Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:22276-27-3 (hexadecyl)
 2,701 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently demonstrated that arachidonate [20:4(5,8,11,14)] was primarily linked to the hexadecyl (16:0) and octadecenyl (18:1) species of alkylacyl derivatives of glycerolphosphocholine (GroPCho). Consistent with the involvement of arachidonate-specific CoA-independent transacylase in the synthesis of platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-GroPCho), 16:0 and 18:1 PAF species were formed upon antigen stimulation [Joly, F., Breton, M., Wolf, C., Ninio, E. & Colard, O. (1992) Biochim. Biophys. Acta 1125, 305-312]. In the present work, addition of lyso-PAF to mast cells resulted in PAF production. We analyzed the PAF species formed in the presence of a defined lyso-PAF molecular species in order to differentiate between either direct acetylation or involvement of the membrane precursor. The 18:1 lyso-PAF was more effective than the 16:0 in producing PAF which was composed of 95% 18:1 PAF, the balance being 16:0, indicating that part of the acetylated lyso-PAF originated from the cellular pool of alkyl-arachidonyl-GroPCho in resting cells. Consistent with alkyl-arachidonyl-GroPCho species content and acetyltransferase specificity, similar amounts of 16:0 and 18:1 PAF species were formed when mast cells were stimulated with antigen. Supplemented with 16:0 or 18:1 lyso-PAF, antigen-stimulated mast cells responded by 230% and 125% increase in PAF synthesis, respectively. As expected, the amount of the PAF species corresponding to the added lyso-PAF was increased. More interestingly, addition of 16:0 lyso-PAF almost doubled the amount of 18:1 PAF content as compared to antigen alone, thus indicating that the lyso-PAF formed via the CoA-independent transacylase was significantly used for PAF synthesis, despite a large excess of exogenous lyso-PAF. The CoA-independent transacylase, measured using [3H]lyso-PAF as a substrate in sonicates from antigen-stimulated cells, was decreased concurrently with PAF formation. In conclusion, we show that when lyso-PAF is added to mast cells, a direct acetylation may occur. However, PAF is preferentially synthesized through a mechanism involving the CoA-independent transacylase reaction.
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PMID:Biosynthesis of platelet-activating factor in cultured mast cells. Involvement of the CoA-independent transacylase demonstrated by analysis of the molecular species of platelet-activating factor. 840 3

The effect of platelet-activating factor (1-O-hexadecyl-2-acetyl-sn- glycero-3-phosphocholine, PAF) and two related molecules, 1-O-hexadecyl-sn-glycero-3-phosphocholine (LPAF) and 1-palmitoyl-sn-glycero-3- phosphocholine (LPC) on dielaidoylphosphatidylethanolamine (DEPE) lipid structure and polymorphism has been studied by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) and 31P nuclear magnetic resonance (31P-NMR) spectroscopies. From the interaction of these molecules with DEPE it is concluded that all of them stabilize the lamellar phase with respect to the hexagonal HII phase and this effect is clear even at concentrations of these compounds as low as 1 mol%. It is also shown that, although they perturb the gel to liquid-crystalline phase transition of DEPE up to a similar extent, fluidizing the membrane, PAF but not LPAF or LPC, induces the presence of more than one peak in the calorimetric profile. Moreover, FTIR data indicate that lateral phase separations formed by PAF-rich phases are taking place. Remarkably, delta H of the main transition decreases at concentrations lower than 2 mol% but remains nearly constant up to 30 mol%. 31P-NMR measurements showed that all these molecules were capable of inducing isotropic signals in the spectra produced by molecules associated to membranes before micellization of the vesicles.
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PMID:Effects of platelet-activating factor and related lipids on dielaidoylphosphatidylethanolamine by DSC, FTIR and NMR. 843 61

Significant changes in platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) concentration have been observed in rabbit endometrium during the preimplantation period, but, under in vitro conditions, constitutive PAF biosynthesis by isolated endometrial tissues was not easily demonstrable. Relative changes in enzymes involved in the synthesis and metabolism of PAF in the tissues may account for this disparity. In addition, during this period of preimplantation, marked changes in PAF receptor concentration have been noted. The present study examines the factors that may modulate the metabolism of exogenous [3H]PAF in the endometrium of rabbits on day 6 of pregnancy. Since preferential [3H]PAF binding in situ by the glandular epithelial, but not by the stromal, cells was demonstrated, their cell-specific metabolism of exogenous [3H]PAF was also examined. After entry into the endometrial cell, [3H]PAF was rapidly metabolized by the sequential action of cytosolic Ca(2+)-independent acetylhydrolase to [3H]lyso-PAF and this was in turn acylated by membrane-associated transacylase to [3H]alkylacyl-glycerylphosphorylcholine. PAF resynthesis was not observed and, in stromal cells, there was a significant build-up of [3H]lyso-PAF, suggesting that lyso-PAF:acetyl-CoA acetyl-transferase may be a limiting factor. In the glandular epithelial cells, however, there was a significant accumulation of a neutral lipid without a significant build-up of [3H]lyso-PAF or [3H]PAF. The neutral lipid co-migrated with the product of phospholipase C-catalysed metabolism of PAF and authentic 1-O-hexadecyl-2-acetyl-glycerol. In addition, the elution times of phospholipase C digestion of C18 PAF and the neutral lipid produced by cellular metabolism of [3H]PAF, determined by gas chromatography/flame ionization detection, were similar. It seems that it is the synthesis of the neutral lipid from reacetylated [3H]lyso-PAF that prevented [3H]PAF accumulation under in vitro conditions. This is the first documentation of the synthesis of this lipid in the mammalian uterus. The lipid may serve as the precursor for de novo PAF synthesis in the glandular epithelial cells during endometrial proliferation.
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PMID:Differential metabolism of exogenous platelet-activating factor by glandular epithelial and stromal cells of rabbit endometrium. 856 77

Monocyte-derived macrophages and macrophage-derived foam cells in arterial tissue may undergo phagocytic activation and thereby contribute to an inflammatory reaction. We have investigated the effect of phagocytic activation on the formation of platelet-activating factor (1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF-acether, PAF), a proinflammatory phospholipid, in human monocyte-derived macrophages (macrophages) and in cholesterol-loaded macrophage foam cells (foam cells). Adherent human monocyte-derived macrophages were transformed into foam cells upon incubation with acetylated low-density lipoproteins (Ac-LDL). Such foam cells characteristically displayed a markedly increased content of cholesteryl esters compared with macrophages (4.3 +/- 1.3 microgram/microgram DNA and 0.2 +/- 0.3 microgram/microgram DNA, n = 5, respectively). After phagocytic stimulation with serum-opsonized zymosan (OPZ), both macrophages and foam cells synthesized PAF transiently with maximal production (0.5-1.1 pmol PAF/microgram DNA, n = 5, corresponding to 4.0-8.8 pmol PAF/10(6) cells, as assessed by bioassay) occurring approximately 15 min after stimulation. A major fraction of the synthesized PAF remained cell-associated; such PAF was composed mainly of the hexadecyl (16:0 PAF, approximately 75%) and the octadecenyl (18:1 PAF) species and of trace amounts of octadecyl (18:0 PAF), as assessed by reverse-phase liquid chromatography. Addition of exogenous 16:0 lyso-PAF alone triggered PAF formation (0.9-1.7 pmol PAF/microgram DNA, after 15 min of cellular stimulation); simultaneous cellular stimulation with OPZ and 16:0 lyso-PAF increased PAF formation in an additive manner. Acetyltransferase, the enzyme which acetylates the precursor lyso-PAF and transforms it into PAF, displayed elevated activity both in macrophages and in foam cells, attaining 83-240 pmol PAF formed per min per mg DNA (n = 4); such elevated activity was not increased by OPZ-stimulation. The activity of acetylhydrolase, the PAF-degrading enzyme, was similar in macrophages and in foam cells, and varied between 120 pmol and 320 pmol PAF degraded per min per mg DNA (n = 5). Cell-associated acetylhydrolase activity was increased significantly by 40+/-15 % (P < 0.003, n = 5) after 15 - 30 min of activation with OPZ compared with non-stimulated cells and may account for the rapid decrease in cellular PAF content observed approximately 30 min after stimulation. These studies have established that metabolism of PAF in foam cells closely resembles that in macrophages, and thus PAF metabolism is largely independent of cellular cholesterol content. Moreover our data are consistent with the hypothesis that both macrophages and macrophage-derived foam cells upon phagocytic-activation constitute a significant transient source of PAF at inflammatory sites in the arterial intima where this phospholipidic mediator may exert potent proatherogenic and prothrombotic effects.
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PMID:Phagocytic activation induces formation of platelet-activating factor in human monocyte-derived macrophages and in macrophage-derived foam cells. Relevance to the inflammatory reaction in atherogenesis. 861 85

The goal of the current study was to examine the formation of phospholipids, 1-radyl-2-lysosn-glycero-phospholipids (lyso-PL) and 2-acetylated phospholipids (such as PAF) as well as mechanisms responsible for generating these phospholipids in bronchoalveolar lavage fluid (BAI.F) from allergic subjects challenged with antigen. Bronchoalveolar lavage was performed in normal and allergic subjects before, 5-30 min, 6 h, and 20 h after segmental antigen challenge via a wedged bronchoscope. Levels of 1-hexadecyl-2-lyso-phospholipids and 1-hexadecyl-2-acetyl-phospholipids were initially determined by negative ion chemical ionization gas chromatography/mass spectrometry (NICI-GC/MS). Antigen dramatically elevated quantities of 1-hexadecyl-2-lyso-phospholipids in allergic subjects 20 h after challenge when compared to non-allergic controls. In contrast, there was not a significant increase in levels of 1-hexadecyl-2-acetyl-phospholipids after antigen challenge. Closer examination of 1-radyl-2-lyso-sn-glycero-3-phosphocholine (GPC) revealed that 1-palmitoyl-2-lyso-GPC, 1-myristoyl-2-lyso-GPC and 1-hexadecyl-2-lyso-GPC were three major molecular species produced after antigen challenge. 1-palmitoyl-2-lyso-GPC increased sevenfold to levels of 222 +/- 75 ng/ml of BALF 20 h after antigen challenge. The elevated levels of lyso-PL correlated with levels of albumin used to assess plasma exudation induced by allergen challenge. In contrast, the time course of prostaglandin D2 (PGD2) or 9 alpha, 11 beta PGF2 (11 beta PGF2) formation did not correlate with lyso-PL generation. To examine the mechanism leading to lyso-phospholipid formation in antigen-challenged allergic subjects, secretory phospholipase A2 (PI.A2) and acetyl hydrolase activities were measured. There was a significant increase in PLA2 activity found in BALF of allergic subjects challenged with antigen when compared to saline controls. This activity was neutralized by an antibody directed against low molecular mass, (14 kD) human synovial PLA2 and dithiothreitol. Acetyl hydrolase activity also markedly increased in BALF obtained after antigen challenge. This study indicates that high levels of lyso-PLs are present in airways of allergic subjects challenged with antigen and provides evidence for two distinct mechanisms that could induce lyso-PL formation. Future studies will be necessary to determine the ramifications of these high levels of lyso-phospholipids on airway function.
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PMID:Antigen-induced generation of lyso-phospholipids in human airways. 864 33

It is generally believed that neuronal growth cone collapsing factors are proteins that interact with membrane-bound receptors. Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF) - a phospholipid autocoid, also interacts with a membrane-bound neuronal receptor which is similar in nature to collapsing factor receptors. We report that PAF and the nonhydrolyzable PAF agonist, methyl carbamyl PAF (1-O-hexadecyl-2N-methylcarbamyl-sn-glycero-3-phosphocholine, mc-PAF), evoke a dose-dependent neuronal growth cone collapse. This collapse is specifically attenuated by the PAF receptor antagonist BN-52021. These data point to a PAF receptor-mediated growth cone collapse. Therefore, PAF must be added to the list of collapsing factors which potentially guide axons to their proper targets in the developing nervous system.
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PMID:Platelet-activating factor produces neuronal growth cone collapse. 874 65

The purpose of the present study was to investigate the role of platelet-activating factor (PAF, 1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine), a phospholipid mediator synthesized by endothelial and smooth muscle cells, in the modulation of vascular tone and blood pressure. In pentobarbitone-anaesthetised rabbits, unloading of the carotid sinus baroreceptors by a bilateral carotid artery occlusion elicited a reflex rise in arterial pressure which was markedly potentiated by pretreating the animals with the PAF receptor antagonists WEB 2086 [3-4-(2-chlorphenyl)-9-methyl-6H-thieno-3,2f-1,2,4-triazolo-4, 3 a-1,4-diazepin-2-yl-(4-morpholinyl)-I-propanone; 2, 5 or 10 mg kg-1, i.v.] or BN 52021 (ginkgolide B; 0.1, 0.3 or 1.0 mg kg-1, i.v.). The increases in systemic vascular resistance induced by noradrenaline (30 micrograms kg-1, i.v.) or by the central activation of the sympathetic nervous system with glutamate (1 mg kg-1, intracerebroventricular) were also significantly potentiated in animals pretreated with WEB 2086 (5 mg kg-1, i.v.). In contrast, pretreatment with the cyclooxygenase inhibitor indomethacin (3 mg kg-1, i.v.) did not affect the haemodynamic actions of noradrenaline, thus excluding the possibility that prostacyclin may modulate the potentiating effect. To further confirm that PAF is released during systemic vasoconstriction, the cardiovascular PAF receptors were desensitized by the daily administration of PAF (3 micrograms kg-1, i.v.) for seven days. This procedure significantly reduced the intensity and duration of the hypotensive response to a subsequent PAF injection (3 micrograms kg-1, i.v.). In desensitized animals, the hypertensive response to bilateral carotid artery occlusion was potentiated to the same extent as in the animals treated with PAF receptor antagonists. Inhibition of PAF biosynthesis by pretreatment of the animals with the phospholipase A2 inhibitor mepacrine (5 mg kg-1, i.v.) also enhanced the increase in blood pressure elicited by carotid artery occlusion. We conclude that PAF is involved in the acute but not basal modulation of vasomotor tone and, hence, arterial pressure, probably by a negative feedback mechanism triggered by important increases in the vascular tone.
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PMID:Pharmacological evidence of a role for platelet activating factor as a modulator of vasomotor tone and blood pressure. 885 1

Evidence is accumulating suggesting that platelet-activating factor plays a role in inflammatory dermatoses. Mass spectrometric methods were used to examine the molecular species of sn-2 acetyl glycerophosphocholines (GPC) synthesized by primary cultures of human neonatal foreskin-derived keratinocytes. Ionophore-stimulated keratinocytes synthesize both 1-alkyl and 1-acyl sn-2 acetyl-GPC, and the relative amounts were as follows: hexadecyl > palmitoyl > octadecyl > stearoyl at the sn-1 position. PAF synthesis in the keratinocyte-derived cell line HaCaT was inhibited by dexamethasone, suggesting that the anti-inflammatory effects of glucocorticosteroids in inflammatory dermatoses might be in part related to the inhibition of the synthesis of mediators such as PAF.
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PMID:Identification of sn-2 acetyl glycerophosphocholines in human keratinocytes. 924 3

The purpose of the present study was to investigate the involvement of nitric oxide (NO) in the modulatory role of platelet-activating factor (PAF, 1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine), a vasoactive phospholipid mediator synthesized by endothelial cells, on the vascular tone and arterial blood pressure. In pentobarbitone-anaesthetized rabbits, unloading of the carotid sinus baroreceptors by a bilateral carotid artery occlusion elicited a reflex rise in systemic vascular resistance, which was markedly potentiated by pretreating the animals with the PAF receptor antagonist WEB 2086 ([3-4-(2-chlorphenyl-)-9-methyl-6H-thieno-3,2-f-1,2,4-triazolo-4,3 -alpha-1,4 -diazepin-2-yl-(4-morpholinyl)-1-propanone]; 5 mg/kg, i.v.). In contrast, the inhibition of the biosynthesis of NO via NO synthase using N omega-nitro-L-arginine methyl ester (L-NAME) neither affected the systemic vasoconstriction induced by carotid artery occlusion nor modified the potentiating effect of WEB 2086. The haemodynamic alterations induced by L-NAME administration were corrected by continuous infusions of the directly-acting vasodilators sodium nitroprusside or diazoxide. The results of the present study confirm previous studies from our group suggesting the involvement of PAF in a negative feedback mechanism effective in the local regulation of vasomotor tone in anaesthetized rabbits, but exclude the participation of NO in this process.
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PMID:The acute increases in vasomotor tone and blood pressure induced by carotid artery occlusion are modulated by platelet-activating factor (PAF) independently of nitric oxide release. 952 24

Oxidation of unsaturated phosphatidylcholine (PC) produces fragmented phospholipids which have similar bioactivities as the platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-PC). Since a large number of molecular species are produced upon PC oxidation, the active ingredients have not been identified. We synthesized several short-chain PCs which are known to be characteristic PC oxidation products to test their PAF-like activity. The synthetic PCs contained palmitoyl or hexadecyl residues (both C16) in sn-1 position, and propionyl (C3), valeroyl (C5), succinyl (C4 with omega-carboxyl), glutaroyl (C5 with omega-carboxyl), or suberoyl (C8 with omega-carboxyl) residues in sn-2 position. Biological activity was measured by: (1) increase of intracellular calcium in human monocytes; (2) [3H]serotonin release from rabbit platelets; and (3) aggregation of human platelets. Specificity of the cellular response was tested by inhibition with the PAF-receptor antagonists BN 52021 and WEB 2086. Synthetic PC oxidation products activated both monocytes and platelets in a PAF-specific manner. The effective concentration varied with respect to assay system and chemical structure. In general, 1-hexadecyl-PCs were more effective than 1-palmitoyl-PCs, while increasing chain length in sn-2 position lowered biological activity. However, several 1-palmitoyl-PCs activated monocytes in concentrations between 10-8 and 10-6 M. In contrast, platelets were less susceptible to 1-palmitoyl-PCs. No significant difference was found between 2-valeroyl-PC (C5 with omega-methyl) and 2-glutaroyl-PC (C5 with omega-carboxyl). The data suggest that typical products of PC oxidation, containing propionyl, succinyl, or glutaroyl residues in sn-2 position, display PAF-like activity at micromolar concentrations.
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PMID:Stimulation of monocytes and platelets by short-chain phosphatidylcholines with and without terminal carboxyl group. 976 93


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