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


     

Am J Physiol Heart Circ Physiol (September 12, 2002). doi:10.1152/ajpheart.00330.2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/1/H92    most recent
00330.2002v1
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 Breslin, J. W
Right arrow Articles by Duran, W. N
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Breslin, J. W
Right arrow Articles by Duran, W. N

Articles in PresS, published online ahead of print September 12, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00330.2002
Submitted on April 15, 2002
Accepted on September 9, 2002

VEGF Increases Endothelial Permeability by Separate Signaling Pathways Involving ERK-1/2 and Nitric Oxide

Jerome W Breslin1, Peter J Pappas2, Joaquim J Cerveira3, Robert W Hobson II2, and Walter N Duran4*

1 Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, NJ, USA
2 Department of Surgery, UMDNJ-New Jersey Medical School, Program in Vascular Biology and Division of Vascular Surgery, Newark, NJ, USA; Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, NJ, USA
3 Department of Surgery, UMDNJ-New Jersey Medical School, Program in Vascular Biology and Division of Vascular Surgery, Newark, NJ, USA
4 Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, NJ, USA; Department of Surgery, UMDNJ-New Jersey Medical School, Program in Vascular Biology and Division of Vascular Surgery, Newark, NJ, USA

* To whom correspondence should be addressed. E-mail: duran{at}umdnj.edu.

We tested the hypothesis that VEGF regulates endothelial hyperpermeability to macromolecules by activating the ERK-1/2 MAP kinase pathway. We also tested whether protein kinase C (PKC) and nitric oxide (NO) mediate VEGF-induced increases in permeability via the ERK-1/2 pathway. FITC-dextran-70 flux across human umbilical vein endothelial cell monolayers served as an index of permeability, while western blots assessed phosphorylation of ERK-1/2. VEGF-induced hyperpermeability was inhibited by antisense DNA oligonucleotides directed against ERK-1/2, and by blockade of MEK and Raf-1 activities (20 µM PD98059 and 5 µM GW5074). These blocking agents also reduced ERK-1/2 phosphorylation. The PKC inhibitor bisindolylmaleimide I (10 µM) blocked both VEGF-induced ERK-1/2 activation and hyperpermeability. The NO synthase (NOS) inhibitor L-NAME (200 µM) and NO scavenger PTIO (100 µM) abolished VEGF-induced hyperpermeability, but did not block ERK-1/2 phosphorylation. These observations demonstrate VEGF-induced hyperpermeability involves activation of PKC, NOS as well as Raf-1, MEK and ERK-1/2. Furthermore, our data suggest that ERK-1/2 and NOS are elements of different signaling pathways in VEGF-induced hyperpermeability.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
F. A. Sanchez, D. D. Kim, R. G. Duran, C. J. Meininger, and W. N. Duran
Internalization of eNOS via caveolae regulates PAF-induced inflammatory hyperpermeability to macromolecules
Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1642 - H1648.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. W. Breslin, N. Gaudreault, K. D. Watson, R. Reynoso, S. Y. Yuan, and M. H. Wu
Vascular endothelial growth factor-C stimulates the lymphatic pump by a VEGF receptor-3-dependent mechanism
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H709 - H718.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. D. Kim, F. A. Sanchez, R. G. Duran, T. Kanetaka, and W. N. Duran
Endothelial nitric oxide synthase is a molecular vascular target for the Chinese herb Danshen in hypertension
Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2131 - H2137.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. T. Flaherty
Sorafenib in Renal Cell Carcinoma
Clin. Cancer Res., January 15, 2007; 13(2): 747s - 752s.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. Mirzapoiazova, I. Kolosova, P. V. Usatyuk, V. Natarajan, and A. D. Verin
Diverse effects of vascular endothelial growth factor on human pulmonary endothelial barrier and migration
Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L718 - L724.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
F. A. Sanchez, N. B. Savalia, R. G. Duran, B. K. Lal, M. P. Boric, and W. N. Duran
Functional significance of differential eNOS translocation
Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1058 - H1064.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
T. Hatakeyama, P. J. Pappas, R. W. Hobson II, M. P. Boric, W. C. Sessa, and W. N. Duran
Endothelial nitric oxide synthase regulates microvascular hyperpermeability in vivo
J. Physiol., July 1, 2006; 574(1): 275 - 281.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. Lamy, M. Blanchette, J. Michaud-Levesque, R. Lafleur, Y. Durocher, A. Moghrabi, S. Barrette, D. Gingras, and R. Beliveau
Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation
Carcinogenesis, May 1, 2006; 27(5): 989 - 996.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
L. A. Edwards, M. Verreault, B. Thiessen, W. H. Dragowska, Y. Hu, J. H.F. Yeung, S. Dedhar, and M. B. Bally
Combined inhibition of the phosphatidylinositol 3-kinase/Akt and Ras/mitogen-activated protein kinase pathways results in synergistic effects in glioblastoma cells.
Mol. Cancer Ther., March 1, 2006; 5(3): 645 - 654.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. H. Tinsley, J. W. Breslin, N. R. Teasdale, and S. Y. Yuan
PKC-dependent, burn-induced adherens junction reorganization and barrier dysfunction in pulmonary microvascular endothelial cells
Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L217 - L223.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. A. Birukova, K. G. Birukov, B. Gorshkov, F. Liu, J. G. N. Garcia, and A. D. Verin
MAP kinases in lung endothelial permeability induced by microtubule disassembly
Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L75 - L84.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
M. H Wu, S. Y Yuan, and H. J Granger
The protein kinase MEK1/2 mediate vascular endothelial growth factor- and histamine-induced hyperpermeability in porcine coronary venules
J. Physiol., February 15, 2005; 563(1): 95 - 104.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
V. Carbajal, M. H. Vargas, E. Flores-Soto, E. Martinez-Cordero, B. Bazan-Perkins, and L. M. Montano
LTD4 induces hyperresponsiveness to histamine in bovine airway smooth muscle: role of SR-ATPase Ca2+ pump and tyrosine kinase
Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L84 - L92.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
H. Aramoto, J. W. Breslin, P. J. Pappas, R. W. Hobson II, and W. N. Duran
Vascular endothelial growth factor stimulates differential signaling pathways in in vivo microcirculation
Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1590 - H1598.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. B. Regard, S. Scheek, T. Borbiev, A. A. Lanahan, A. Schneider, A.-M. Demetriades, H. Hiemisch, C. A. Barnes, A. D. Verin, and P. F. Worley
Verge: A Novel Vascular Early Response Gene
J. Neurosci., April 21, 2004; 24(16): 4092 - 4103.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.