Cyclic AMP metabolism in cholesterol-rich platelets.
25 May 1977-Journal of Biological Chemistry (American Society for Biochemistry and Molecular Biology)-Vol. 252, Iss: 10, pp 3310-3314
TL;DR: It is demonstrated that incorporation of cholesterol into platelet membranes is associated with a diminished inhibitory effect of prostaglandin E, on platelet aggregation and therefore adenosine 3’:5’-monophosphate production in these platelets.
About: This article is published in Journal of Biological Chemistry.The article was published on 1977-05-25 and is currently open access. It has received 125 citations till now. The article focuses on the topics: Platelet.
Citations
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TL;DR: Membrane fatty acid composition, phospholipid composition, and cholesterol content can be modified in many different kinds of intact mammalian cells, and many of the functional responses probably are caused directly by the membrane lipid structural changes, which affect either bulk lipid fluidity or specific lipid domains.
1,437 citations
TL;DR: Two images of the cell membrane are presented — as a sea of lipid with islands of protein and as a matrix of protein with lakes of lipid, both of which suggest that zones of fluid lipid within the membrane form the environment for membrane proteins.
Abstract: Early in this century, colloid chemists debated about whether cells were bounded by a surface membrane. Today, they debate about the organization of molecules within that membrane. The research involved has led to two images of the cell membrane — as a sea of lipid with islands of protein and as a matrix of protein with lakes of lipid. Both concepts suggest that zones of fluid lipid within the membrane form the environment for membrane proteins. Much of this lipid is in the form of a bilamellar leaflet with hydrophilic portions that face the aqueous environment on either side and . . .
413 citations
315 citations
TL;DR: Although active Na-K transport is not influenced by cholesterol enrichment of human red cells, several carrier-mediated transport pathways are inhibited and the cotransport of Na + K and similar results have been obtained by others in studies of organic acid transport and the transport of small neutral molecules such as erythritol and glycerol.
Abstract: Cholesterol and phospholipid are the two major lipids of the red cell membrane. Cholesterol is insoluble in water but is solubilized by phospholipids both in membranes and in plasma lipoproteins. Morever, cholesterol exchanges between membranes and lipoproteins. An equilibrium partition is established based on the amount of cholesterol relative to phospholipid (C/PL) in these two compartments. Increases in the C/PL of red cell membranes have been studied under three conditions: First, spontaneous increases in vivo have been observed in the spur red cells of patients with severe liver disease; second, similar red cell changes in vivo have been induced by the administration of cholesterol-enriched diets to rodents and dogs; third, increases in membrane cholesterol have been induced in vitro by enriching the C/PL of the lipoprotein environment with cholesterol-phospholipid dispersions (liposomes) having a C/PL of greater than 1.0. In each case, there is a close relationship between the C/PL of the plasma environment and the C/PL of the red cell membrane. In vivo, the C/PL mole ratio of red cell membranes ranges from a normal value of 0.09--1.0 to values which approach but do not reach 2.0. In vitro, this ratio approaches 3.0. Cholesterol enrichment of red cell membranes directly influences membrane lipid fluidity, as assessed by the rotational diffusion of hydrophobic fluorescent probes such as diphenyl hexatriene (DPH). A close correlation exists between increases in red cell membrane C/PL and decreases in membrane fluidity over the range of membrane C/PL from 1.0 to 2.0; however, little further change in fluidity occurs when membrane C/PL is increased to 2.0--3.0. Cholesterol enrichment of red cell membranes is associated with the transformation of cell contour to one which is redundant and folded, and this is associated with a decrease in red cell filterability in vitro. Circulation in vivo in the presence of the spleen further modifies cell shape to a spiny, irregular (spur) form, and the survival of cholesterol-rich red cells is decreased in the presence of the spleen. Although active Na-K transport is not influenced by cholesterol enrichment of human red cells, several carrier-mediated transport pathways are inhibited. We have demonstrated this effect for the cotransport of Na + K and similar results have been obtained by others in studies of organic acid transport and the transport of small neutral molecules such as erythritol and glycerol. Thus, red cell membrane C/PL is sensitive to the C/PL of the plasma environment. Increasing membrane C/PL causes a decrease in membrane fluidity, and these changes are associated with a reduction in membrane permeability, a distortion of cell contour and filterability and a shortening of the survival of red cells in vivo.
280 citations
TL;DR: It is demonstrated that secreted APP processing derivatives and Aβ can be modulated in the brain of an animal by diet and evidence that cholesterol plays a role in the modulation of APP processing in vivo is provided.
261 citations
References
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Journal Article•
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
289,852 citations
TL;DR: A simple and sensitive assay for adenosine 3':5'-cyclic monophosphate (cAMP) has been developed that is based on competition for protein binding of the nucleotide, presumably to a cAMP-dependent protein kinase.
Abstract: A simple and sensitive assay for adenosine 3′:5′-cyclic monophosphate (cAMP) has been developed that is based on competition for protein binding of the nucleotide, presumably to a cAMP-dependent protein kinase. The nucleotide-protein complex is adsorbed on a cellulose ester filter. Assay conditions are such that a binding constant approaching 10-9 M is obtained, and the assay is thus sensitive to 0.05-0.10 pmol of cAMP.
3,048 citations
TL;DR: The almost exclusive transformation of the endoperoxide structure into non-prostaglandin derivatives supports the hypothesis that the end operoxides can participate directly and not by way of the classical prostaglandins in regulation of cell functions.
Abstract: Arachidonic acid incubated with human platelets was converted into three compounds, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid, 12L-hydroxy-5,8,10-heptadecatrienoic acid, and the hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid. The formation of the two latter compounds from arachidonic acid proceeded by pathways involving the enzyme, fatty acid cyclo-oxygenase, in the initial step and with the prostaglandin endoperoxide, PGG2, as an intermediate. The first mentioned compound was formed from 12L-hydroperoxy-5,8,10,14-eicosatetraenoic acid, which in turn was formed from arachidonic acid by the action of a novel lipoxygenase. Aspirin and indomethacin inhibited the fatty acid cyclo-oxygenase but not the lipoxygenase, whereas 5,8,11,14-eicosatetraynoic acid inhibited both enzymes. The almost exclusive transformation of the endoperoxide structure into non-prostaglandin derivatives supports the hypothesis that the endoperoxides can participate directly and not by way of the classical prostaglandins in regulation of cell functions. The observed transformations of arachidonic acid in platelets also explain the aggregating effect of this acid.
1,323 citations
TL;DR: A fluorescence polarization technique with 1,6-diphenyl 1,3,5-hexatriene as a probe was employed to determine the microviscosity, n, in liposomes and biological membranes of different cholesterol to phospholipid mol ratio and the degree of rotational mobility of concanavalin A receptor sites in cell membranes was determined.
681 citations
TL;DR: Some recent advances in understanding of the molecular dynamics of lipids in both natural and model membrane systems, which have been obtained using the techniques of differential scanning calorimetry, nuclear magnetic resonance, electron spin resonance, X-ray diffraction, infra-red and Raman spectroscopy are summarized.
509 citations