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Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress
Beyond specific limits of exposure, chemical entities can provoke deleterious effects in mammalian cells via direct interaction with critical macromolecules or by stimulating the accumulation of reactive oxygen species (ROS). In particular, these chemical and oxidative stresses can underpin adverse...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613517/ https://www.ncbi.nlm.nih.gov/pubmed/26551708 http://dx.doi.org/10.1042/BST20150044 |
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author | Mutter, Fiona E. Park, B. Kevin Copple, Ian M. |
author_facet | Mutter, Fiona E. Park, B. Kevin Copple, Ian M. |
author_sort | Mutter, Fiona E. |
collection | PubMed |
description | Beyond specific limits of exposure, chemical entities can provoke deleterious effects in mammalian cells via direct interaction with critical macromolecules or by stimulating the accumulation of reactive oxygen species (ROS). In particular, these chemical and oxidative stresses can underpin adverse reactions to therapeutic drugs, which pose an unnecessary burden in the clinic and pharmaceutical industry. Novel pre-clinical testing strategies are required to identify, at an earlier stage in the development pathway, chemicals and drugs that are likely to provoke toxicity in humans. Mammalian cells can adapt to chemical and oxidative stress via the action of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which up-regulates the expression of numerous cell defence genes and has been shown to protect against a variety of chemical toxicities. Here, we provide a brief overview of the Nrf2 pathway and summarize novel experimental models that can be used to monitor changes in Nrf2 pathway activity and thus understand the functional consequences of such perturbations in the context of chemical and drug toxicity. We also provide an outlook on the potential value of monitoring Nrf2 activity for improving the pre-clinical identification of chemicals and drugs with toxic liability in humans. |
format | Online Article Text |
id | pubmed-4613517 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-46135172015-10-23 Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress Mutter, Fiona E. Park, B. Kevin Copple, Ian M. Biochem Soc Trans Biochemical Society Focused Meetings Beyond specific limits of exposure, chemical entities can provoke deleterious effects in mammalian cells via direct interaction with critical macromolecules or by stimulating the accumulation of reactive oxygen species (ROS). In particular, these chemical and oxidative stresses can underpin adverse reactions to therapeutic drugs, which pose an unnecessary burden in the clinic and pharmaceutical industry. Novel pre-clinical testing strategies are required to identify, at an earlier stage in the development pathway, chemicals and drugs that are likely to provoke toxicity in humans. Mammalian cells can adapt to chemical and oxidative stress via the action of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which up-regulates the expression of numerous cell defence genes and has been shown to protect against a variety of chemical toxicities. Here, we provide a brief overview of the Nrf2 pathway and summarize novel experimental models that can be used to monitor changes in Nrf2 pathway activity and thus understand the functional consequences of such perturbations in the context of chemical and drug toxicity. We also provide an outlook on the potential value of monitoring Nrf2 activity for improving the pre-clinical identification of chemicals and drugs with toxic liability in humans. Portland Press Ltd. 2015-08-03 2015-08-01 /pmc/articles/PMC4613517/ /pubmed/26551708 http://dx.doi.org/10.1042/BST20150044 Text en © 2015 Authors; published by Portland Press Limited |
spellingShingle | Biochemical Society Focused Meetings Mutter, Fiona E. Park, B. Kevin Copple, Ian M. Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress |
title | Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress |
title_full | Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress |
title_fullStr | Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress |
title_full_unstemmed | Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress |
title_short | Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress |
title_sort | value of monitoring nrf2 activity for the detection of chemical and oxidative stress |
topic | Biochemical Society Focused Meetings |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613517/ https://www.ncbi.nlm.nih.gov/pubmed/26551708 http://dx.doi.org/10.1042/BST20150044 |
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