help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Ghosh, S.
Right arrow Articles by Morris, G. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ghosh, S.
Right arrow Articles by Morris, G. F.
American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 890-897, (2002)
© 2002 American Thoracic Society

Original Articles

Bleomycin Sensitivity of Mice Expressing Dominant-Negative p53 in the Lung Epithelium

Sushmita Ghosh, Tamra Mendoza, Luis A. Ortiz, Gary W. Hoyle, Cesar D. Fermin, Arnold R. Brody, Mitchell Friedman and Gilbert F. Morris

Program in Lung Biology, Section of Pulmonary Diseases, Critical Care and Environmental Medicine; and Department of Pathology, Tulane/Xavier Center for Bioenvironmental Research and Tulane Cancer Center, New Orleans, Louisiana

Correspondence and requests for reprints should be addressed to Gilbert F. Morris, Department of Pathology, SL-79, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70118. E-mail: gmorris2{at}tulane.edu

The chemotherapeutic drug bleomycin causes DNA damage and apoptosis in the lungs of mice within hours of endotracheal instillation followed by inflammation and fibrosis weeks later. The p53 tumor suppressor protein mediates cellular responses to DNA damage, including induction of apoptosis, but the effects of p53 activation in the various cell types of the lung during bleomycin-induced pulmonary fibrosis remain unclear. We show here that a transgene with a dominant-negative mutant form of human p53 expressed from the surfactant protein C promoter sensitizes mice to bleomycin-induced lung injury. The bleomycin-exposed transgenic animals display more severe lung pathology with associated collagen deposition and more pronounced lung eosinophilia than simultaneously exposed nontransgenic littermates. These observations suggest that compromising p53 function in the alveolar epithelium impairs recovery of the lung from bleomycin-induced injury.

Key Words: p53 • bleomycin • pulmonary fibrosis • transgenic mice




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Shetty, J. Padijnayayveetil, T. Tucker, D. Stankowska, and S. Idell
The fibrinolytic system and the regulation of lung epithelial cell proteolysis, signaling, and cellular viability
Am J Physiol Lung Cell Mol Physiol, December 1, 2008; 295(6): L967 - L975.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Shetty, P. Shetty, S. Idell, T. Velusamy, Y. P. Bhandary, and R. S. Shetty
Regulation of Plasminogen Activator Inhibitor-1 Expression by Tumor Suppressor Protein p53
J. Biol. Chem., July 11, 2008; 283(28): 19570 - 19580.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
V. Panduri, S. Surapureddi, S. Soberanes, S. A. Weitzman, N. Chandel, and D. W. Kamp
P53 Mediates Amosite Asbestos-Induced Alveolar Epithelial Cell Mitochondria-Regulated Apoptosis
Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 443 - 452.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
M. E. Loewen and G. W. Forsyth
Structure and Function of CLCA Proteins
Physiol Rev, July 1, 2005; 85(3): 1061 - 1092.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
W. E. Lawson, V. V. Polosukhin, O. Zoia, G. T. Stathopoulos, W. Han, D. Plieth, J. E. Loyd, E. G. Neilson, and T. S. Blackwell
Characterization of Fibroblast-specific Protein 1 in Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 899 - 907.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
L. Wang, L. Bowman, Y. Lu, Y. Rojanasakul, R. R. Mercer, V. Castranova, and M. Ding
Essential role of p53 in silica-induced apoptosis
Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L488 - L496.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
H Miyazaki, K Kuwano, K Yoshida, T Maeyama, M Yoshimi, M Fujita, N Hagimoto, R Yoshida, and Y Nakanishi
The perforin mediated apoptotic pathway in lung injury and fibrosis
J. Clin. Pathol., December 1, 2004; 57(12): 1292 - 1298.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
G. F. Morris, A. R. Notwick, O. David, C. Fermin, A. R. Brody, and M. Friedman
Development of Lung Tumors in Mutant p53-Expressing Mice After Inhalation Exposure to Asbestos
Chest, May 1, 2004; 125(5_suppl): 85S - 86S.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Tuberculosis, Lung Infections, Interstitial Lung Disease, and Journalology in AJRCCM 2002
Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 345 - 355.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2002 American Thoracic Society 		  ATS Clinical Skills Tests