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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Voynow, JA; Fischer, BM; Zheng, S; Potts, EN; Grover, AR; Jaiswal, AK; Ghio, AJ; Foster, WM

Published Date

  • July 2009

Published In

Volume / Issue

  • 41 / 1

Start / End Page

  • 107 - 113

PubMed ID

  • 19059883

Pubmed Central ID

  • 19059883

Electronic International Standard Serial Number (EISSN)

  • 1535-4989

International Standard Serial Number (ISSN)

  • 1044-1549

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2008-0381OC

Language

  • eng