help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on December 4, 2008, doi:10.1165/rcmb.2008-0381OC

Am. J. Respir. Cell Mol. Biol., Volume 41, Number 1, July 2009, 107-113

A more recent version of this article appeared on July 1, 2009
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2008-0381OCv1
41/1/107    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Voynow, J. A.
Right arrow Articles by Foster, W. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Voynow, J. A.
Right arrow Articles by Foster, W. M.

Submitted on October 8, 2008
Accepted on December 3, 2008

NAD(P)H Quinone Oxidoreductase 1 Is Essential for Ozone-induced Oxidative Stress in Mice and Humans

Judith A. Voynow1*, Bernard M Fischer1, Shuo Zheng1, Erin Potts2, Amy Grover1, Anil K. Jaiswal3, Andrew J. Ghio4, and W. Michael Foster5

1 Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, United States, 2 Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States, 3 Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland, United States, 4 Human Studies Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, United States, 5 Department of Medicine, Duke Unversity Medical Center, Durham, North Carolina, United States

* To whom correspondence should be addressed. E-mail: voyno001{at}mc.duke.edu.

One host susceptibility factor for ozone identified in epidemiologic studies is NAD(P)H quinone oxidoreductase 1 (NQO1). We hypothesized that following ozone exposure, NQO1 is required to increase 8-isoprostane (also known as F2-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 F2-isoprostane and keratinocyte chemokine, decreased airway inflammation, and diminished airway hyperreponsiveness. 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 F2-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.
Key words: ozone • NAD(P)H quinone oxidoreductase 1 • F2-isoprostane




This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
J. S. Brown
Acute Effects of Exposure to Ozone in Humans: How Low Can Levels Be and Still Produce Effects?
Am. J. Respir. Crit. Care Med., August 1, 2009; 180(3): 200 - 201.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. B. Adler and S. Matalon
Highlights of the July Issue
Am. J. Respir. Cell Mol. Biol., July 1, 2009; 41(1): 1 - 2.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2008 American Thoracic Society. 		  CCM abstracts