| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medicine, McGill University, Montreal, Canada
* To whom correspondence should be addressed. E-mail: sabah.hussain{at}muhc.mcgill.ca.
Angiopoietins are ligands for endothelial cell-specific Tie-2 receptors. While angiopoietin-1 (Ang-1) activates these receptors and promotes cell survival, migration and sprouting, little information is available regarding how angiopoietin-2 (Ang-2) influences these cells. In this study, we evaluated signaling pathways and biological effects of physiological concentrations of Ang-2 in cultured human umbilical vein endothelial cells. Ang-2 at 150 and 300 ng/ml elicited a transient (reaching peak values within 15 min of exposure) increase in the phosphorylation of Tie-2 receptors, protein kinase B (AKT), Erk1/2 and p38 members of the mitogen activated protein kinases. However, unlike Ang-1, Ang-2 significantly inhibited JNK/SAPK phosphorylation. When vascular endothelial growth factor (VEGF) was present along with Ang-2, Erk1/2 phosphorylation was inhibited whereas augmentation of Ang-1-induced Erk1/2 phosphorylation was triggered by VEGF. Ang-2 treatment had no effect on cell migration and in-vitro wound healing but significantly attenuated serum-deprivation-induced apoptosis and promoted survival. These effects were completely reversed by PI-3 kinase and Erk1/2 inhibitors but were augmented by an inhibitor of the p38 pathway. These results suggest that Ang-2 promotes endothelial cell survival through the Erk1/2 and PI-3 kinase pathways and that this angiopoietin is not a strong promoter of endothelial cell migration. We also conclude that the nature of interactions in terms of Erk1/2 activation between Ang-2 and VEGF is different from that of Ang-1 and VEGF.
This article has been cited by other articles:
|
|
 |
|
  L. Yahiaoui, D. Gvozdic, G. Danialou, M. Mack, and B. J. Petrof CC family chemokines directly regulate myoblast responses to skeletal muscle injury J. Physiol., August 15, 2008; 586(16): 3991 - 4004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Maliba, A. Brkovic, P.-E. Neagoe, L. R. Villeneuve, and M. G. Sirois Angiopoietin-mediated endothelial P-selectin translocation: cell signaling mechanisms J. Leukoc. Biol., February 1, 2008; 83(2): 352 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Tressel, R.-P. Huang, N. Tomsen, and H. Jo Laminar Shear Inhibits Tubule Formation and Migration of Endothelial Cells by an Angiopoietin-2-Dependent Mechanism Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2150 - 2156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Artwohl, K. Muth, K. Kosulin, R. de Martin, T. Holzenbein, G. Rainer, A. Freudenthaler, N. Huttary, L. Schmetterer, W. K. Waldhausl, et al. R-(+)-{alpha}-lipoic acid inhibits endothelial cell apoptosis and proliferation: involvement of Akt and retinoblastoma protein/E2F-1 Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E681 - E689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Brkovic, M. Pelletier, D. Girard, and M. G. Sirois Angiopoietin chemotactic activities on neutrophils are regulated by PI-3K activation J. Leukoc. Biol., April 1, 2007; 81(4): 1093 - 1101. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
