The mechanisms by which Angiopoietin-1 (Ang-1) modulates the survival of human endothelial cells were investigated. Ang-1 inhibited both TNFalpha-induced and serum deprivation-evoked apoptosis, an effect which was associated with attenuation of caspase activation, inhibition of Smac release from the mitochondria, up-regulation of Survivin-1 expression (IAPs member) and a significant activation of the pro-survival PI-3 kinase/AKT pathway. In addition, Ang-1 activated, in a time-dependent fashion, both the anti-apoptotic ERK1/2 and pro-apoptotic p38 MAP kinases. Ang-1-evoked ERK1/2 activation was mediated in part through the PI-3 kinase pathway, whereas both, the PI-3 kinase and ERK1/2 attenuated p38 MAP kinase activation. / We conclude that Ang-1 promotes endothelial cell survival through several pathways including the PI-3 kinase/AKT and ERK1/2 pathways, up-regulation of Survivin-1 as well as inhibition of Smac release and caspase activity. The preferential activation of these anti-apoptotic effects, as opposed to the activation of pro-apoptotic p38 MAP kinase, results in a net survival response.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33771 |
| Date | January 2002 |
| Creators | Harfouche, Rania. |
| Contributors | Dhindsa, R. (advisor), Hussain, S. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001872998, proquestno: MQ78888, Theses scanned by UMI/ProQuest. |
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