Signaling and Regulation of Endothelial Cell Survival by Angiopoietin-2.
From: Rm. L3.05, Critical Care Division, Royal Victoria Hospital, 687 Pine Ave West, Montreal, Quebec, Canada.
American journal of physiology. Heart and circulatory physiology
- Publish Date: Oct 2006
- ISSN: 0363-6135
- Volume: 291
- Issue: 4
- Pages: H1635-45
- Medium: Print
- Language: English
- Citation (JAMA): Harfouche Rania, Hussain Sabah N A, et al. Signaling and Regulation of Endothelial Cell Survival by Angiopoietin-2.. Am. J. Physiol. Heart Circ. Physiol. Oct 2006;291:H1635-45
Abstract
Angiopoietins are ligands for endothelial cell-specific Tie-2 receptors. Whereas angiopoietin-1 (Ang-1) activates these receptors and promotes cell survival, migration, and sprouting, little information is available regarding how 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 phosphatidylinositol 3 (PI3)-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 PI3-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.
Mesh Headings (Keywords): 1-Phosphatidylinositol 3-Kinase, Angiopoietin-2, Apoptosis, Cell Movement, Cell Survival, Cells, Cultured, Endothelial Cells, Endothelium, Vascular, Humans, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Phosphorylation, Proto-Oncogene Proteins c-akt, Receptors, TIE, Signal Transduction, Vascular Endothelial Growth Factor A
Check for Full Text / PubMed Unique Identifier (PMID): 16714355
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