Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress
| Autor: | B. Kevin Park, Ian M. Copple, Fiona E. Mutter |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Macromolecular Substances
NF-E2-Related Factor 2 Context (language use) Oxidative phosphorylation Pharmacology Biology medicine.disease_cause Biochemistry S2 The Keap1/Nrf2 Pathway in Health and Disease hazard assessment antioxidant response element nuclear factor erythroid 2-related factor 2 (Nrf2) medicine Humans Kelch-like ECH-associated protein 1 (Keap1) Transcription factor Regulation of gene expression chemistry.chemical_classification Reactive oxygen species toxicity stress response Cell biology Oxidative Stress chemistry Gene Expression Regulation Toxicity Signal transduction Reactive Oxygen Species Biochemical Society Focused Meetings Oxidative stress Signal Transduction |
| Zdroj: | Biochemical Society Transactions |
| ISSN: | 1470-8752 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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