NADPH: Quinone oxidoreductase 1 regulates host susceptibility to ozone via isoprostane generation

Abstract

Background: NQO1 regulates pulmonary susceptibility to ozone. Results: In NQO1-null mice, ozone exposure generates precursors of A2-isoprostane in the lung. A2-isoprostane suppresses ozone-induced IL-8 expression, inhibits NF-KB, and modifies Cys179 in IKK. Conclusion: A2-isoprostane inhibits ozone-induced NF-KB activation via IKK inhibition. Significance: This molecular mechanism explains the paradoxical observation that loss of NQO1 protects from ozone toxicity.© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.