AJP - Lung Columbus Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 283: L766-L776, 2002. First published May 3, 2002; doi:10.1152/ajplung.00250.2000
1040-0605/02 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
283/4/L766    most recent
00250.2000v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
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 Web of Science (23)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jean, J. C.
Right arrow Articles by Joyce-Brady, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jean, J. C.
Right arrow Articles by Joyce-Brady, M.
Vol. 283, Issue 4, L766-L776, October 2002

gamma -Glutamyl transferase deficiency results in lung oxidant stress in normoxia

Jyh Chang Jean1, Yue Liu1, Lou Ann Brown2, Robert E. Marc3, Elizabeth Klings1, and Martin Joyce-Brady1

1 Pulmonary Center at Boston University School of Medicine, Boston, Massachusetts 02118; 2 Department of Pediatrics, Emory University, Atlanta, Georgia 30322; and 3 Moran Eye Center, University of Utah, Salt Lake City, Utah 84108

gamma -Glutamyl transferase (GGT) is critical to glutathione homeostasis by providing substrates for glutathione synthesis. We hypothesized that loss of GGT would cause oxidant stress in the lung. We compared the lungs of GGTenu1 mice, a genetic model of GGT deficiency, with normal mice in normoxia to study this hypothesis. We found GGT promoter 3 (P3) alone expressed in normal lung but GGT P3 plus P1, an oxidant-inducible GGT promoter, in GGTenu1 lung. Glutathione content was barely decreased in GGTenu1 lung homogenate and elevated nearly twofold in epithelial lining fluid, but the fraction of oxidized glutathione was increased three- and fourfold, respectively. Glutathione content in GGTenu1 alveolar macrophages was decreased nearly sixfold, and the oxidized glutathione fraction was increased sevenfold. Immunohistochemical studies showed glutathione deficiency together with an intense signal for 3-nitrotyrosine in nonciliated bronchiolar epithelial (Clara) cells and expression of heme oxygenase-1 in the vasculature only in GGTenu1 lung. When GGTenu1 mice were exposed to hyperoxia, survival was decreased by 25% from control because of accelerated formation of vascular pulmonary edema, widespread oxidant stress in the epithelium, diffuse depletion of glutathione, and severe bronchiolar cellular injury. These data indicate a critical role for GGT in lung glutathione homeostasis and antioxidant defense in normoxia and hyperoxia.

glutathione; heme oxygenase-1; 3-nitrotyrosine


This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
H. Zhang and H. J. Forman
Redox Regulation of {gamma}-Glutamyl Transpeptidase
Am. J. Respir. Cell Mol. Biol., November 1, 2009; 41(5): 509 - 515.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
A R Bentley, P Emrani, and P A Cassano
Genetic variation and gene expression in antioxidant related enzymes and risk of COPD: a systematic review
Thorax, November 1, 2008; 63(11): 956 - 961.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. H. Lowry, B. P. McAllister, J.-C. Jean, L. A. S. Brown, R. P. Hughey, W. W. Cruikshank, S. Amar, E. C. Lucey, K. Braun, P. Johnson, et al.
Lung Lining Fluid Glutathione Attenuates IL-13-Induced Asthma
Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 509 - 516.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Bellmeyer, J. M. Martino, N. S. Chandel, G. R. Scott Budinger, D. A. Dean, and G. M. Mutlu
Leptin Resistance Protects Mice from Hyperoxia-induced Acute Lung Injury
Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 587 - 594.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
D. S. Lee, J. C. Evans, S. J. Robins, P. W. Wilson, I. Albano, C. S. Fox, T. J. Wang, E. J. Benjamin, R. B. D'Agostino, and R. S. Vasan
Gamma Glutamyl Transferase and Metabolic Syndrome, Cardiovascular Disease, and Mortality Risk: The Framingham Heart Study
Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 127 - 133.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J.-C. Jean, C. B. Rich, and M. Joyce-Brady
Hypoxia results in an HIF-1-dependent induction of brain-specific aldolase C in lung epithelial cells
Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L950 - L956.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
H. Zhang, H. Liu, K. E. Iles, R.-M. Liu, E. M. Postlethwait, Y. Laperche, and H. J. Forman
4-Hydroxynonenal Induces Rat {gamma}-Glutamyl Transpeptidase through Mitogen-Activated Protein Kinase-Mediated Electrophile Response Element/Nuclear Factor Erythroid 2-Related Factor 2 Signaling
Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 174 - 181.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
V L Kinnula
Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases
Thorax, August 1, 2005; 60(8): 693 - 700.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online