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Biomedical subjects

M F Simon

Publications and source records attributed to M F Simon.

41 records · Page 3Linked to original sources

Studies on topological distribution of arachidonic acid replacement in platelet phospholipids and on enzymes involved in the phospholipid effect accompanying platelet activation.

In this short review recent results obtained on platelet phospholipid metabolism are summarized. The first part reports a topological study of arachidonic acid (AA) replacement in platelet phospholipids. It is shown that incubation of platelets with radioactive free arachidonic acid leads to a labelling of the phospholipids present inside the platelet, whereas the exchange of intact phosphatidylcholine (PC) molecules with the plasma lipoproteins occurs on the platelet outer surface. This should allow a selective labelling of the small external pool of AA in order to follow its behaviour during platelet activation. In the second part, some enzymes involved in the metabolism of phosphatidylinositol (PI) have been further characterized. The first one is a diglyceride-lipase, which is located in the plasma membrane and releases the two fatty acids esterifying the diglycerides formed from PI by the action of the platelet phospholipase C. Such an enzyme is probably responsible for the release of AA from PI occurring upon platelet activation. On the other hand, cytosolic phospholipid exchange proteins able to catalyse the transfer of PI between membranes have been identified. The possible role of the enzymes involved in the acceleration of PI turnover occurring during platelet activation is discussed.

Arachidonic Acid↗

Phosphatidic and lysophosphatidic acid production in phospholipase C-and thrombin-treated platelets. Possible involvement of a platelet lipase.

Incubation of 32P-labelled platelets with Clostridium welchii phospholipase C greatly stimulates 32P-incorporation into phosphatidic and lysophosphatidic acids. A net synthesis is demonstrated for both phospholipids, which exhibit identical specific radioactivities. Phosphatidic acid production roughly parallels the phospholipase C-induced aggregation, whereas lysophosphatidic acid appears secondarily during cell lysis. The same qualitative variations are observed during thrombin-induced aggregation. At the physiological pH used throughout the incubations, platelets display no phospholipase A activity towards phosphatidic acid, whereas diglycerides are deacylated by platelet lysates. On the basis of these findings, a mechanism for phosphatidic and lysophosphatidic acid production is proposed, involving a phosphorylation of the di- and monoglycerides formed upon phospholipase C and lipase action. The possible role of such a pathway in regulating arachidonic acid release from phospholipids during platelet activation is discussed.

Animals↗