Journal of Applied Physiology Millar Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

J Appl Physiol (May 12, 2005). doi:10.1152/japplphysiol.01105.2004
This Article
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
99/3/1226    most recent
01105.2004v1
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
Services
Right arrow Email this article to a friend
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 Chess, P. R.
Right arrow Articles by Finkelstein, J. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chess, P. R.
Right arrow Articles by Finkelstein, J. N.
Submitted on October 1, 2004
Accepted on May 5, 2005

Reactive oxidant and p42/44 MAP kinase signaling is necessary for mechanical strain-induced proliferation in pulmonary epithelial cells

Patricia R. Chess1*, Michael A. O'Reilly2, Fredrick Sachs3, and Jacob N. Finkelstein2

1 Department of Pediatrics, University of Rochester, Rochester, NY, USA; Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA
2 Department of Pediatrics, University of Rochester, Rochester, NY, USA; Department of Environmental Medicine, University of Rochester, Rochester, NY, USA
3 Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY, USA

* To whom correspondence should be addressed. E-mail: patricia_chess{at}urmc.rochester.edu.

Mechanical strain is necessary for normal lung growth and development. Individuals with respiratory failure are supported with mechanical ventilation, leading to altered lung growth and injury. Understanding signaling pathways initiated by mechanical strain in lung epithelial cells will help guide development of strategies aimed at optimizing strain-induced lung growth while mitigating ventilator-induced lung injury. To study strain-induced proliferative signaling, focusing on the role of reactive oxidant species (ROS) and p42/44 MAP kinase, human pulmonary epithelial H441 and MLE15 cells were exposed to equibiaxial cyclic mechanical strain. ROS were increased within 15 minutes of strain. N -acetylcysteine inactivated strain-induced ROS and inhibited p42/44 MAP kinase phosphorylation and strain-induced proliferation. PD98059 and UO126, p42/44 MAP kinase inhibitors, blocked strain-induced proliferation. To verify the specificity of p42/44 MAP kinase inhibition, cells were transfected with dominant negative MEK1 plasmid DNA. Transfected cells did not proliferate in response to mechanical strain. To determine if strain-induced tyrosine kinase activity is necessary for strain-induced ROS- p42/44 MAP kinase signaling, genistein, a tyrosine kinase inhibitor, was used. Genistein did not block strain-induced ROS production or p42/44 MAP kinase phosphorylation. Gadolinium, a mechanosensitive calcium channel blocker, blocked strain-induced ROS production and p42/44 MAP kinase phosphorylation, but not straininduced tyrosine phosphorylation. This data support ROS production and p42/44 MAP kinase phosphorylation being involved in a common strain-induced signaling pathway, necessary for straininduced proliferation in pulmonary epithelial cells, with a parallel strain-induced tyrosine kinase pathway.




This article has been cited by other articles:


Home page
 J Biomol ScreenHome page
V. S. Nirmalanandhan and G. S. Sittampalam
Stem Cells in Drug Discovery, Tissue Engineering, and Regenerative Medicine: Emerging Opportunities and Challenges
J Biomol Screen, August 1, 2009; 14(7): 755 - 768.
[Abstract] [PDF]

Home page
 J. Biol. Chem.Home page
C. P. Gayer, L. S. Chaturvedi, S. Wang, D. H. Craig, T. Flanigan, and M. D. Basson
Strain-induced Proliferation Requires the Phosphatidylinositol 3-Kinase/AKT/Glycogen Synthase Kinase Pathway
J. Biol. Chem., January 23, 2009; 284(4): 2001 - 2011.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Jin, R. M. Ray, and L. R. Johnson
TNF-{alpha}/cycloheximide-induced apoptosis in intestinal epithelial cells requires Rac1-regulated reactive oxygen species
Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G928 - G937.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Papaiahgari, A. Yerrapureddy, S. R. Reddy, N. M. Reddy, J. M. Dodd-O, M. T. Crow, D. N. Grigoryev, K. Barnes, R. M. Tuder, M. Yamamoto, et al.
Genetic and Pharmacologic Evidence Links Oxidative Stress to Ventilator-induced Lung Injury in Mice
Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1222 - 1235.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
L. S. Chaturvedi, H. M. Marsh, and M. D. Basson
Src and focal adhesion kinase mediate mechanical strain-induced proliferation and ERK1/2 phosphorylation in human H441 pulmonary epithelial cells
Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1701 - C1713.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. Papaiahgari, A. Yerrapureddy, P. M. Hassoun, J. G. N. Garcia, K. G. Birukov, and S. P. Reddy
EGFR-Activated Signaling and Actin Remodeling Regulate Cyclic Stretch-Induced NRF2-ARE Activation
Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 304 - 312.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1948 by the American Physiological Society.