Xanthine Oxidase Interaction with Vascular Endothelial Growth Factor in Human Endothelial Cell Angiogenesis
| Autor: | Jinsong Ni, Baijun Kou, Donald R. J. Singer, Manu Vatish |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Vascular Endothelial Growth Factor A
Umbilical Veins Xanthine Oxidase Cell Survival MAP Kinase Signaling System Physiology Angiogenesis Neovascularization Physiologic Oxypurinol Apoptosis Biology Xanthine p38 Mitogen-Activated Protein Kinases Phosphatidylinositol 3-Kinases chemistry.chemical_compound Physiology (medical) Humans Enzyme Inhibitors Phosphorylation Xanthine oxidase Molecular Biology Protein kinase B Cells Cultured Matrigel Microcirculation Endothelial Cells Cell biology Vascular endothelial growth factor Endothelial stem cell Vascular endothelial growth factor A chemistry Vascular endothelial growth factor C Reactive Oxygen Species Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-akt Cell Division |
| Zdroj: | Microcirculation. 15:251-267 |
| ISSN: | 1549-8719 1073-9688 |
| DOI: | 10.1080/10739680701651495 |
| Popis: | Reduced capillary density occurs early in cardiovascular diseases. Oxidant stress is implicated in endothelial apoptosis. We investigated the effects of xanthine oxidase (XO) on endothelial survival signaling: protein kinase B/Akt, its cross-talk with p38 MAPK and apoptosis pathways, and its effect on vascular tube formation in vascular endothelial growth factor (VEGF)-simulated human umbilical vein cells.We studied primary cultured human endothelial cells from the umbilical cord. Reactive oxygen species (ROS) production was detected by dihydroethidium staining, cell-signaling pathways by western blots, cell survival by western blots, and nuclear chromatin and angiogenesis response by MTT proliferation assay and three-dimensional Matrigel cultures.Exogenous XO increased cellular ROS production and caused superoxide-dependent inhibition of Akt phosphorylation and enhancement of p38 MAPK phosphorylation in a time-and dose-dependent manner. In contrast, application of the XO inhibitor oxypurinol or allopurinol inhibited VEGF-stimulated Akt phosphorylation, indicating that endogenous XO promotes VEGF-induced endothelial cell (EC) survival signaling. Exogenous XO induced activation of caspase-3 and reduced expression of the anti-apoptosis protein Bcl-2. Exogenous XO also reduced EC viability, proliferation, and vascular tube formation by p38 MAPK-dependent, phosphoinositide 3-kinase (PI3-K) reversible mechanisms; whereas VEGF promoted EC survival by PI3-K-dependent, p38 MAPK-independent effects.Exogenous XO activity is an important contributor to endothelial mechanisms for microvascular rarefaction, by modulation of cell survival signaling pathways; however, endogenous XO is necessary for maintaining EC survival. |
| Databáze: | OpenAIRE |
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