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NADPH:Quinone Oxidoreductase 1 Regulates Host Susceptibility to Ozone via Isoprostane Generation

Overview of attention for article published in Journal of Biological Chemistry, December 2012
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Title
NADPH:Quinone Oxidoreductase 1 Regulates Host Susceptibility to Ozone via Isoprostane Generation
Published in
Journal of Biological Chemistry, December 2012
DOI 10.1074/jbc.m112.438440
Pubmed ID
Authors

Apparao B. Kummarapurugu, Bernard M. Fischer, Shuo Zheng, Ginger L. Milne, Andrew J. Ghio, Erin N. Potts-Kant, W. Michael Foster, Erik J. Soderblom, Laura G. Dubois, M. Arthur Moseley, J. Will Thompson, Judith A. Voynow

Abstract

NADPH:quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1 as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. However, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1 ozone exposure results in increased generation of A(2)-isoprostane, a cyclopentenone isoprostane that blunts inflammation. Using GC-MS, we found that NQO1-null mice had greater lung tissue levels of D(2)- and E(2)-isoprostanes, the precursors of J(2)- and A(2)-isoprostanes, both at base line and following ozone exposure compared with congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells that A(2)-isoprostane inhibited ozone-induced NF-κB activation and IL-8 regulation. Furthermore, we determined that A(2)-isoprostane covalently modified the active Cys(179) domain in inhibitory κB kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A(2)-isoprostane inhibition of NF-κB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A(2)-isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 18%
Researcher 3 18%
Professor > Associate Professor 2 12%
Professor 2 12%
Student > Master 1 6%
Other 2 12%
Unknown 4 24%
Readers by discipline Count As %
Medicine and Dentistry 5 29%
Biochemistry, Genetics and Molecular Biology 3 18%
Pharmacology, Toxicology and Pharmaceutical Science 2 12%
Agricultural and Biological Sciences 1 6%
Computer Science 1 6%
Other 2 12%
Unknown 3 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 January 2013.
All research outputs
#10,958,570
of 12,366,242 outputs
Outputs from Journal of Biological Chemistry
#51,140
of 53,824 outputs
Outputs of similar age
#226,456
of 269,138 outputs
Outputs of similar age from Journal of Biological Chemistry
#515
of 727 outputs
Altmetric has tracked 12,366,242 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 53,824 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 727 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.