JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by West, J. A. A.
Right arrow Articles by Plopper, C. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by West, J. A. A.
Right arrow Articles by Plopper, C. G.

Vol. 294, Issue 2, 516-523, August 2000

Elevated Airway GSH Resynthesis Confers Protection to Clara Cells from Naphthalene Injury in Mice Made Tolerant by Repeated Exposures1

Jay A. A. West, Alan R. Buckpitt and Charles G. Plopper

Department of Anatomy, Physiology, and Cell Biology (J.A.A.W., C.G.P.) and Department of Molecular Biosciences (A.R.B.), School of Veterinary Medicine, University of California, Davis, California

Repeated exposures to Clara cell cytotoxicants, such as naphthalene (NA), render target cell populations resistant to further acute injury. Previous studies suggest that alterations in bioactivation enzymes in target sites (bronchioles) of tolerant mice are insufficient to account for the marked reduction in susceptibility. Mice were made tolerant by seven daily injections of NA. GSH in the terminal airways was 2.7-fold greater in tolerant mice than in vehicle controls and a NA (300 mg/kg) challenge dose did not produce injury. Tolerant mice, allowed to recuperate for 96 h after the seventh NA injection, were again susceptible to NA injury, and terminal airway GSH levels had declined to control levels. To determine whether alterations in GSH resynthesis account for tolerance, the activity of gamma -glutamylcysteine synthetase (gamma -GCS) was measured or mice were treated with a combination of buthionine sulfoximine (BSO), a gamma -GCS inhibitor, and NA. gamma -GCS activity was elevated in resistant airways of tolerant mice. Tolerant mice treated with both BSO and NA appeared as susceptible to injury as NA-challenged controls. We conclude that GSH is critical for Clara cell resistance to NA injury in tolerant mice because: 1) GSH levels in target airways from NA-tolerant animals are elevated; 2) after a 96-h recuperation period, tolerant mice had lower GSH levels and are again susceptible to NA injury; 3) alterations in the activity of gamma -GCS correspond with changes in susceptibility to NA injury; and 4) inhibition of gamma -GCS with BSO increases susceptibility to NA injury in tolerant mice.

1 Research funding was provided by National Institute of Environmental Health Sciences (NIEHS) Grants ES 04311, ES06700, and ES04699. University of California, Davis, is an NIEHS Center for Environmental Health Sciences (ES05707), and support for core facilities provided by the Center and used in this work is gratefully acknowledged.

0022-3565/00/2942-0516$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. J. Homer, Z. Zhu, L. Cohn, C. G. Lee, W. I. White, S. Chen, and J. A. Elias
Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation
Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L502 - L511.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
C. Hofmann, C. Putz, B. Semder, T. H. Faller, G. A. Csanady, and J. G. Filser
Styrene-7,8-Oxide Burden in Ventilated, Perfused Lungs of Mice and Rats Exposed to Vaporous Styrene
Toxicol. Sci., March 1, 2006; 90(1): 39 - 48.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. D. Vassallo, S. M. Hicks, S. L. Born, and G. P. Daston
Roles for Epoxidation and Detoxification of Coumarin in Determining Species Differences in Clara Cell Toxicity
Toxicol. Sci., November 1, 2004; 82(1): 26 - 33.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
G. L. Baker, M. A. Shultz, M. V. Fanucchi, D. M. Morin, A. R. Buckpitt, and C. G. Plopper
Assessing Gene Expression in Lung Subcompartments Utilizing In Situ RNA Preservation
Toxicol. Sci., January 1, 2004; 77(1): 135 - 141.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. A. A. West, L. S. Van Winkle, D. Morin, C. A. Fleschner, H. J. Forman, and C. G. Plopper
Repeated Inhalation Exposures to the Bioactivated Cytotoxicant Naphthalene (NA) Produce Airway-Specific Clara Cell Tolerance in Mice
Toxicol. Sci., September 1, 2003; 75(1): 161 - 168.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. D. Reynolds, P. R. Reynolds, G. S. Pryhuber, J. D. Finder, and B. R. Stripp
Secretoglobins SCGB3A1 and SCGB3A2 Define Secretory Cell Subsets in Mouse and Human Airways
Am. J. Respir. Crit. Care Med., December 1, 2002; 166(11): 1498 - 1509.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. A. A. West, K. J. Williams, E. Toskala, S. J. Nishio, C. A. Fleschner, H. J. Forman, A. R. Buckpitt, and C. G. Plopper
Induction of Tolerance to Naphthalene in Clara Cells Is Dependent on a Stable Phenotypic Adaptation Favoring Maintenance of the Glutathione Pool
Am. J. Pathol., March 1, 2002; 160(3): 1115 - 1127.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics.