help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on February 4, 2005, doi:10.1165/rcmb.2004-0314OC

Am. J. Respir. Cell Mol. Biol., Volume 32, Number 5, May 2005, 395-403

A more recent version of this article appeared on May 1, 2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2004-0314OCv1
32/5/395    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 Krick, S.
Right arrow Articles by Rose, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Krick, S.
Right arrow Articles by Rose, F.

Submitted on October 5, 2004
Revised on February 4, 2005

Role of HIF-1{alpha} in hypoxia-induced apoptosis of primary alveolar epithelial type II cells

Stefanie Krick1*, Bastian G Eul1, Jorg Hanze1, Rajkumar Savai1, Friedrich Grimminger1, Werner Seeger1, and Frank Rose1

1 Department of Internal Medicine/Pulmonary and Critical Care Medicine, Justus-Liebig University, Giessen, Germany

* To whom correspondence should be addressed. E-mail: Stefanie.Krick{at}innere.med.uni-giessen.de.

Hypoxia affects alveolar homeostasis and may induce epithelial injury, which has been implicated in lung diseases such as fibrosis. The underlying cellular and molecular mechanisms are, however, largely unknown. Primary rat alveolar epithelial type II cells (ATII) exposed to graded hypoxia for 24 and 48 h caused a dose-dependent induction of cell cycle arrest and suppression of proliferation, comparable to the effects of angiotensin II, a potent inducer of ATII cell death. Hypoxia-induced changes in ATII homeostasis are thought to proceed primarily via activation of hypoxia inducible factor (HIF-1{alpha}), since hypoxia increased HIF-1{alpha} protein expression, nuclear translocation and transactivation of its specific DNA binding domain, the hypoxia responsive element (HRE). Under hypoxic conditions, expression of the proapoptotic protein Bnip3L, known to be one of the HIF-1 dependent target genes, was upregulated. Suppression of HIF-1{alpha} or Bnip-3L with small interfering RNA (siRNA) fully blocked the hypoxia-induced apoptosis and Bnip3L expression. Furthermore, overexpression of HIF-1{alpha} by transient transfection enhanced the hypoxia-induced apoptosis. Thus, we conclude that hypoxia suppresses alveolar epithelial cell proliferation and enhances ATII apoptosis through activation of the HIF-1{alpha}/HRE axis and Bnip3L. Targeting HIF-1{alpha} may represent a new strategy which could impede the alveolar denudation in several lung diseases.




This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Tzouvelekis, V. Harokopos, T. Paparountas, N. Oikonomou, A. Chatziioannou, G. Vilaras, E. Tsiambas, A. Karameris, D. Bouros, and V. Aidinis
Comparative Expression Profiling in Pulmonary Fibrosis Suggests a Role of Hypoxia-inducible Factor-1{alpha} in Disease Pathogenesis
Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1108 - 1119.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Miyake, H. Kaise, K.-i. Isono, H. Koseki, K. Kohno, and M. Tanaka
Protective Role of Macrophages in Noninflammatory Lung Injury Caused by Selective Ablation of Alveolar Epithelial Type II Cells
J. Immunol., April 15, 2007; 178(8): 5001 - 5009.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. Bouvry, C. Planes, L. Malbert-Colas, V. Escabasse, and C. Clerici
Hypoxia-Induced Cytoskeleton Disruption in Alveolar Epithelial Cells
Am. J. Respir. Cell Mol. Biol., November 1, 2006; 35(5): 519 - 527.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
T. R. Martin, N. Hagimoto, M. Nakamura, and G. Matute-Bello
Apoptosis and Epithelial Injury in the Lungs
Proceedings of the ATS, October 1, 2005; 2(3): 214 - 220.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2005 American Thoracic Society.