scholarly journals Vitamin E enhances the acylation of 1-O-alkyl-sn-glycero-3-phosphocholine in human endothelial cells

1994 ◽  
Vol 298 (1) ◽  
pp. 115-119 ◽  
Author(s):  
K Tran ◽  
A F D'Angelo ◽  
P C Choy ◽  
A C Chan
Keyword(s):  
Endothelial Cells ◽  
Vitamin E ◽  
Platelet Activating Factor ◽  
Enzyme Substrate ◽  
Cell Homogenate ◽  
Transacylase Activity ◽  
Dose Dependent ◽  
Phospholipid Pool ◽  
Indirect Stimulation

1-O-Alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) is the precursor of platelet-activating factor. It is formed via the CoA-independent transacylase reaction, which transfers the polyenoyl acyl group from the sn-2 position of a diacyl phospholipid to the sn-2 position of 1-O-alkyl-sn-glycero-3-phosphocholine (alkyl-GPC). We have reported previously that vitamin E alters phospholipid turnover in the endothelial cells by increasing arachidonic acid release and prostacyclin synthesis. In the present study, the role of vitamin E in the formation of alkylacyl-GPC was investigated. Incubation of endothelial cells with vitamin E resulted in an increase in the formation of [3H]alkylacyl-GPC from [3H]alkyl-GPC. The effect of vitamin E was dose-dependent at concentrations below 23 microM. However, vitamin E did not have a direct effect on the transacylase activity. When endothelial cells were incubated with vitamin E, the CoA-independent transacylase activity in the cell homogenate was found to be enhanced. Kinetic analysis of the transacylase activity in the pre-incubated cells showed that the enhancement of enzyme activity was at the enzyme-substrate level. When endothelial cells were incubated with vitamin E analogues (Trolox, tocol and tocopherol acetate), only limited enhancement of the transacylation process was detected. It is clear that vitamin E enhanced the synthesis of alkylacyl-GPC from alkyl-GPC in a very specific manner by an indirect stimulation of the CoA-independent transacylase activity. The regulation by vitamin E of the formation of alkylacyl-GPC may mediate the transfer of arachidonate from the diacyl phospholipid pool into the ether-linked phospholipid pool.

The Role of Platelet-Activating Factor in Endothelial Cells

1990 ◽  
Vol 64 (01) ◽  
pp. 099-103 ◽  
Author(s):  
Stephen M Prescott ◽  
Thomas M McIntyre ◽  
Guy A Zimmerman
Keyword(s):  
Endothelial Cells ◽  
Platelet Activating Factor

scholarly journals GAS6 Inhibits Granulocyte Adhesion to Endothelial Cells

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2334-2340
Author(s):  
Gian Carlo Avanzi ◽  
Margherita Gallicchio ◽  
Flavia Bottarel ◽  
Loretta Gammaitoni ◽  
Giuliana Cavalloni ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Platelet Activating Factor ◽  
Polymorphonuclear Cells ◽  
Vascular Endothelial ◽  
Tnf Α ◽  
High Concentrations ◽  
Adhesive Interactions ◽  
Factor Α ◽  
Dose Dependent

GAS6 is a ligand for the tyrosine kinase receptors Rse, Axl, and Mer, but its function is poorly understood. Previous studies reported that both GAS6 and Axl are expressed by vascular endothelial cells (EC), which play a key role in leukocyte extravasation into tissues during inflammation through adhesive interactions with these cells. The aim of this work was to evaluate the GAS6 effect on the adhesive function of EC. Treatment of EC with GAS6 significantly inhibited adhesion of polymorphonuclear cells (PMN) induced by phorbol 12-myristate 13-acetate (PMA), platelet-activating factor (PAF), thrombin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but not that induced by FMLP and IL-8. GAS6 did not affect adhesion to resting EC. Titration experiments showed that high concentrations of GAS6 were needed to inhibit PMN adhesion and that inhibition was dose-dependent at the concentration range of 0.1 to 1 μg/mL. One possibility was that high concentrations were needed to overwhelm the effect of endogenous GAS6 produced by EC. In line with this possibility, treatment of resting EC with soluble Axl significantly potentiated PMN adhesion. Analysis of localization of GAS6 by confocal microscopy and cytofluorimetric analysis showed that it is concentrated along the plasma membrane in resting EC and treatment with PAF induces depletion and/or redistribution of the molecule. These data suggest that GAS6 functions as a physiologic antiinflammatory agent produced by resting EC and depleted when proinflammatory stimuli turn on the proadhesive machinery of EC.

scholarly journals Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

2007 ◽  
Vol 67 (24) ◽  
pp. 11906-11913 ◽  
Author(s):  
L.-F. Dong ◽  
E. Swettenham ◽  
J. Eliasson ◽  
X.-F. Wang ◽  
M. Gold ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Vitamin E ◽  
Induction Of Apoptosis

scholarly journals Wegener's Granulomatosis: Anti–proteinase 3 Antibodies Are Potent Inductors of Human Endothelial Cell Signaling and Leakage Response

1998 ◽  
Vol 187 (4) ◽  
pp. 497-503 ◽  
Author(s):  
Ulf Sibelius ◽  
Katja Hattar ◽  
Angelika Schenkel ◽  
Thomas Noll ◽  
Elena Csernok ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Wegener’S Granulomatosis ◽  
Inositol Phosphates ◽  
Vascular Endothelial Cells ◽  
Platelet Activating Factor ◽  
Barrier Properties ◽  
Wegener's Granulomatosis ◽  
Phosphoinositide Hydrolysis ◽  
Proteinase 3 ◽  
Dose Dependent

Anti–neutrophil cytoplasmic antibodies (ANCAs) targeting proteinase 3 (PR3) have a high specifity for Wegener's granulomatosis (WG), and their role in activating leukocytes is well appreciated. In this study, we investigated the influence of PR3-ANCA and murine monoclonal antibodies on human umbilical vascular endothelial cells (HUVECs). Priming of HUVECs with tumor necrosis factor α induced endothelial upregulation of PR3 message and surface expression of this antigen, as measured by Cyto-ELISA, with a maximum occurrence after 2 h. Primed cells responded to low concentrations of both antibodies (25 ng–2.5 μg/ml), but not to control immunoglobulins, with pronounced, dose-dependent phosphoinositide hydrolysis, as assessed by accumulation of inositol phosphates. The signaling response peaked after 20 min, in parallel with the appearance of marked prostacyclin and platelet-activating factor synthesis. The F(ab)2 fragment of ANCA was equally potent as ANCA itself. Disrupture of the endothelial F-actin content by botulinum C2 toxin to avoid antigen–antibody internalization did not affect the response. In addition to the metabolic events, anti-PR3 challenge, in the absence of plasma components, provoked delayed, dose-dependent increase in transendothelial protein leakage. We conclude that anti-PR3 antibodies are potent inductors of the preformed phosphoinositide hydrolysis–related signal tranduction pathway in human endothelial cells. Associated metabolic events and the loss of endothelial barrier properties suggest that anti-PR3–induced activation of endothelial cells may contribute to the pathogenetic sequelae of autoimmune vasculitis characterizing WG.

scholarly journals Histamine induces interleukin-8 secretion by endothelial cells

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2229-2233 ◽  
Author(s):  
P Jeannin ◽  
Y Delneste ◽  
P Gosset ◽  
S Molet ◽  
P Lassalle ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Histamine Receptor ◽  
Leukotriene B4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Delayed Effects ◽  
Allergic Disorders ◽  
Dose Dependent

It has been shown that histamine induces early changes on endothelial cells (EC), such as a transient expression of P-selectin and secretion and/or surface expression of early mediators (eg, prostacyclin [PG1(2)], platelet-activating factor [PAF], and leukotriene B4 [LTB4]). However, delayed effects of histamine on EC and particularly on cytokine production are undefined. In this study, the effect of histamine on interleukin (IL)-8 production by EC was evaluated using an enzyme-linked immunosorbent assay (ELISA) method and mRNA expression. The results showed that histamine increased the secretion and the mRNA expression of IL-8 by EC. Histamine-induced IL-8 production was (1) dose-dependent (at a dose > or = 10(-6) mol/L), (2) potentialized by costimulation with tumor necrosis factor (TNF)-alpha, (3) inhibited by H1 or H2 histamine receptor antagonists, and (4) significantly increased 4 hours after the initial stimulation. These data suggest that histamine may be involved in the control of the late inflammatory reaction associated to allergic disorders through IL-8 secretion by EC.

Role of nitric oxide and superoxide anion in spontaneous lung chemiluminescence

1997 ◽  
Vol 272 (2) ◽  
pp. L262-L267 ◽  
Author(s):  
M. L. Barnard ◽  
B. Robertson ◽  
B. P. Watts ◽  
J. F. Turrens
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Light Emission ◽  
No Synthase ◽  
O2 Concentration ◽  
Dose Dependent Fashion ◽  
Spontaneous Chemiluminescence ◽  
Oxidant Production ◽  
Dose Dependent

Inhibition of nitric oxide (.NO) synthase by nitro-L-arginine (NLA) decreased baseline chemiluminescence in a dose-dependent fashion up to 78% at 300 microM NLA. This inhibition was prevented by pretreatment with 1 mM arginine. Similarly, addition of superoxide dismutase (SOD; 200 U/ml) to the perfusion buffer inhibited spontaneous light emission by 57%. Addition of NLA after SOD or vice versa did not inhibit light emission any further, suggesting that both .NO and O2.- were precursors of the same oxidant. Production of additional extracellular O2.- by neutrophils activated with phorbol 12-myristate 13-acetate increased light emission by >200%, but this increase was insensitive to NLA. Increasing the intracellular steady-state O2.- concentration by perfusion of control lungs with the Cu and Zn-containing SOD inhibitor diethyldithiocarbamate (1 mM) stimulated light emission up to fourfold, but this spontaneous chemiluminescence was also insensitive to NLA. In experiments using cultured endothelial cells supplemented with extracellular bovine serum albumin (BSA), 5 microM of the Ca2+ ionophore A-23187 (a stimulant of .NO synthase) stimulated chemiluminescence by 40%. This increase was again SOD and NLA sensitive. Addition of NLA after SOD or vice versa did not change light emission. These results suggest that the background chemiluminescence of isolated-perfused intact lungs may result from the constant release of small amounts of O2.- and .NO by endothelial cells into the capillary lumen, which in turn react with BSA in the perfusion buffer.

scholarly journals Age-related Beta-synuclein Alters the p53/Mdm2 Pathway and Induces the Apoptosis of Brain Microvascular Endothelial Cells In Vitro

2018 ◽  
Vol 27 (5) ◽  
pp. 796-813 ◽  
Author(s):  
Katrin Brockhaus ◽  
Michael R. R. Böhm ◽  
Harutyun Melkonyan ◽  
Solon Thanos
Keyword(s):  
Endothelial Cells ◽  
Neurodegenerative Diseases ◽  
Microvascular Endothelial Cells ◽  
Mrna Levels ◽  
Brain Microvascular Endothelial Cells ◽  
Age Related ◽  
Microvascular Endothelial ◽  
Dose Dependent

Increased β-synuclein (Sncb) expression has been described in the aging visual system. Sncb functions as the physiological antagonist of α-synuclein (Snca), which is involved in the development of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases. However, the exact function of Sncb remains unknown. The aim of this study was to elucidate the age-dependent role of Sncb in brain microvascular endothelial cells (BMECs). BMECs were isolated from the cortices of 5- to 9-d-old Sprague-Dawley rats and were cultured with different concentrations of recombinant Sncb (rSncb) up to 72 h resembling to some degree age-related as well as pathophysiological conditions. Viability, apoptosis, expression levels of Snca, and the members of phospholipase D2 (Pld2)/ p53/ Mouse double minute 2 homolog (Mdm2)/p19(Arf) pathway, response in RAC-alpha serine/threonine-protein kinase (Akt), and stress-mediating factors such as heme oxygenase (decycling) 1 (Hmox) and Nicotinamide adenine dinucleotide phosphate oxygenase 4 (Nox4) were examined. rSncb-induced effects were confirmed through Sncb small interfering RNA (siRNA) knockdown in BMECs. We demonstrated that the viability decreases, while the rate of apoptosis underly dose-dependent alterations. For example, apoptosis increases in BMECs following the treatment with higher dosed rSncb. Furthermore, we observed a decrease in Snca immunostaining and messenger RNA (mRNA) levels following the exposure to higher rScnb concentrations. Akt was shown to be downregulated and pAkt upregulated by this treatment, which was accompanied by a dose-independent increase in p19(Arf) levels and enhanced intracellular Mdm2 translocation in contrast to a dose-dependent p53 activation. Moreover, Pld2 activity was shown to be induced in rSncb-treated BMECs. The expression of Hmox and Nox4 after Sncb treatment was altered on BEMCs. The obtained results demonstrate dose-dependent effects of Sncb on BMECs in vitro. For example, the p53-mediated and Akt-independent apoptosis together with the stress-mediated response of BMECs related to exposure of higher SNCB concentrations may reflect the increase in Sncb with duration of culture as well as its impact on cell decay. Further studies, expanding on the role of Sncb, may help understand its role in the neurodegenerative diseases.

scholarly journals S-nitrosylation of VASP at cysteine 64 mediates the inflammation-stimulated increase in microvascular permeability

2017 ◽  
Vol 313 (1) ◽  
pp. H66-H71 ◽  
Author(s):  
Patricia Zamorano ◽  
Natalie Marín ◽  
Francisco Córdova ◽  
Alejandra Aguilar ◽  
Cynthia Meininger ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Platelet Activating Factor ◽  
Endothelial Permeability ◽  
Subcellular Location ◽  
Membrane Reconstitution ◽  
Barrier Integrity ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
In Cells

We tested the hypothesis that platelet-activating factor (PAF) induces S-nitrosylation of vasodilator-stimulated phosphoprotein (VASP) as a mechanism to reduce microvascular endothelial barrier integrity and stimulate hyperpermeability. PAF elevated S-nitrosylation of VASP above baseline levels in different endothelial cells and caused hyperpermeability. To ascertain the importance of endothelial nitric oxide synthase (eNOS) subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S-nitrosylation of VASP in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Reconstitution of VASP knockout myocardial endothelial cells with cysteine mutants of VASP demonstrated that S-nitrosylation of cysteine 64 is associated with PAF-induced hyperpermeability. We propose that regulation of VASP contributes to endothelial cell barrier integrity and to the onset of hyperpermeability. S-nitrosylation of VASP inhibits its function in barrier integrity and leads to endothelial monolayer hyperpermeability in response to PAF, a representative proinflammatory agonist. NEW & NOTEWORTHY Here, we demonstrate that S-nitrosylation of vasodilator-stimulated phosphoprotein (VASP) on C64 is a mechanism for the onset of platelet-activating factor-induced hyperpermeability. Our results reveal a dual role of VASP in endothelial permeability. In addition to its well-documented function in barrier integrity, we show that S-nitrosylation of VASP contributes to the onset of endothelial permeability.

scholarly journals Synthesis of platelet-activating factor by endothelial cells. The role of G proteins.

1990 ◽  
Vol 265 (26) ◽  
pp. 15550-15559 ◽  
Author(s):  
R.E. Whatley ◽  
D.F. Fennell ◽  
J.A. Kurrus ◽  
G.A. Zimmerman ◽  
T.M. McIntyre ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
G Proteins ◽  
Platelet Activating Factor
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