in cellular defense against oxidative and xenobiotic stressors by inducing expression of genes encoding detoxifying enzymes and antioxidant proteins that provide protection in endothelial cells, skin morphogenesis, wound repair, and skin cancer.
“Nrf2 plays a key role in the cellular defense against oxidative and xenobiotic stressors by its capacity to induce the expression of numerous genes, which encode detoxifying enzymes and antioxidant proteins that provide protection in endothelial cells, skin morphogenesis, wound repair, and skin cancer [70][71][72][73].”
From Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation (2018) · cites this paper as [72]
Nrf2 activation guards against dermal damage from sunlight (ionizing radiation) and oxidative stress via ROS.
“where Nrf2 activation guards against dermal damage, from sunlight (ionizing radiation) and oxidative stress via ROS [2,69-73,76,99].”
From Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation (2018) · cites this paper as [72]
Equol can increase levels of the master gene Nrf2, which regulates endogenous expression of detoxifying proteins and many other antioxidant enzymes involved in wound repair and protection against skin cancer.
“equol itself is a very strong antioxidant, and, in turn, it can increase the levels of the master gene, Nrf2, which regulates the endogenous expression of detoxifying proteins and many other antioxidant enzymes that are involved in wound repair, protection against skin cancer”
From Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation (2018) · cites this paper as [72]

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Effects of Linear Energy Transfer on the Radiolysis of Water and Heavy Water
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A Salidroside‐Based Radiosensitizer Regulates the Nrf2/ROS Pathway for X‐Ray Activated Synergistic Cancer Precise Therapy
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A mitohormetic response to pro-oxidant exposure in the house mouse.
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Nrf2 alleviates radiation-induced rectal injury by inhibiting of necroptosis
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Metformin increases the radiosensitivity of non-small cell lung cancer cells by destabilizing NRF2
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Polysaccharides extracted fromRheum tanguticumameliorate radiation-induced enteritis via activation of Nrf2/HO-1
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DNMT3A R882H mutation drives daunorubicin resistance in acute myeloid leukemia via regulating NRF2/NQO1 pathway
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Autophagy gene Atg7 regulates the development of radiation‐induced skin injury and fibrosis of skin
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Crosstalk between NRF2 and Dicer through metastasis regulating MicroRNAs; mir-34a, mir-200 family and mir-103/107 family
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Methylene Blue Induces Antioxidant Defense and Reparation of Mitochondrial DNA in a Nrf2-Dependent Manner during Cisplatin-Induced Renal Toxicity
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NRF2 Mediates Therapeutic Resistance to Chemoradiation in Colorectal Cancer through a Metabolic Switch
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Vam3 ameliorates total body irradiation-induced hematopoietic system injury partly by regulating the expression of Nrf2-targeted genes
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Dose-Dependent Increase of Nrf2 Target Gene Expression in Mice Exposed to Ionizing Radiation
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Mesenchymal Stem Cells Early Response to Low-Dose Ionizing Radiation
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Adaptation to Chronic-Cycling Hypoxia Renders Cancer Cells Resistant to MTH1-Inhibitor Treatment Which Can Be Counteracted by Glutathione Depletion
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Catalase Modulates the Radio-Sensitization of Pancreatic Cancer Cells by Pharmacological Ascorbate
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Jdp2 is a spatiotemporal transcriptional activator of the AhR via the Nrf2 gene battery
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NRF2-driven redox metabolism takes center stage in cancer metabolism from an outside-in perspective
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Authors: Sekhar, K. R., & Freeman, M. L.
Affiliations: Vanderbilt University (US)
Corresponding author: Freeman, Michael L.
ORCID: Sekhar, Konjeti R.
Freeman, Michael L.
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2015-11
Volume: 88
Issue: Pt B
Pages: 268-274
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/j.freeradbiomed.2015.04.035
PMC: PMC4628893
OpenAlex: W767415338
Cited by: 109
References: 91
Citations by year: 2026: 5 · 2025: 14 · 2024: 9 · 2023: 12 · 2022: 6 · 2021: 15 · 2020: 16 · 2019: 3 · 2018: 10 · 2017: 12 · 2016: 4 · 2015: 3
FWCI: 0.94
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Free Radical Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: NIH/NHLBI (RO1HL112286)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: Nrf2, ionizing radiation, radioresistance (biology), DNA repair, superoxide detoxification, antioxidant gene expression, radiation sickness, cell survival
MeSH terms: Animals, Cell Survival, DNA Repair, Humans, Radiation Tolerance, Radiation, Ionizing, NF-E2-Related Factor 2

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Nrf2 promotes survival following exposure to ionizing radiation

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