Oxidative Stress and Respiratory Diseases: The Critical Role of Nrf2

Chapter
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

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.

Keywords

Chronic Obstructive Pulmonary Disease Acute Lung Injury Chronic Obstructive Pulmonary Disease Patient Idiopathic Pulmonary Fibrosis Chronic Obstructive Pulmonary Disease Exacerbation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Environmental Health SciencesJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA

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