Nrf2 promotes survival following exposure to ionizing radiation

Sekhar, Konjeti R.; Freeman, Michael L.

doi:10.1016/j.freeradbiomed.2015.04.035

Cited by 88 publications

(71 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent studies have demonstrated that NRF2 promotes DNA repair and drives detoxification of superoxide that is generated after irradiation (137). In particular, NRF2 regulates the expression of RAD51, many DNA repair genes, including those of homologous recombination repair pathway, and have putative antioxidant response elements (68).…”

Section: Ionizing and Uv-radiationmentioning

confidence: 99%

Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective

Ghezzi

Floridi

Boraschi

et al. 2018

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

Section: Ionizing and Uv-radiationmentioning

confidence: 99%

Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective

Ghezzi

Floridi

Boraschi

et al. 2018

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

“…Under basal/low-stress conditions, Nrf2 is sequestered in the cytoplasm by kelch-like ECH-associated protein 1 (Keap1), an adaptor for a Cul3-based E3 ligase that promotes constitutive proteasome-mediated Nrf2 degradation (35, 36). Keap1, however, by virtue of its numerous oxidizable cysteine residues (27 in human), is capable of responding to diverse forms of oxidative stress to generate a common output, namely the activation of Nrf2 (37). This involves an increase in the levels of the Nrf2 protein and its translocation from the cytoplasm to the nucleus where it binds to antioxidant response elements (AREs) located within gene promoters.…”

Section: Nrf2 Involvement In the Early Antioxidant Responsementioning

confidence: 99%

Defenses against Pro-oxidant Forces - Maintenance of Cellular and Genomic Integrity and Longevity

2018

View full text Add to dashboard Cite

There has been enormous recent progress in understanding how human cells respond to oxidative stress, such as that caused by exposure to ionizing radiation. We have witnessed a significant deciphering of the events that underlie how antioxidant responses counter pro-oxidant damage to key biological targets in all cellular compartments, including the genome and mitochondria. These cytoprotective responses include: 1. The basal cellular repertoire of antioxidant capabilities and its supporting cast of facilitator enzymes; and 2. The inducible phase of the antioxidant response, notably that mediated by the Nrf2 transcription factor. There has also been frenetic progress in defining how reactive electrophilic species swamp existing protective mechanisms to augment DNA damage, events that are embodied in the cellular “DNA-damage response”, including cell cycle checkpoint activation and DNA repair, which occur on a time scale of hours to days, as well as the implementation of cellular responses such as apoptosis, autophagy, senescence and reprograming that extend the time period of damage sensing and response into weeks, months and years. It has become apparent that, in addition to the initial oxidative insult, cells typically undergo further waves of secondary reactive oxygen/nitrogen species generation, DNA damage and signaling and that these may reemerge long after the initial events have subsided, probably being driven, at least in part, by persisting DNA damage. These reactive oxygen/nitrogen species are an integral part of the pathological consequences of radiation exposure and may persist across multiple cell divisions. Because of the pervasive nature of oxidative stress, a cell will manifest different responses in different subcellular compartments and to different levels of stress injury. Aspects of these compartmentalized responses can involve the same proteins (such as ATM, p53 and p21) but in different functional guises, e.g., in cytoplasmic versus nuclear responses or in early-versus late-phase events. Many of these responses involve gene activation and new protein synthesis as well as a plethora of post-translational modifications of both basal and induced response proteins. It is these responses that we focus on in this review.

show abstract

“…In the setting of radiation, NADPH oxidase activity is increased in lung tissue 6 , which is known to enhance, and in some settings be required for, Nrf2 expression 31, 32 , presumably reducing lung injury. Studies in Nrf2 deficient mice have demonstrated a substantial increase in late lung injury after localized irradiation 33, 34 . This injury is associated with an enhanced level of isoleuvoglandin (IsoLG) modification of proteins, an event that can alter protein function 35 .…”

Section: Oxidative Stressmentioning

confidence: 99%

Mechanisms of Normal Tissue Injury From Irradiation

Citrin

Mitchell

2017

Seminars in Radiation Oncology

View full text Add to dashboard Cite

Normal tissue injury from irradiation is an unfortunate consequence of radiotherapy. Technologic improvements have reduced the risk of normal tissue injury, however toxicity causing treatment breaks or long term side effects continue to occur in a subset of patients. The molecular events that lead to normal tissue injury are complex and span a variety of biologic processes, including oxidative stress, inflammation, depletion of injured cells, senescence, and elaboration of pro-inflammatory and pro-fibrogenic cytokines. This manuscript describes selected recent advances in normal tissue radiobiology.

show abstract

Nrf2 promotes survival following exposure to ionizing radiation

Cited by 88 publications

References 85 publications

Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective

Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective

Defenses against Pro-oxidant Forces - Maintenance of Cellular and Genomic Integrity and Longevity

Mechanisms of Normal Tissue Injury From Irradiation

Contact Info

Product

Resources

About