AJP - Lung Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol (April 23, 2004). doi:10.1152/ajplung.00359.2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/2/L393    most recent
00359.2003v1
Right arrow Alert me when this article is cited
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 Flaherty, D. M.
Right arrow Articles by Hunninghake, G. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Flaherty, D. M.
Right arrow Articles by Hunninghake, G. W.
Submitted on October 16, 2003
Accepted on April 19, 2004

ADENOVIRUS VECTORS ACTIVATE SURVIVAL PATHWAYS IN LUNG EPITHELIAL CELLS

Dawn M. Flaherty1*, Sara L. Hinde1, Martha M. Monick1, Linda S. Powers1, Mary A. Bradford1, Timur Yarovinsky1, and Gary W. Hunninghake1

1 Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA; Department of Internal Medicine, Veterans Affairs Medical Center, Iowa City, Iowa, USA

* To whom correspondence should be addressed. E-mail: flahertydm{at}mail.medicine.uiowa.edu.

Airway epithelial cells are often the sites of targeted adenovirus vector delivery. Activation of the host inflammatory response and modulation of signal transduction pathways by adenovirus vectors have been previously documented, including activation of MAP kinases and phosphatidylinositol 3-kinase (PI3-kinase). The effect of activation of these pathways by adenovirus vectors on cell survival has not been examined. Both the PI3-kinase/Akt and ERK/MAP kinase signaling pathways have been linked to cell survival. Akt has been found to play a role in cell survival and apoptosis through its downstream effects on apoptosis-related proteins. Constitutive activation of either PI3- kinase or Akt blocks apoptosis induced by c-Myc, UV radiation, TGF-{beta}, Fas and RSV infection. We examined the effect of Ad vector infection on activation of these prosurvival pathways and its downstream consequences. Airway epithelial cells were transduced with replication-deficient adenoviral vectors containing a nonspecific transgene, Green Fluorescent Protein (Ad GFP), driven by the CMV promoter or an empty vector with no transgene (AdEV). They were then exposed to the pro-apoptotic stimulus actinomycin-D plus TNF-{alpha} and evidence of apoptosis was evaluated. As compared to the cells treated with actinomycin/TNF alone, the adenovirus vector-infected cells had a 50% reduction in apoptosis. When we examined induction of the pro-survival pathways, ERK and AKT, in the viral vector-infected cells, we found that there was significant activation of both Akt and ERK.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
Z. Wang, T. Mitsui, M. Ishida, and J. Arita
Adenovirus vectors differentially modulate proliferation of pituitary lactotrophs in primary culture in a mitogen and infection time-dependent manner
J. Endocrinol., July 1, 2008; 198(1): 209 - 217.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
K. Miller-Jensen, K. A. Janes, Y.-L. Wong, L. G. Griffith, and D. A. Lauffenburger
Adenoviral vector saturates Akt pro-survival signaling and blocks insulin-mediated rescue of tumor-necrosis-factor-induced apoptosis
J. Cell Sci., September 15, 2006; 119(18): 3788 - 3798.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
Q. Liu, L. R. White, S. A. Clark, D. J. Heffner, B. W. Winston, L. A. Tibbles, and D. A. Muruve
Akt/Protein Kinase B Activation by Adenovirus Vectors Contributes to NF{kappa}B-Dependent CXCL10 Expression
J. Virol., December 1, 2005; 79(23): 14507 - 14515.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M. S. Rajala, R. V. S. Rajala, R. A. Astley, A. L. Butt, and J. Chodosh
Corneal Cell Survival in Adenovirus Type 19 Infection Requires Phosphoinositide 3-Kinase/Akt Activation
J. Virol., October 1, 2005; 79(19): 12332 - 12341.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.