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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of hypoxia on the incorporation of [14C]serine into serine glycerophospholipids was investigated in rat brain cortex. Brain slices were incubated, in the presence of the labeled precursor, in Krebs-Henseleit Ringer bicarbonate or Krebs Ringer phosphate, and hypoxia was induced by bubbling nitrogen in the medium. The lowering of oxygen caused an increase of the incorporation of the base into phosphatidylserine in slices incubated in both media, although the effect was greater in Krebs Ringer phosphate. Such an effect was also observed in the homogenate subjected to N2-treatment, with an increase in the incorporation similar to that obtained in slices incubated in Krebs-Henseleit Ringer bicarbonate. Phosphatidylserine is synthesized in mammalian tissues by a "base-exchange" enzyme, strictly Ca2+ dependent, and, moreover, is necessary for protein kinase C activity. We postulate that the increased synthesis of phosphatidylserine might affect signal transduction mechanisms and participate in the modification of lipid metabolism observed in hypoxia and/or ischemia.
Mol Chem Neuropathol 1992 Dec
PMID:Serine incorporation into phosphatidylserine in hypoxic rat brain cortex. 149 81

Phosphatidylserine was found to significantly enhance the binding of phospholipid vesicles to RAW264 macrophages. We have measured the kinetics of non-specific uptake of unilamellar vesicles as a function of phosphatidylserine concentration in these model target membranes. Dimyristoylphosphatidylcholine was the principle component of these phospholipid vesicles. In most experiments, radiolabeled phospholipid and 1 mol% each of both a fluorescent phospholipid and a hapten-containing lipid headgroup were utilized. In the presence of specific anti-hapten antibody phosphatidylserine-containing vesicles are rapidly taken up via phagocytosis. The antibody-independent non-specific uptake of phosphatidylserine-free vesicles was low, as previously reported. However, the presence of 5 mol% phosphatidylserine dramatically enhanced the uptake of phospholipid vesicles by macrophages. This uptake was shown to be principally due to binding to the macrophage surface. Incubation of macrophages in the presence of sodium azide or at 4 degrees C, conditions which are known to inhibit phagocytosis, do not influence the uptake of the lipid vesicles. Fluorescence video-intensification microscopy was used to observe the interaction of carboxyfluorescein-loaded vesicles with macrophages. Fluorescence could not be observed when using phosphatidylserine-free vesicles. However, phosphatidylserine-containing vesicles can be observed bound to the cell periphery. Intracellular fluorescence could not be observed. The binding of phosphatidylserine-containing vesicles was enhanced roughly four-fold over phosphatidylserine because the effect could not be observed with membranes containing 1 mol% or 2.5 mol % phosphatidylserine. In addition, the binding enhancement required the presence of divalent cations in the incubation medium.
Mol Cell Biochem 1984 Sep
PMID:Enhanced binding of phosphatidylserine-containing lipid vesicle targets to RAW264 macrophages. 649 24

Aqueous dispersions of 4 out of 9 phospholipids added individually to the mitochondrial fraction from rat adipocytes altered the activity of pyruvate dehydrogenase in a dose-dependent manner from 1 to 300 microM. Phosphatidylserine increased and phosphatidylcholine, phosphatidylinositol and phosphatidylinositol-4-phosphate decreased enzyme activity. The stimulation of pyruvate dehydrogenase induced by phosphatidylserine may be reversed to below basal activity by phosphatidylinositol-4-phosphate and to basal activity by NaF, a pyruvate dehydrogenase phosphatase inhibitor. The inhibition of pyruvate dehydrogenase induced by phosphatidylinositol-4-phosphate may be restored to basal levels by the addition of calcium. These results suggest that phosphatidylserine activates pyruvate dehydrogenase activity through activation of the phosphatase, perhaps forming a phosphatidylserine-calcium complex. The inhibition by phosphatidylinositol-4-phosphate may be mediated by disruption of the enzyme complex. The phospholipids may play a physiological role in the regulation of pyruvate dehydrogenase activity.
Mol Cell Biochem 1983
PMID:Phospholipids and the regulation of pyruvate dehydrogenase from rat adipocyte mitochondria. 664 16

Phosphatidylserine (PS) synthesis was studied in glioma C6 cells with [14C]serine and in the presence or absence of the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA). It was found that incubation of the cells with 10 nM or 100 nM TPA for 1 h inhibited PS formation by 30% and 60%, respectively. Long-term (18 h) treatment of the cells with 100 nM TPA diminished PS formation and further addition of TPA to down-regulated cells did not affect PS synthesis. The data show that the changes in PS synthesis can be associated with alterations in morphology of cell and the actin cytoskeleton organization. The role of protein kinase C in this process is discussed.
Biochem Mol Biol Int 1995 Jul
PMID:Phosphatidylserine synthesis in phorbol ester treated glioma C6 cells. 754 66

Diffusion of the fluorescent membrane probe, Dil-C16 (3), from labelled to unlabelled human erythrocytes has been employed to monitor hemi-fusion (membrane fusion) in monolayers of cells exposed to poly(ethylene glycol) (PEG). Diffusion of the cytoplasmic probe, 6-carboxyfluorescein, was used similarly to monitor cell fusion (cytoplasmic mixing). Hemi-fusion, which is normally seen when erythrocytes are exposed to dehydrating concentrations of commercial PEG 6000, did not occur when the PEG was pretreated with Chelex 100 resin to remove metal ions. Cytoplasmic mixing, which is normally observed when the dehydrated erythrocytes are substantially rehydrated, also failed to occur when both PEG 6000 and the rehydrating buffer had been treated with Chelex 100. The re-addition to Chelex-treated PEG of components removed by the resin, and the addition of 10 mu mM concentrations of La3+ or Al3+, restored its ability to induce hemi-fusion and cell fusion. Higher concentrations of several other metals, including Ca2+, were also effective. These observations show that metal ions are required for hemi-fusion with erythrocytes in the presence of PEG, and that dehydration alone is insufficient to induce hemi-fusion. Phosphatidylserine was apparently not accessible in erythrocytes treated with PEG 6000 until the cells were rehydrated. This indicates that metal ions do not assist the hemi-fusion of erythrocytes by forming trans complexes with surface phosphatidylserine when the cells are dehydrated by PEG.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Membr Biol
PMID:Interactions between metal ions and poly(ethylene glycol) in the fusion of human erythrocytes. 774 82

Phosphatidylserine, which is necessary for protein kinase C activity, is synthesized in mammalian tissues by the Ca(2+)-dependent base exchange enzyme. The synthesis of phosphatidylserine is greater in slices or homogenates of rat cerebral cortex subjected to hypoxia by N2 treatment when compared with O2 plus 5% CO2. An intermediate effect was observed when the treatment was done with N2 plus 5% CO2. Incorporation rates were dependent on Ca2+ in Krebs-Henseleit Ringer bicarbonate medium, being greater with 2 mM Ca2+ than with the same medium prepared without Ca2+. The increase of phosphatidylserine synthesis, due to hypoxia, was, on the contrary, more evident in the medium lacking added Ca2+. Similar results were obtained with the homogenates. This suggests that elevation of intracellular Ca2+, caused by hypocapnia and hypoxia, may be responsible for the greater incorporation of serine into phosphatidylserine. In both cerebrocortical slices and homogenate, [14C]serine incorporation decreased with development both in O2 plus 5% CO2 and N2-treated preparations. However, in younger rats (14-18 days) hypoxia induced a lesser increase of phosphatidylserine than in 40 day old animals. We suggest that a regulatory mechanism for phosphatidylserine synthesis is established during development and that N2-treatment can increase phosphatidylserine synthesis by interfering with this regulatory mechanism.
Mol Cell Biochem 1993 Sep 22
PMID:Phosphatidylserine synthesis in rat cerebral cortex: effects of hypoxia, hypocapnia and development. 830 87

The effects of differences in the fatty acid composition of the lipids of egg yolk on the subsequent levels of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) in the total phospholipids and in the isolated phospholipid classes of the embryonic brain were investigated by a comparison of two domesticated avain species, the chicken and the duck. The yolk phospholipids of chicken eggs contained similar proportions of 20:4n-6 and 22:6n-3 (approx. 6% wt/wt of total fatty acids). In marked contrast, the yolk phospholipids of commercially produced duck eggs contained an overwhelming preponderance of 20:4n-6 over 22:6n-3 (approx. 10% cf.1%). These differences between the yolks of the two species were only partly reflected in the fatty acid compositions of the total phospholipids of the embryonic brains at equivalent developmental stages. Typically, the chicken brain phospholipids contained approximate proportions of 20:4n-6 and 22:6n-3 of 8% and 17%, respectively, whereas both these polyunsaturates were present at approx. 11% in the duck samples. The brain phospholipids were resolved into their component phospholipid classes by high performance liquid chromatography. In both species, phosphatidylcholine contained only low levels of 20:4n-6 and 22:6n-3, whereas phosphatidylethanolamine displayed a high content of 22:6n-3. Phosphatidylserine was also rich in 22:6n-3 whereas phosphatidylinositol exhibited a high proportion of 20:4n-6. The results suggest that the relatively low level of 22:6n-3 in the yolk of duck eggs is partly compensated for by an enhanced efficiency in the incorporation of this fatty acid into the brain phospholipids, in comparison with the chicken.
Comp Biochem Physiol B Biochem Mol Biol 1996 Oct
PMID:The fatty acid composition of brain phospholipids from chicken and duck embryos. 893 95

The phospholipid-dependent protein kinase C is implicated in the regulation of cellular motility and energy metabolism. Phosphatidylserine, a main cofactor of protein kinase C, is involved in the regulation of glyceraldhehyde-3-phosphate dehydrogenase, which as actin, was shown to be phosphorylated by purified protein kinase C. Here, we study the effect of phosphatidylserine on the enzyme-substrate interaction of protein kinase C with glyceraldhehyde-3-phosphate dehydrogenase and actin. The stoichiometry of glyceraldhehyde-3-phosphate dehydrogenase phosphorylation is not affected by varying the level of phosphatidylserine. However, actin phosphorylation is dependent on phosphatidylserine level, peaking at high phosphatidylserine concentration. Moreover, if actin and glyceraldhehyde-3-phosphate dehydrogenase are cophosphorylated at high phosphatidylserine concentration, actin phosphorylation is favored, despite lower affinity for protein kinase C. Hence, phosphatidylserine directs differential phosphorylation of these key proteins of glycolysis and cellular motility and might be capable of recruiting protein kinase C for preferential actin phosphorylation. The sedimentation of phosphorylated actin is increased 3.8 fold and total actin 1.7 fold, suggesting that phosphorylation promotes actin polymerization.
Biochem Mol Biol Int 1996 Dec
PMID:Phosphatidylserine directs differential phosphorylation of actin and glyceraldehyde-3-phosphate dehydrogenase by protein kinase C: possible implications for regulation of actin polymerization. 898 31

Transduction of extracellular signals through the membrane involves both the lipid and protein moiety. Phosphatidylserine participates to these processes as a cofactor for protein kinase C activity and thus the existence of a regulatory mechanism for its synthesis ought to be expected. In plasma membranes from rat cerebral cortex, the activity of serine base exchange enzyme, that is mainly responsible for phosphatidylserine synthesis in mammalian tissues, was reduced by the addition to the incubation mixture of AlF4- or GTP-gamma-S, known activators of G proteins, whereas ATP was almost uneffective. GTP-gamma-S inhibited the enzyme activity only at relatively high concentration (> 0.5 mM). When the synthesis of phosphatidylserine in the same cerebral area was investigated by measuring the incorporation of labelled serine into the phospholipid in the homogenate buffered at pH 7.6, ATP had an inhibitory effect as GTP-gamma-S and AlF4-. Heparin activated both serine base exchange enzyme in plasma membranes and phosphatidylserine synthesis in the homogenate. The preincubation of plasma membranes in the buffer without any other addition at 37 degrees C for 15 min reduced by 30% serine base exchange enzyme activity. The remaining activity responded to the addition of GTP-gamma-S but was insensitive to 5 mM AlF-4, a concentration that inhibited by 60% the enzyme assayed without preincubation. These results indicate the existence of different regulatory mechanisms, involving ATP and G proteins, possibly acting on different enzymes responsible for the synthesis of phosphatidylserine. Since previous studies have shown that hypoxia increases the synthesis of this phospholipid in brain slices or homogenate (Mozzi et al. Mol Cell Biochem 126: 101-107, 1993), it is possible that hypoxia may interfere with at least one of these mechanisms. This hypothesis is supported by the observation that in hypoxic homogenate 20 mM AlF-4 was not able to reduce the synthesis of phosphatidylserine as in normoxic samples. A similar difference between oxygenated and hypoxic samples, concerning their response to AlF4-, was observed when the incorporation of ethanolamine into phosphatidylethanolamine was studied. The incorporation of choline into phosphatidilcholine was, on the contrary, inhibited at a similar extent in both experimental conditions.
Mol Cell Biochem 1997 Mar
PMID:Different mechanisms regulate phosphatidylserine synthesis in rat cerebral cortex. 906 92

In rat thymic lymphocytes, accumulation of phosphatidic acid (PA) occurs at the same time as decrease in cAMP levels and activation of a cAMP-specific phosphodiesterase (PDE) [type 4, EC 3.1.4.17 (PDE4)]. We investigated the nature of the PDE activated by PA and the mechanism of activation by using recombinant cAMP-specific PDE4 isoforms derived from three different genes (PDE4A, PDE4B, and PDE4D). The "long" variants expressed from each gene (PDE4A5, PDE4B1, and PDE4D3) were activated by PA, whereas the "short" variants (PDE4A1, PDE4B2, PDE4D1, and PDE4D2) were not. Phosphatidylserine was an activator that was as effective as PA, whereas phosphatidylcholine was ineffective, indicating that activation was restricted to anionic phospholipids. PA caused an increase in the Vmax value of PDE4D3 without affecting the Km value of the enzyme for the cAMP substrate. PA also caused a change in the Mg2+ requirement for hydrolysis. Half-maximal stimulation of the PDE was obtained with approximately 10 microg/ml PA. Although protein kinase A-mediated phosphorylation of PDE4D3 produces effects similar to those elicited by PA, the mechanism of PA-induced activation was not found to involve a phosphorylation. Instead, several observations suggest that PA may directly interact with the enzyme. The stimulation of cAMP PDEs by PA and other acidic phospholipids may be a mechanism by which growth factors and hormones modulate the cAMP-dependent signal transduction pathway during cell stimulation.
Mol Pharmacol 1997 Feb
PMID:Selective activation of rolipram-sensitive, cAMP-specific phosphodiesterase isoforms by phosphatidic acid. 920 29


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