scholarly journals Effect of melatonin on EGF- and VEGF-induced monolayer permeability of HUVECs

2019 ◽  
Vol 316 (5) ◽  
pp. H1178-H1191 ◽  
Author(s):  
Ling Yang ◽  
Yujie Zhang ◽  
Yadong Ma ◽  
Jun Du ◽  
Luo Gu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Tyrosine Phosphorylation ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
Phosphatidylinositol 3 Kinase ◽  
Human Umbilical Vein ◽  
Monolayer Permeability ◽  
Umbilical Vein Endothelial Cells

Melatonin is a natural hormone involved in the regulation of circadian rhythm, immunity, and cardiovascular function. In the present study, we focused on the mechanism of melatonin in the regulation of vascular permeability. We found that melatonin could inhibit both VEGF- and EGF-induced monolayer permeability of human umbilical vein endothelial cells (HUVECs) and change the tyrosine phosphorylation of vascular-endothelial (VE-)cadherin, which was related to endothelial barrier function. In addition, phospho-AKT (Ser473) and phospho-ERK(1/2) played significant roles in the regulation of VE-cadherin phosphorylation. Both the phosphatidylinositol 3-kinase/AKT inhibitor LY49002 and MEK/ERK inhibitor U0126 could inhibit the permeability of HUVECs, but with different effects on tyrosine phosphorylation of VE-cadherin. Melatonin can influence the two growth factor-induced phosphorylation of AKT (Ser473) but not ERK(1/2). Our results show that melatonin can inhibit growth factor-induced monolayer permeability of HUVECs by influencing the phosphorylation of AKT and VE-cadherin. Melatonin can be a potential treatment for diseases associated with abnormal vascular permeability. NEW & NOTEWORTHY We found that melatonin could inhibit both EGF- and VEGF-induced monolayer permeability of human umbilical vein endothelial cells, which is related to phosphorylation of vascular-endothelial cadherin. Blockade of phosphatidylinositol 3-kinase/AKT and MEK/ERK pathways could inhibit the permeability of human umbilical vein endothelial cells, and phosphorylation of AKT (Ser473) might be a critical event in the changing of monolayer permeability and likely has cross-talk with the MEK/ERK pathway.

scholarly journals FGF-1-dependent proliferative and migratory responses are impaired in senescent human umbilical vein endothelial cells and correlate with the inability to signal tyrosine phosphorylation of fibroblast growth factor receptor-1 substrates.

1996 ◽  
Vol 134 (3) ◽  
pp. 783-791 ◽  
Author(s):  
S Garfinkel ◽  
X Hu ◽  
I A Prudovsky ◽  
G A McMahon ◽  
E M Kapnik ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
Signal Transduction Pathway ◽  
Cell Populations ◽  
Src Tyrosine Kinase ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Senescent cells do not proliferate in response to exogenous growth factors, yet the number and affinity of growth factor receptors on the cell surface appear to be similar to presenescent cell populations. To determine whether a defect in receptor signaling exists, we analyzed human umbilical vein endothelial cells (HUVEC) since HUVEC growth is absolutely dependent upon the presence of FGF. We report that in both presenescent and senescent HUVEC populations, FGF-1 induces the expression of cell cycle-specific genes, suggesting that functional FGF receptor (FGFR) may exist on the surface of these cells. However, the tyrosine phosphorylation of FGFR-1 substrates, Src and cortactin, is impaired in senescent HUVEC, and only the presenescent cell populations exhibit a FGF-1-dependent Src tyrosine kinase activity. Moreover, we demonstrate that senescent HUVEC are unable to migrate in response to FGF-1, and these data correlate with an altered organization of focal adhesion sites. These data suggest that the induction of gene expression is insufficient to promote a proliferative or migratory phenotype in senescent HUVEC and that the attenuation of the FGFR-1 signal transduction pathway may be involved in the inability of senescent HUVEC to proliferate and/or migrate.

scholarly journals KDR activation is crucial for VEGF165-mediated Ca2+mobilization in human umbilical vein endothelial cells

1999 ◽  
Vol 276 (1) ◽  
pp. C176-C181 ◽  
Author(s):  
Sonia A. Cunningham ◽  
Tuan M. Tran ◽  
M. Pia Arrate ◽  
Robert Bjercke ◽  
Tommy A. Brock
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Human Umbilical Vein ◽  
Intracellular Ca ◽  
Umbilical Vein Endothelial Cells

We have prepared a polyclonal mouse antibody directed against the first three immunoglobulin-like domains of the kinase insert domain-containing receptor (KDR) tyrosine kinase. It possesses the ability to inhibit binding of the 165-amino acid splice variant of vascular endothelial cell growth factor (VEGF165) to recombinant KDR in vitro as well as to reduce VEGF165binding to human umbilical vein endothelial cells (HUVEC). These results confirm that the first three immunoglobulin-like domains of KDR are involved in VEGF165interactions. The anti-KDR antibody is able to completely block VEGF165-mediated intracellular Ca2+mobilization in HUVEC. Therefore, it appears that binding of VEGF165to the fms-like tyrosine kinase (Flt-1) in these cells does not translate into a Ca2+response. This is further exemplified by the lack of response to placental growth factor (PlGF), an Flt-1-specific ligand. Additionally, PlGF is unable to potentiate the effects of submaximal concentrations of VEGF165. Surprisingly, the VEGF-PlGF heterodimer was also very inefficient at eliciting a Ca2+signaling event in HUVEC. We conclude that KDR activation is crucial for mobilization of intracellular Ca2+in HUVEC in response to VEGF165.

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