Major Shifts in the Spatio-Temporal Distribution of Lung Antioxidant Enzymes during Influenza Pneumonia
Name
Yamada-2012-Major shifts in the.pdf
Size
2.89 MB
Format
Adobe PDF
Checksum (MD5)
48d8d3ae7ff0159538c5ae8a686f6a67
Author(s)
Yamada, Yoshiyuki
Limmon, Gino V.
Zheng, Dahai
Li, Na
Li, Liang
Yin, Lu
Chow, Vincent T. K.
Chen, Jianzhu
Engelward, Bevin P
Date Issued
February 2012
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Yamada, Yoshiyuki et al. “Major Shifts in the Spatio-Temporal Distribution of Lung Antioxidant Enzymes During Influenza Pneumonia.” Ed. Roger Le Grand. PLoS ONE 7.2 (2012): e31494. Web.
Version
Final published version
Abstract
With the incessant challenge of exposure to the air we breathe, lung tissue suffers the highest levels of oxygen tension and thus requires robust antioxidant defenses. Furthermore, following injury or infection, lung tissue faces the additional challenge of inflammation-induced reactive oxygen and nitrogen species (ROS/RNS). Little is known about the identity or distribution of lung antioxidant enzymes under normal conditions or during infection-induced inflammation. Using a mouse model of influenza (H1N1 influenza virus A/PR/8/34 [PR8]) in combination with bioinformatics, we identified seven lung-abundant antioxidant enzymes: Glutathione peroxidase 3 (Gpx3), Superoxide dismutase 3 (Sod3), Transferrin (Tf), peroxyredoxin6 (Prdx6), glutathione S-transferase kappa 1 (Gstk1), Catalase (Cat), and Glutathione peroxidase 8 (Gpx8). Interestingly, despite the demand for antioxidants during inflammation, influenza caused depletion in two key antioxidants: Cat and Prdx6. As Cat is highly expressed in Clara cells, virus-induced Clara cell loss contributes to the depletion in Cat. Prdx6 is also reduced due to Clara cell loss, however there is a coincident increase in Prdx6 levels in the alveoli, resulting in only a subtle reduction of Prdx6 overall. Analogously, Gpx3 shifts from the basement membranes underlying the bronchioles and blood vessels to the alveoli, thus maintaining balanced expression. Taken together, these studies identify key lung antioxidants and reveal their distribution among specific cell types. Furthermore, results show that influenza depletes key antioxidants, and that in some cases there is coincident increased expression, consistent with compensatory expression. Given that oxidative stress is known to be a key risk factor during influenza infection, knowledge about the antioxidant repertoire of lungs, and the spatio-temporal distribution of antioxidants, contributes to our understanding of the underlying mechanisms of influenza-induced morbidity and mortality.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Singapore-MIT Alliance in Research and Technology (SMART)
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pone.0031494
