Activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway mediates CD151-induced endothelial cell proliferation and cell migration

2007 ◽  
Vol 39 (2) ◽  
pp. 340-348 ◽  
Author(s):  
Zhen-Zhong Zheng ◽  
Zheng-Xiang Liu
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Protein Kinase ◽  
Endothelial Cell Proliferation ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Protein Kinase Akt ◽  
Phosphatidylinositol 3

scholarly journals Activation of the Phosphatidylinositol 3-Kinase/Protein Kinase Akt Pathway Mediates Nitric Oxide-Induced Endothelial Cell Migration and Angiogenesis

2003 ◽  
Vol 23 (16) ◽  
pp. 5726-5737 ◽  
Author(s):  
Koh Kawasaki ◽  
Robert S. Smith ◽  
Chung-Ming Hsieh ◽  
Jianxin Sun ◽  
Julie Chao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Protein Kinase ◽  
Hind Limb ◽  
Soluble Guanylyl Cyclase ◽  
Pi3 Kinase ◽  
Endothelial Cell Migration ◽  
Phosphatidylinositol 3 Kinase ◽  
Protein Kinase Akt

ABSTRACT To test the hypothesis that the phosphatidylinositol 3-kinase (PI3 kinase)/protein kinase Akt signaling pathway is involved in nitric oxide (NO)-induced endothelial cell migration and angiogenesis, we treated human and bovine endothelial cells with NO donors, S-nitroso-l-glutathione (GSNO) and S-nitroso-N-penicillamine (SNAP). Both GSNO and SNAP increased Akt phosphorylation and activity, which were blocked by cotreatment with the PI3 kinase inhibitor wortmannin. The mechanism was due to the activation of soluble guanylyl cyclase because 8-bromo-cyclic GMP activated PI3 kinase and the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ) blocked NO-induced PI3 kinase activity. Indeed, transfection with adenovirus containing endothelial cell NO synthase (eNOS) or protein kinase G (PKG) increased endothelial cell migration, which was inhibited by cotransfection with a dominant-negative mutant of PI3 kinase (dnPI3 kinase). In a rat model of hind limb ischemia, adenovirus-mediated delivery of human eNOS cDNA in adductor muscles resulted in time-dependent expression of recombinant eNOS, which was accompanied by significant increases in regional blood perfusion and capillary density. Coinjection of adenovirus carrying dnPI3 kinase abolished neovascularization in ischemic hind limb induced by eNOS gene transfer. These findings indicate that NO promotes endothelial cell migration and neovascularization via cGMP-dependent activation of PI3 kinase and suggest that this pathway is important in mediating NO-induced angiogenesis.

scholarly journals Semaphorin 4D/Plexin-B1 Induces Endothelial Cell Migration through the Activation of PYK2, Src, and the Phosphatidylinositol 3-Kinase-Akt Pathway

2005 ◽  
Vol 25 (16) ◽  
pp. 6889-6898 ◽  
Author(s):  
John R. Basile ◽  
Talayeh Afkhami ◽  
J. Silvio Gutkind
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Tyrosine Kinase ◽  
Axonal Guidance ◽  
Endothelial Cell Migration ◽  
Akt Pathway ◽  
Tyrosine Kinase Domain ◽  
Phosphatidylinositol 3 Kinase ◽  
Semaphorin 4D ◽  
Phosphatidylinositol 3

ABSTRACT Semaphorins are cell surface and secreted proteins that provide axonal guidance in neuronal tissues and regulate cell motility in many cell types. They act by binding a family of transmembrane receptors known as plexins, which belong to the c-Met family of scatter factor receptors but lack an intrinsic tyrosine kinase domain. Interestingly, we have recently shown that Plexin-B1 is highly expressed in endothelial cells and that its activation by Semaphorin 4D elicits a potent proangiogenic response (J. R. Basile, A. Barac, T. Zhu, K. L. Guan, and J. S. Gutkind, Cancer Res. 64:5212-5224, 2004). In searches for the underlying molecular mechanism, we observed that Semaphorin 4D-stimulated endothelial cell migration requires the activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Surprisingly, we found that Plexin-B1 stimulates PI3K-Akt through the activation of an intracellular tyrosine kinase cascade that involves the sequential activation of PYK2 and Src. This results in the tyrosine phosphorylation of Plexin-B1, the rapid recruitment of a multimeric signaling complex that includes PYK2, Src, and PI3K to Plexin-B1 and the activation of Akt. These findings suggest that Plexin-B1 may achieve its numerous physiological functions through the direct activation of intracellular tyrosine kinase cascades.

Possible roles of neuropeptide Y Y3-receptor subtype in rat aortic endothelial cell proliferation under hypoxia, and its specific signal transduction

2007 ◽  
Vol 293 (2) ◽  
pp. H959-H967 ◽  
Author(s):  
Zhi-Yong Chen ◽  
Guo-Gang Feng ◽  
Kimitoshi Nishiwaki ◽  
Yasuhiro Shimada ◽  
Yoshihiro Fujiwara ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Neuropeptide Y ◽  
Endothelial Cell Proliferation ◽  
Phosphatidylinositol 3 Kinase ◽  
Large Molecules ◽  
Kinase C ◽  
Phosphatidylinositol 3 ◽  
Aortic Endothelial

The present study was undertaken to determine whether neuropeptide Y (NPY) induces proliferation of rat aortic endothelial cells (RAECs). Since NPY increased the permeability of RAEC monolayers to large molecules via the NPY Y3 receptor, RAEC proliferation has been evaluated in terms of NPY-receptor subtypes and also intracellular mechanisms. RAECs were incubated with gases containing 20, 15, or 10% O2 and a certain amount of N2, depending on the O2 content in 5% CO2 incubators. NPY (10−9–10−6 M) increased the RAEC numbers under hypoxic conditions, such as 15 or 10% O2. Peptide YY elicited no proliferative effect on RAEC, and NPY-(18-36) inhibited the NPY-induced increase in cell number, suggesting that NPY increases the RAEC count through the NPY Y3 receptor. Pertussis toxin, U-73122, GF-109203X, myristorylated autocamtide-2-related inhibitory peptide, and wortmannin inhibited the NPY-induced proliferation of RAEC concentration dependently. DY9760e little affected the proliferation caused by NPY. ML-9 and imatinib actually enhanced the NPY-induced proliferation of cells. These results indicated that the NPY Y3 receptor is coupled with Gi protein, and that NPY-induced increases in RAEC proliferation are mediated by phospholipase C-protein kinase C and/or phosphatidylinositol 3-kinase pathways. In intracellular Ca2+-calmodulin-dependent pathways, calmodulin-dependent protein kinase II partly participates in the NPY-induced cell proliferation. Regarding the previously reported effect of NPY on the permeability of RAEC monolayers to large molecules, it is probable that protein kinase C and phosphatidylinositol 3-kinase pathways are activated for both permeability and cell proliferation induced by NPY under hypoxia, relevant to new insights into the roles of NPY in ischemia-hypoxia.

scholarly journals Gold Nanoparticles Inhibit VEGF165-Induced Migration and Tube Formation of Endothelial Cells via the Akt Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yunlong Pan ◽  
Qing Wu ◽  
Li Qin ◽  
Jiye Cai ◽  
Bin Du
Keyword(s):  
Gold Nanoparticles ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Umbilical Vein ◽  
Critical Role ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
Akt Pathway

The early stages of angiogenesis can be divided into three steps: endothelial cell proliferation, migration, and tube formation. Vascular endothelial growth factor (VEGF) is considered the most important proangiogenic factor; in particular, VEGF165plays a critical role in angiogenesis. Here, we evaluated whether gold nanoparticles (AuNPs) could inhibit the VEGF165-induced human umbilical vein endothelial cell (HUVEC) migration and tube formation. AuNPs and VEGF165were coincubated overnight at 4°C, after which the effects on cell migration and tube formation were assessed. Cell migration was assessed using a modified wound-healing assay and a transwell chamber assay; tube formation was assessed using a capillary-like tube formation assay and a chick chorioallantoic membrane (CAM) assay. We additionally detected the cell surface morphology and ultrastructure using atomic force microscopy (AFM). Furthermore, Akt phosphorylation downstream of VEGFR-2/PI3K in HUVECs was determined in a Western blot analysis. Our study demonstrated that AuNPs significantly inhibited VEGF165-induced HUVEC migration and tube formation by affecting the cell surface ultrastructure, cytoskeleton and might have inhibited angiogenesis via the Akt pathway.

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