help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on June 15, 2007, doi:10.1165/rcmb.2006-0376OC

Am. J. Respir. Cell Mol. Biol., Volume 37, Number 4, October 2007, 405-413

A more recent version of this article appeared on October 1, 2007
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2006-0376OCv1
37/4/405    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 Tipple, T. E
Right arrow Articles by Smith, C. V
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tipple, T. E
Right arrow Articles by Smith, C. V

Submitted on October 6, 2006
Revised on June 11, 2007

Thioredoxin-Related Mechanisms in Hyperoxic Lung Injury in Mice

Trent E Tipple1*, Stephen E Welty1, Lynette K Rogers1, Thomas N Hansen2, Young-Eun Choi3, James P Kehrer4, and Charles V Smith2

1 Department of Pediatrics, Division of Neonatology, Columbus Children's Hospital, The Ohio State University College of Medicine, Center for Perinatal Research, Columbus Children's Research Institute, Columbus, OH, USA, 2 Center for Developmental Pharmacology and Toxicology, Children's Hospital and Regional Medical Center, Seattle, WA, USA, 3 Division of Pharmacology and Toxicology, The University of Texas at Austin, College of Pharmacy, Austin, TX, USA, 4 Washington State University, College of Pharmacy, Pullman, WA, USA

* To whom correspondence should be addressed. E-mail: tipplet{at}pediatrics.ohio-state.edu.

Reduction of glutathione disulfide (GSSG) to glutathione (GSH) by glutathione reductase (GR) enhances the efficiency of GSH-dependent antioxidant activities. However, GR-deficient (a1Neu) mice are less susceptible to acute lung injury from continuous exposure to >95% O2 (96 h: 6.9±0.1g right lung/kg body vs room air 3.6±0.3) than are C3H/HeN control mice (10.6±1.3 vs 4.2±0.3, p<0.001). a1Neu mice have greater hepatic thioredoxin (Trx)1 and Trx2 levels than do C3H/HeN mice, suggesting compensation for the absence of GR. a1Neu mice exposed to hyperoxia for 96 h showed lower levels of inflammatory infiltrates in lungs than did similarly exposed C3H/HeN mice. Pretreatment with aurothioglucose (ATG), a thioredoxin reductase (TrxR) inhibitor, exacerbated the effects of hyperoxia on lung injury in a1Neu mice (11.6±0.8, p<0.001), but attenuated hyperoxic lung edema and inflammation in C3H/HeN mice (6.3±0.4, p<0.001). No consistent alterations were observed in lung GSH contents or liver GSH or GSSG levels following ATG pretreatment. The data suggest that modulation of Trx/TrxR systems might provide therapeutically useful alterations of cellular resistance to oxidant stresses. The protective effects of ATG against hyperoxic lung injury could prove to be particularly useful therapeutically.




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. M. Heyob, L. K. Rogers, and S. E. Welty
Glutathione Reductase Targeted to Type II Cells Does Not Protect Mice from Hyperoxic Lung Injury
Am. J. Respir. Cell Mol. Biol., December 1, 2008; 39(6): 683 - 688.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2007 American Thoracic Society. 		  2009/2010 ATS Fellows Career Development Awards