Abstract
Human umbilical vein endothelial cells (HUVEC) in culture synthesize prostacyclin (PGI 2) as the predominant metabolite of arachidonic acid which is derived from the deacylation of phospholipids. Under basal-unstimulated condition, PGI 2 release from HUVEC is extremely low; however, when endothelial monolayers were preincubated with the natural vitamin E ( R, R, R- α-tocopherol), we found a dose-dependent potentiation of basal PGI 2 release. When HUVEC were stimulated with arachidonate or ionophore A23187, there was a dose-dependent increase of PGI 2 release in response to tocopherol enrichment. When HUVEC were labelled with [ Me- 3H]choline followed by A23187 stimulation, a significantly higher lysophosphatidylcholine was found in the tocopherol-enriched cells, suggesting a change in enzymes involved in phosphatidylcholine metabolism. Analysis of these enzymes revealed that phospholipase A 2 activity was enhanced by tocopherol enrichment, whereas lysophospholipase and acyl-CoA acyltransferase were unaffected. To determine the specificity of the tocopherol molecule, different analogues were tested for their PGI 2 potentiating activity. Results showed that the free hydroxyl group on the chromanol ring as well as the phytyl side-chain are absolutely required to stimulate PGI 2 release, whereas, different methyl locations and substituents on the chromanol ring had no effect. These studies demonstrated that tocopherol potentiates basal PGI 2 release in HUVEC and in contrast to its reported inhibitory role in rat platelets, myocadium and neutrophils, tocopherol stimulates phospholipase activity in HUVEC.
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