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Oxidative Stress and Respiratory Diseases: The Critical Role of Nrf2

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Studies on Respiratory Disorders

Abstract

Molecular oxygen and nitrogen have high affinities for electrons, and the addition of electrons to these molecules can lead to highly reactive compounds, including superoxide (O −2 ), hydrogen peroxide (H2O2), hydroxyl radical (•OH), ozone (O3), nitric oxide (NO), peroxynitrite (ONOO−), and others. These oxidants react with lipids, proteins, and nucleotides to alter the function of these macromolecules and promote cellular injury and death. A high percentage of mammalian genomes are devoted to detoxify this oxidative stress, which is regulated by the transcription factor, Nrf2. Nrf2 serves protective roles in a variety of pulmonary and extra-pulmonary diseases through its transcriptional induction of hundreds of antioxidative and cytoprotective genes, resulting in a coordinated response to environmental stressors. Experiments using animal models and human in vitro or ex vivo cells demonstrate that Nrf2 can protect from a variety of respiratory diseases. These studies are supported by analysis of polymorphisms in patient samples, demonstrating that alterations to the Nrf2 pathway correlate with pathogenic responses. Thus, Nrf2 activators present viable therapeutic options for these and other diseases, and multiple Nrf2 activators are currently being explored in clinical trials.

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Conflict of Interest

Shyam Biswal and the Johns Hopkins University hold intellectual property on the development of Nrf2-based therapeutics for COPD. Cureveda LLC has licensed this intellectual property. Thomas Sussan has no conflict.

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Authors and Affiliations

  1. Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Thomas E. Sussan Ph.D. & Shyam Biswal Ph.D.

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  1. Thomas E. Sussan Ph.D.
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  2. Shyam Biswal Ph.D.
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Correspondence to Shyam Biswal Ph.D. .

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Editors and Affiliations

  1. Department of Biotechnology, National Institute of Immunology, New Delhi, India

    Nirmal K. Ganguly

  2. Department of Pulmonary Medicine, Postgraduate Institute of Medical Educat, Chandigarh, India

    Surinder K. Jindal

  3. Department of Medicine and Oncology, Johns Hopkins College of Medicine, Baltimore, Maryland, USA

    Shyam Biswal

  4. National Heart & Lung Institute, Imperial College London, London, United Kingdom

    Peter J. Barnes

  5. Department of Pediatrics, Nippon Medical School, Tokyo, Japan

    Ruby Pawankar

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Sussan, T.E., Biswal, S. (2014). Oxidative Stress and Respiratory Diseases: The Critical Role of Nrf2. In: Ganguly, N., Jindal, S., Biswal, S., Barnes, P., Pawankar, R. (eds) Studies on Respiratory Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0497-6_17

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