The cAMP effectors PKA and Epac activate endothelial NO synthase through PI3K/Akt pathway in human endothelial cells

2017 ◽  
Vol 145 ◽  
pp. 94-101 ◽  
Author(s):  
Verónica García-Morales ◽  
María Luaces-Regueira ◽  
Manuel Campos-Toimil
Keyword(s):  
Endothelial Cells ◽  
No Synthase ◽  
Akt Pathway ◽  
Human Endothelial Cells ◽  
Endothelial No Synthase

Alterations in the activity and expression of endothelial NO synthase in aged human endothelial cells

2010 ◽  
Vol 131 (2) ◽  
pp. 119-123 ◽  
Author(s):  
Hyun Joong Yoon ◽  
Sang Wook Cho ◽  
Bong Whan Ahn ◽  
Sung Yeul Yang
Keyword(s):  
Endothelial Cells ◽  
No Synthase ◽  
Human Endothelial Cells ◽  
Endothelial No Synthase

scholarly journals Endothelial NO Synthase-Dependent S-Nitrosylation of β-Catenin Prevents Its Association with TCF4 and Inhibits Proliferation of Endothelial Cells Stimulated by Wnt3a

2017 ◽  
Vol 37 (12) ◽  
Author(s):  
Ying Zhang ◽  
Rony Chidiac ◽  
Chantal Delisle ◽  
Jean-Philippe Gratton
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Transcriptional Activity ◽  
No Synthase ◽  
Endothelial Cell Proliferation ◽  
Dependent Manner ◽  
Endothelial No Synthase ◽  
Binding Interface ◽  
Critical Residue

ABSTRACT Nitric oxide (NO) produced by endothelial NO synthase (eNOS) modulates many functions in endothelial cells. S-nitrosylation (SNO) of cysteine residues on β-catenin by eNOS-derived NO has been shown to influence intercellular contacts between endothelial cells. However, the implication of SNO in the regulation of β-catenin transcriptional activity is ill defined. Here, we report that NO inhibits the transcriptional activity of β-catenin and endothelial cell proliferation induced by activation of Wnt/β-catenin signaling. Interestingly, induction by Wnt3a of β-catenin target genes, such as the axin2 gene, is repressed in an eNOS-dependent manner by vascular endothelial growth factor (VEGF). We identified Cys466 of β-catenin as a target for SNO by eNOS-derived NO and as the critical residue for the repressive effects of NO on β-catenin transcriptional activity. Furthermore, we observed that Cys466 of β-catenin, located at the binding interface of the β-catenin–TCF4 transcriptional complex, is essential for disruption of this complex by NO. Importantly, Cys466 of β-catenin is necessary for the inhibitory effects of NO on Wnt3a-stimulated proliferation of endothelial cells. Thus, our data define the mechanism responsible for the repressive effects of NO on the transcriptional activity of β-catenin and link eNOS-derived NO to the modulation by VEGF of Wnt/β-catenin-induced endothelial cell proliferation.

scholarly journals Functional Relevance of Golgi- and Plasma Membrane-Localized Endothelial NO Synthase in Reconstituted Endothelial Cells

2006 ◽  
Vol 26 (5) ◽  
pp. 1015-1021 ◽  
Author(s):  
Qian Zhang ◽  
Jarrod E. Church ◽  
Davin Jagnandan ◽  
John D. Catravas ◽  
William C. Sessa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasma Membrane ◽  
No Synthase ◽  
Endothelial No Synthase ◽  
Functional Relevance

Characterization and localization of endothelial nitric oxide synthase using specific monoclonal antibodies

1993 ◽  
Vol 265 (5) ◽  
pp. C1379-C1387 ◽  
Author(s):  
J. S. Pollock ◽  
M. Nakane ◽  
L. D. Buttery ◽  
A. Martinez ◽  
D. Springall ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
No Synthase ◽  
Endothelial No Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We have produced specific monoclonal antibodies (MAb) against particulate bovine aortic endothelial nitric oxide synthase. In Western blots, native and cultured bovine aortic endothelial cells as well as cultured bovine microvascular endothelial cells possess immunoreactive NO synthase. In dot blots, MAb H210 and H32 detect 1 ng and 100 pg of purified endothelial NO synthase, respectively. Both antibodies are specific to the endothelial NO synthase and do not cross-react with other known isoforms of NO synthase, namely from the brain, from cytokine/endotoxin-induced macrophages, or from cytokine/endotoxin-induced vascular smooth muscle cells. Immunohistochemical studies demonstrated the specificity of endothelial NO synthase for endothelial cells in various bovine and human tissues. Many types of endothelial cells, macrovascular, microvascular, arterial, and venous were found to possess this specific isoform of NO synthase. Electron microscopy showed the enzyme to be associated with the plasma membrane, membranes of cytoplasmic vesicles, and in the cytoplasm in human umbilical vein endothelial cells. The results demonstrate that particulate endothelial NO synthase is present in a site to act rapidly to produce NO for release into the blood or toward the smooth muscle in many vascular beds.

scholarly journals High-glucose incubation of human umbilical-vein endothelial cells does not alter expression and function either of G-protein α-subunits or of endothelial NO synthase

1996 ◽  
Vol 315 (1) ◽  
pp. 281-287 ◽  
Author(s):  
Gudrun MANCUSI ◽  
Caroline HUTTER ◽  
Sabina BAUMGARTNER-PARZER ◽  
Kurt SCHMIDT ◽  
Wolfgang SCHÜTZ ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
G Protein ◽  
High Glucose ◽  
Umbilical Vein ◽  
No Synthase ◽  
Functional Changes ◽  
Endothelial No Synthase ◽  
Umbilical Vein Endothelial Cells ◽  
And Function ◽  
Cells Cultured

Alterations in G-protein-controlled signalling pathways (primarily pathways controlled by Gs and Gi) have been reported to occur in animal models of diabetes mellitus. We have therefore studied the effect of a long-term exposure of human umbilical vein endothelial cells to elevated concentrations of glucose on expression and function of G-protein subunits and endothelial NO synthase. Long-term incubation in high glucose (30 mM for 15 days) did not affect the levels of Giα-2, Gqα, the splice variants (long and short form) of Gsα, and the G-protein β-subunits or adenylate cyclase activity: basal, as well as isoprenaline-, forskolin- and guanosine 5´-[γ-thio]triphosphate-stimulated enzyme activities were comparable in high- and low-glucose-treated cells, thus ruling out any functional changes in the stimulatory pathway. Pretreatment of endothelial cells with pertussis toxin blocked a substantial fraction (50%) of the mitogenic response to serum factor(s) which depend(s) on functional Gi2. The sensitivity of cells cultured in high glucose was comparable with that of the paired controls maintained in normal glucose (EC50 = 3.1±0.5 and 3.3±0.4 ng/ml respectively). Similarly, we failed to detect any differences in endothelial NO synthase expression, or intracellular distribution and basal activity of the enzyme in endothelial cells cultured in high glucose. Stimulation of NO synthase in intact cells revealed a comparable response to the calcium ionophore (A23187). In contrast, stimulation with histamine (which acts via H1-receptors predominantly coupled to Gq) resulted in a significantly increased response in the cells maintained in high glucose. These data are suggestive of an altered H1-histamine receptor–Gq–phospholipase C pathway in endothelial cells cultured in high glucose concentrations, but rule out any glucose-induced functional changes in Gs- and Gi-controlled signalling pathways.

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