PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression

Weisong Zhou, Dustin R. Dowell, Mark W. Geraci, Timothy S. Blackwell, Robert D. Collins, Vasiliy V. Polosukhin, William E. Lawson, Pingsheng Wu, Thomas Sussan, Shyam Biswal, Kasia Goleniewska, Jamye O'Neal, Dawn C. Newcomb, Shinji Toki, Jason D. Morrow, Jr Stokes Peebles

Research output: Contribution to journalArticle

Abstract

The mortality rate for acute lung injury (ALI) is reported to be between 35-40%, and there are very few treatment strategies that improve the death rate from this condition. Previous studies have suggested that signaling through the prostaglandin (PG) I 2 receptor may protect against bleomycin-induced ALI in mice. We found that mice that overexpress PGI synthase (PGIS) in the airway epithelium were significantly protected against bleomycin-induced mortality and had reduced parenchymal consolidation, apoptosis of lung tissue, and generation of F 2-isoprostanes compared with littermate wild-type controls. In addition, we show for the first time in both in vivo and in vitro experiments that PGI 2 induced the expression of NADP (H): quinoneoxidoreductase 1 (Nqo 1), an enzyme that prevents the generation of reactive oxygen species. PGI 2 induction of Nqo 1 provides a possible novel mechanism by which this prostanoid protects against bleomycin-induced mortality and identifies a potential therapeutic target for human ALI.

Original languageEnglish (US)
Pages (from-to)L615-L622
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number4
DOIs
StatePublished - Oct 1 2011

Keywords

  • Epithelial cells
  • Lung
  • NAD(P)H: Quinoneoxidoreductase 1
  • Prostaglandin I

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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  • Cite this

    Zhou, W., Dowell, D. R., Geraci, M. W., Blackwell, T. S., Collins, R. D., Polosukhin, V. V., Lawson, W. E., Wu, P., Sussan, T., Biswal, S., Goleniewska, K., O'Neal, J., Newcomb, D. C., Toki, S., Morrow, J. D., & Stokes Peebles, J. (2011). PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression. American Journal of Physiology - Lung Cellular and Molecular Physiology, 301(4), L615-L622. https://doi.org/10.1152/ajplung.00224.2010