Phospholipid Metabolism in Stimulated Human Platelets: CHANGES IN PHOSPHATIDYLINOSITOL, PHOSPHATIDIC ACID, AND LYSOPHOSPHOLIPIDS
TLDR
Information is provided supporting the existence of two preVIOUSLY postulated pathways for LIBERATION of arachidonate derived from PI and a phospholipase A(2) acting primarily on diacyl ethanolamine phosphoglyceride.Abstract:
Endogenous phospholipid metabolism in stimulated human platelets was studied by phosphorus assay of major and minor components following separation by two-dimensional thin-layer chromatography. This procedure obviated the use of radioactive labels. Extensive changes were found in quantities of phosphatidylinositol (PI) and phosphatidic acid (PA) as a consequence of thrombin or collagen stimulation. Thrombin addition was followed by rapid alterations in the amount of endogenous PI and PA. The decrease in PI was not precisely reciprocated by an increase in PA when thrombin was the stimulus. This apparent discrepancy could be explained by removal of a transient intermediate in PI metabolism, such as diglyceride, formed by PI-specific phospholipase C (Rittenhouse-Simmons, S., J. Clin. Invest.63: 580-587, 1979). Diglyceride would be unavailable for PA formation by diglyceride kinase, if hydrolyzed by diglyceride lipase (Bell, R. L., D. A. Kennerly, N. Stanford, and P. W. Majerus. Proc. Natl. Acad. Sci. U. S. A.76: 3238-3241, 1979) to yield arachidonate for prostaglandin endoperoxide formation. Thrombin-treated platelets also accumulated lysophospho-glycerides. Specifically, lysophosphatidyl ethanolamines accumulated within 15s following thrombin addition. Fatty acid and aldehyde analysis indicated phospholipase A2 activity, with an apparent preference for diacyl ethanolamine phosphoglycerides. In the case of collagen, these changes occurred concomitantly with aggregation and consumption of oxygen for prostaglandin endoperoxide formation.
These studies of endogenous phospholipid metabolism provide information supporting the existence of two previously postulated pathways for liberation of arachidonic acid from platelet phospholipids: (a) the combined action of PI-specific phospholipase C plus diglyceride lipase yielding arachidonate derived from PI; and (b) a phospholipase A2 acting primarily on diacyl ethanolamine phosphoglyceride.read more
Citations
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How is the level of free arachidonic acid controlled in mammalian cells
TL;DR: In order to move forward both conceptually and experimentally it is necessary to take a critical look at the complexities and problems associated with studying arachidonate liberation.
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Changes in membrane phospholipid distribution during platelet activation
TL;DR: It is concluded that the altered orientation of the phospholipids in the plasma membrane of platelets activated by collagen plus thrombin, by diamide, or by calcium ionophore, is the result of a transbilayer movement.
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Diacylglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets
TL;DR: It is shown here that the exogenous diacylglycerol 1-oleoyl-2-acetyl- glycerol (OAG) and TPA evoke similar secretion and aggregation without elevating [Ca2+]i above the basal level of 0.1 µM.
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p38 Mitogen-activated Protein Kinase Phosphorylates Cytosolic Phospholipase A2 (cPLA2) in Thrombin-stimulated Platelets: EVIDENCE THAT PROLINE-DIRECTED PHOSPHORYLATION IS NOT REQUIRED FOR MOBILIZATION OF ARACHIDONIC ACID BY cPLA2*
Ruth M. Kramer,Edda F. Roberts,Suzane L. Um,Angelika G. Börsch-Haubold,Steve P. Watson,Matthew J. Fisher,Joseph A. Jakubowski +6 more
TL;DR: It is found that prevention of proline-directed phosphorylation of cPLA2 in stimulated platelets did not attenuate its ability to release arachidonic acid from platelet phospholipids and the role of p38 kinase is concluded.
References
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Stimulation of phosphatidic acid production in platelets precedes the formation of arachidonate and parallels the release of serotonin.
TL;DR: Phosphatidate production reflects the generation of diacylglycerol by C-type phospholipase degradation of phosphatidylinositol, and may participate in the membrane modification related to the early changes in platelet shape, release reactions or aggregation which occur on stimulation.
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Action of highly purified phospholipases on blood platelets. Evidence for an asymmetric distribution of phospholipids in the surface membrane.
TL;DR: Investigating the action of seven purified phospholipases on intact platelets (both from human and pig) has revealed that membraneospholipids are available to enzymatic breakdown only if the phospholIPase can produce degradation in monolayers spread at an initial surface pressure of at least 34 dynes/cm.
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