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Am J Respir Cell Mol Biol. 2009 Jul;41(1):107-13. doi: 10.1165/rcmb.2008-0381OC. Epub 2008 Dec 4.

NAD(P)H quinone oxidoreductase 1 is essential for ozone-induced oxidative stress in mice and humans.

Author information

1
Division of Pediatric Pulmonary Medicine, Department of Pediatrics, Duke University Medical Center, Box 2994, Durham, NC 27710, USA. voyno001@mc.duke.edu

Abstract

One host susceptibility factor for ozone identified in epidemiologic studies is NAD(P)H quinone oxidoreductase 1 (NQO1). We hypothesized that after ozone exposure, NQO1 is required to increase 8-isoprostane (also known as F(2)-isoprostane) production, a recognized marker of ozone-induced oxidative stress, and to enhance airway inflammation and hyperresponsiveness. In this report, we demonstrate that in contrast to wild-type mice, NQO1-null mice are resistant to ozone and have blunted responses, including decreased production of F(2)-isoprostane and keratinocyte chemokine, decreased airway inflammation, and diminished airway hyperresponsiveness. Importantly, these results in mice correlate with in vitro findings in humans. In primary human airway epithelial cells, inhibition of NQO1 by dicumarol blocks ozone-induced F(2)-isoprostane production and IL-8 gene expression. Together, these results demonstrate that NQO1 modulates cellular redox status and influences the biologic and physiologic effects of ozone.

PMID:
19059883
PMCID:
PMC2701957
DOI:
10.1165/rcmb.2008-0381OC
[Indexed for MEDLINE]
Free PMC Article
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