Regulation of Arachidonic Acid Release by Calcium Influx in Human Endothelial Cells

1999 ◽  
Vol 36 (3) ◽  
pp. 235-244 ◽  
Author(s):  
Elisabeth Millanvoye-Van Brussel ◽  
Monique David-Dufilho ◽  
Thuc Do Pham ◽  
Lahcen Iouzalen ◽  
Marie Aude Devynck
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Calcium Influx ◽  
Arachidonic Acid Release ◽  
Human Endothelial Cells ◽  
Acid Release

Ibuprofen protects human endothelial cell prostaglandin H synthase from hydrogen peroxide

1996 ◽  
Vol 271 (6) ◽  
pp. C1879-C1886 ◽  
Author(s):  
D. A. Wessels ◽  
S. L. Hempel
Keyword(s):  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Endothelial Cell ◽  
Arachidonic Acid Release ◽  
Human Endothelial Cells ◽  
Prostaglandin H Synthase ◽  
Cyclooxygenase Activity ◽  
Acid Release ◽  
Prostaglandin H

Human endothelial cells exposed to H2O2 demonstrate decreased prostacyclin (PGI2) synthesis due to decreased prostaglandin H synthase (PGH synthase) activity. We tested the hypothesis that PGH synthase activity could be protected from H2O2 by a reversible nonsteroidal anti-inflammatory drug. Experiments demonstrate that ibuprofen if present during H2O2 exposure, protects endothelial cell PGH synthase against the decrease in prostaglandin formation caused by H2O2. Additional studies demonstrated that decreasing arachidonic acid release from cell phospholipids during H2O2 exposure did not protect PGI2 synthesis following H2O2 exposure. In other experiments, ibuprofen did not chelate Fe2+ in a conformation that inhibited the reactivity of Fe2+. In addition, ibuprofen did not scavenge HO. However, we demonstrate that ibuprofen significantly protects purified PGH synthase cyclooxygenase activity from the effects of H2O2. The results confirm the hypothesis. These findings suggest that ibuprofen displaces oxidant species from the cyclooxygenase site of PGH synthase, thereby preventing oxidation of the functional groups important for PGH synthase activity.

Calcium-independent phospholipase A2 is regulated by a novel protein kinase C in human coronary artery endothelial cells

2005 ◽  
Vol 288 (2) ◽  
pp. C475-C482 ◽  
Author(s):  
Maureen C. Meyer ◽  
Pamela J. Kell ◽  
Michael H. Creer ◽  
Jane McHowat
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Protein Kinase C ◽  
Coronary Artery ◽  
Protein Kinase ◽  
Arachidonic Acid Release ◽  
Human Coronary Artery ◽  
Phospholipid Hydrolysis ◽  
Kinase C ◽  
Acid Release

We demonstrated previously that thrombin stimulation of endothelial cells activates a membrane-associated, Ca2+-independent phospholipase A2 (iPLA2) that selectively hydrolyzes arachidonylated plasmalogen phospholipids. We report that incubation of human coronary artery endothelial cells (HCAEC) with phorbol 12-myristate 13-acetate (PMA) to activate protein kinase C (PKC) resulted in hydrolysis of cellular phospholipids similar to that observed with thrombin stimulation (0.05 IU/ml; 10 min). Thrombin stimulation resulted in a decrease in arachidonylated plasmenylcholine (2.7 ± 0.1 vs. 5.3 ± 0.4 nmol PO4/mg of protein) and plasmenylethanolamine (7.5 ± 1.0 vs. 12.0 ± 0.9 nmol PO4/mg of protein). Incubation with PMA resulted in decreases in arachidonylated plasmenylcholine (3.2 ± 0.3 nmol PO4/mg of protein) and plasmenylethanolamine (6.0 ± 1.0 nmol PO4/mg of protein). Incubation of HCAEC with the selective iPLA2 inhibitor bromoenol lactone (5 mM; 10 min) inhibited accelerated plasmalogen phospholipid hydrolysis in response to both PMA and thrombin stimulation. Incubation of HCAEC with PMA (100 nM; 5 min) resulted in increased arachidonic acid release (7.1 ± 0.3 vs. 1.1 ± 0.1%) and increased production of lysoplasmenylcholine (1.4 ± 0.2 vs. 0.6 ± 0.1 nmol PO4/mg of protein), similar to the responses observed with thrombin stimulation. Downregulation of PKC by prolonged exposure to PMA (100 nM; 24 h) completely inhibited thrombin-stimulated increases in arachidonic acid release (7.1 ± 0.6 to 0.5 ± 0.1%) and lysoplasmenylcholine production (2.0 ± 0.1 to 0.2 ± 0.1 nmol PO4/mg of protein). These data suggest that PKC activates iPLA2 in HCAEC, leading to accelerated plasmalogen phospholipid hydrolysis and increased phospholipid metabolite production.

Influence of growth oxygen level on eicosanoid release from lung endothelial cells during hypoxia

1992 ◽  
Vol 263 (4) ◽  
pp. L454-L459
Author(s):  
W. E. Holden ◽  
E. M. Burnham ◽  
M. A. Lee ◽  
S. P. Bagby
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Acute Hypoxia ◽  
Calcium Ionophore ◽  
Pulmonary Vasculature ◽  
Ionophore A23187 ◽  
Oxygen Level ◽  
Arachidonic Acid Release ◽  
Eicosanoid Release ◽  
Acid Release

Eicosanoid products of arachidonic acid are suspected modulators of hypoxic vasoconstriction in the pulmonary vasculature. Vascular endothelial cells (EC) release several eicosanoids, but there is disagreement regarding the effect of hypoxia on EC eicosanoid release. We postulated that the oxygen level of growth in culture might influence the release of eicosanoids during acute hypoxia. We studied EC cultured from the main pulmonary arteries of pigs and grown at either 5% or near 20% oxygen, representing the normal limits of oxygen exposure to endothelium in normal lungs. Although cultures grown in 5% oxygen grew slightly faster by 4 days, the confluent cell number, protein content, and baseline eicosanoid release were no different compared with paired cultures grown in 20% oxygen. However, with an acute decrease in oxygen level, cultures grown in 5% oxygen released less prostaglandin E2, F2 alpha, and 6-ketoprostaglandin F1 alpha compared with amounts released at the growth oxygen level. In contrast, cultures grown in 20% oxygen released increased amounts of these eicosanoids compared with release at the growth oxygen level. Release of thromboxane B2 was not significantly different during hypoxia between cultures grown at 5% vs. 20% oxygen. In other experiments, cyclooxygenase activity, stimulated arachidonic acid release by calcium ionophore A23187, and uptake of arachidonic acid were no different in cultures grown at 5% vs. 20% oxygen. However, arachidonic acid release during hypoxia was reduced in 5% cultures and increased in 20% cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of MAP kinases in the control of cPLA2 and arachidonic acid release in endothelial cells

2001 ◽  
Vol 156 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Ingibjörg J. Gudmundsdóttir ◽  
Haraldur Halldórsson ◽  
Kristı́n Magnúsdóttir ◽  
Gudmundur Thorgeirsson
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Map Kinases ◽  
Arachidonic Acid Release ◽  
Acid Release
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