scholarly journals X-Linked Inhibitor of Apoptosis Protein Is an Important Regulator of Vascular Endothelial Growth Factor–Dependent Bovine Aortic Endothelial Cell Survival

2008 ◽  
Vol 102 (8) ◽  
pp. 896-904 ◽  
Author(s):  
Jongmin Kim ◽  
Jongbong Park ◽  
Seungmin Choi ◽  
Sung-Gil Chi ◽  
Amy L. Mowbray ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Inhibitor Of Apoptosis ◽  
Bovine Aortic Endothelial Cell ◽  
Vascular Endothelial ◽  
Inhibitor Of Apoptosis Protein ◽  
Endothelial Cell Survival ◽  
Apoptosis Protein ◽  
Important Regulator ◽  
Endothelial Growth Factor

X-Linked Inhibitor of Apoptosis Protein (XIAP) Supports Urokinase (uPA)-Induced Endothelial Cell Survival

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5461-5461
Author(s):  
Gerald W Prager ◽  
Judit Mihaly ◽  
Patrick Brunner ◽  
Christoph Zielinski ◽  
Bernd Binder
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Cell Survival ◽  
Endothelial Cell Migration ◽  
Migration And Invasion ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Endothelial Cell Survival ◽  
Apoptosis Protein

Abstract High uPA expressing tumors are associated with poor prognosis. While a direct effect on tumor cell behavior is described, uPA has especially been shown to mediate (tumor-) angiogenesis. Originally, the urokinase system has been implicated to assist the angiogenic process by it’s proteolytic activities. It is now becoming increasingly evident that uPA additionally elicits a whole array pro-angiogenic responses like differentiation, proliferation and cell migration, independent of its proteolytic activity by inducing intracellular signal transduction. Here we show that uPA induces upregulation of inhibitor of apoptosis proteins (IAPs), which protects endothelial cells against apoptosis. Thereby, uPA-induced endothelial cell survival is mediated by transcriptional upregulation the X-linked inhibitor of apoptosis protein (XIAP), because downregulation of XIAP by small interfering RNA techniques significantly reduces uPA mediated cell survival efficiencies of uPA in endothelial cells. The antiapoptotic activity of uPA was dependent on the presence of uPAR and LRP, but independent of the PI3kinase pathway, while VEGF-dependent antiapoptosis is mainly PI3kinase dependent. uPA-induced cell survival is dependent on the type of extracellular matrix on which cells are attached used indicating the involvement of integrin adhesion receptors. TherebyConsistently, uPA induces phosphorylation of the CDC42 downstream effector p21-activated kinase 1 (PAK1), which leads to IkappaB kinase alpha (IKKa) phosphorylation, a prerequisite for NFkappaB activation. As a consequence, p52/p50 but not p65 is are translocated into the nucleus. Blocking NFkappaB by using the specific NFkappaB inhibitor BAY 11–7082 or by adenoviral-mediated overexpression of its inhibitor, IkB, inhibits uPA-induced XIAP expression as well as uPA-induced cell survival. From these data we conclude that uPA, which is a main player in endothelial cell migration and invasion, provides an additional, PI3-kinase independent but NFkappaB dependent cell survival mechanism.

Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein

Blood ◽  
2009 ◽  
Vol 113 (6) ◽  
pp. 1383-1390 ◽  
Author(s):  
Gerald W. Prager ◽  
Judit Mihaly ◽  
Patrick M. Brunner ◽  
Yuri Koshelnick ◽  
Gunilla Hoyer-Hansen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Survival ◽  
Pi3 Kinase ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Mrna Stabilization ◽  
Endothelial Cell Survival ◽  
Iκb Kinase ◽  
Apoptosis Protein

AbstractUrokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic responses, such as differentiation, proliferation, and migration. In this study, we demonstrate that in endothelial cells uPA also protects against apoptosis by transcriptional up-regulation and partially by mRNA stabilization of inhibitor of apoptosis proteins, most prominently the X-linked inhibitor of apoptosis protein (XIAP). The antiapoptotic activity of uPA was dependent on its protease activity, the presence of uPA receptor (uPAR) and low-density lipoprotein receptor-related protein (LRP), but independent of the phosphatidylinositol 3 (PI3) kinase pathway, whereas vascular endothelial growth factor (VEGF)–induced antiapoptosis was PI3 kinase dependent. uPA-induced cell survival involved phosphorylation of p21-activated kinase 1 (Pak1) and the IκB kinase α that leads to nuclear factor κB (NF-κB) p52 activation. Indeed, blocking NF-κB activation by using specific NF-κB inhibitors abolished uPA-induced cell survival as it blocked uPA-induced XIAP up-regulation. Furthermore, down-regulating XIAP expression by small interfering RNA (siRNA) significantly reduced uPA-dependent endothelial cell survival. This mechanism is also important for VEGF-induced antiapoptosis because VEGF-dependent up-regulation of XIAP was found defective in uPA−/− endothelial cells. This led us to conclude that uPA is part of a novel NF-κB–dependent cell survival pathway.

Vascular Endothelial Growth Factor Enhances Endothelial Cell Survival and Tumor Radioresistance

2002 ◽  
Vol 8 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Vinay K. Gupta ◽  
Nora T. Jaskowiak ◽  
Michael A. Beckett ◽  
Helena J. Mauceri ◽  
Jeremy Grunstein ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Cell Survival ◽  
Vascular Endothelial ◽  
Endothelial Cell Survival ◽  
Endothelial Growth Factor

198 microRNA-17 As The Target of Immobilized Vascular Endothelial Growth Factor in Endothelial Cell Survival Under Ischaemic Conditions

Heart ◽  
2016 ◽  
Vol 102 (Suppl 6) ◽  
pp. A133-A134
Author(s):  
Sezin Aday ◽  
Marie Besnier ◽  
Janet Zoldan ◽  
Laura Carreto ◽  
Jaimy Saif ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Cell Survival ◽  
Vascular Endothelial ◽  
Endothelial Cell Survival ◽  
Endothelial Growth Factor
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