To see the other types of publications on this topic, follow the link: Arachidonic acid.
Journal articles on the topic 'Arachidonic acid'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Arachidonic acid.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Pickford, L. B., A. J. Polverino, and G. J. Barritt. "Evidence from studies employing radioactively labelled fatty acids that the stimulation of flux through the diacylglycerol pool is an early action of vasopressin on hepatocytes." Biochemical Journal 245, no. 1 (July 1, 1987): 211–16. http://dx.doi.org/10.1042/bj2450211.
Full textAbstract:
1. In isolated hepatocytes prelabelled with [14C]-arachidonic, -stearic, -linoleic, -oleic or -palmitic acids, vasopressin increased the amount of radioactivity present in diacylglycerols. The largest increase was observed in cells labelled with arachidonic or stearic acids. 2. In cells prelabelled with [14C]- or [3H]-arachidonic acid, the onset of the increase in radioactivity in diacylglycerols induced by vasopressin was slow, the increase was partly dependent on the presence of extracellular Ca2+, and was associated with an increase in radioactivity present in phosphatidic acid which was more rapid in onset. Vasopressin decreased the amount of [3H]arachidonyl-phosphatidylinositol 4,5-bisphosphate, but the magnitude of this decrease was less than 10% of the observed increase in radioactivity in [3H]arachidonyl-diacylglycerol. 3. The concentration of vasopressin which gave half-maximal increase in [14C]arachidonyl-diacylglycerol at low extracellular Ca2+ was 10-fold higher than that which gave half-maximal stimulation of 45Ca2+ efflux. Phenylephrine, but not glucagon, also increased the amount of [14C]arachidonyl-diacylglycerol. 4. It is concluded that an early action of vasopressin on the liver cell is to increase the flux of carbon from phospholipids, including the phosphoinositides, to diacylglycerols.
2
Patton, G. M., H. Kadowaki, H. Albadawi, H. M. Soler, and M. T. Watkins. "Effect of hypoxia on steady-state arachidonic acid metabolism in bovine aortic endothelial cells." American Journal of Physiology-Heart and Circulatory Physiology 272, no. 3 (March 1, 1997): H1426—H1436. http://dx.doi.org/10.1152/ajpheart.1997.272.3.h1426.
Full textAbstract:
At the onset of acute hypoxia, eicosanoid synthesis by bovine aortic endothelial cells (BAEC) markedly decreases, reflecting a decreased release of arachidonic acid from endogenous stores. To determine the cause of decreased arachidonic acid release, we pulse-labeled BAEC with [14C]arachidonic acid for 5 min under normoxic conditions and chased cells for 1 h under normoxic or hypoxic conditions. The 14C incorporation and specific activity (disintegrations per minute per nanomole) of three major arachidonyl molecular species (16:0-20:4, 18:1-20:4, and 18:0-20:4) of each phospholipid class were determined in cells chased under either of the two conditions. There was no relevant difference between normoxic and hypoxic cells in the metabolism of any of the arachidonyl molecular species of diacyl lipids. However, there was a marked decrease (approximately 40%) in the turnover of arachidonyl alkenylacyl phosphatidylethanolamine in the hypoxic cells. From these results, it appears that the source of arachidonic acid supporting constitutive eicosanoid synthesis in BAEC is alkenylacyl phosphatidylethanolamine and that the limiting enzyme activity determining the rate of eicosanoid synthesis is a plasmalogen-specific phospholipase A2.
3
Kakularam, Kumar R., Miquel Canyelles-Niño, Xin Chen, José M. Lluch, Àngels González-Lafont, and Hartmut Kuhn. "Functional Characterization of Mouse and Human Arachidonic Acid Lipoxygenase 15B (ALOX15B) Orthologs and of Their Mutants Exhibiting Humanized and Murinized Reaction Specificities." International Journal of Molecular Sciences 24, no. 12 (June 12, 2023): 10046. http://dx.doi.org/10.3390/ijms241210046.
Full textAbstract:
The arachidonic acid lipoxygenase 15B (ALOX15B) orthologs of men and mice form different reaction products when arachidonic acid is used as the substrate. Tyr603Asp+His604Val double mutation in mouse arachidonic acid lipoxygenase 15b humanized the product pattern and an inverse mutagenesis strategy murinized the specificity of the human enzyme. As the mechanistic basis for these functional differences, an inverse substrate binding at the active site of the enzymes has been suggested, but experimental proof for this hypothesis is still pending. Here we expressed wildtype mouse and human arachidonic acid lipoxygenase 15B orthologs as well as their humanized and murinized double mutants as recombinant proteins and analyzed the product patterns of these enzymes with different polyenoic fatty acids. In addition, in silico substrate docking studies and molecular dynamics simulation were performed to explore the mechanistic basis for the distinct reaction specificities of the different enzyme variants. Wildtype human arachidonic acid lipoxygenase 15B converted arachidonic acid and eicosapentaenoic acid to their 15-hydroperoxy derivatives but the Asp602Tyr+Val603His exchange murinized the product pattern. The inverse mutagenesis strategy in mouse arachidonic acid lipoxygenase 15b (Tyr603Asp+His604Val exchange) humanized the product pattern with these substrates, but the situation was different with docosahexaenoic acid. Here, Tyr603Asp+His604Val substitution in mouse arachidonic acid lipoxygenase 15b also humanized the specificity but the inverse mutagenesis (Asp602Tyr+Val603His) did not murinize the human enzyme. With linoleic acid Tyr603Asp+His604Val substitution in mouse arachidonic acid lipoxygenase 15b humanized the product pattern but the inverse mutagenesis in human arachidonic acid lipoxygenase 15B induced racemic product formation. Amino acid exchanges at critical positions of human and mouse arachidonic acid lipoxygenase 15B orthologs humanized/murinized the product pattern with C20 fatty acids, but this was not the case with fatty acid substrates of different chain lengths. Asp602Tyr+Val603His exchange murinized the product pattern of human arachidonic acid lipoxygenase 15B with arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. An inverse mutagenesis strategy on mouse arachidonic acid lipoxygenase 15b (Tyr603Asp+His604Val exchange) did humanize the reaction products with arachidonic acid and eicosapentaenoic acid, but not with docosahexaenoic acid.
4
Sanchez-Olea, R., M. Morales-Mulia, J. Moran, and H. Pasantes-Morales. "Inhibition by polyunsaturated fatty acids of cell volume regulation and osmolyte fluxes in astrocytes." American Journal of Physiology-Cell Physiology 269, no. 1 (July 1, 1995): C96—C102. http://dx.doi.org/10.1152/ajpcell.1995.269.1.c96.
Full textAbstract:
The polyunsaturated fatty acids, arachidonic, linoleic, and linolenic acids, were potent blockers of regulatory volume decrease (RVD) and of the swelling-activated efflux of [3H]taurine, D-[3H]aspartate, [3H]inositol, and 125I (used as marker of Cl) from rat cerebellar astrocytes in culture. The monounsaturated oleic and ricinoleic acids and saturated fatty acids were ineffective. The amino acid and 125I fluxes were similarly inhibited by fatty acids, whereas inositol release was less sensitive. Polyunsaturated fatty acids appear to directly affect RVD in trypsinized astrocytes as the inhibition was immediate and fully reversible. Blockers of the arachidonic acid metabolic pathways, indomethacin (cyclooxygenase), esculetin (lipoxygenases), and metyrapone (P-450 monooxygenases), did not prevent the effect of arachidonic acid, suggesting that further metabolism is not required for displaying the effects of arachidonic acid on RVD and osmolyte fluxes. Some blockers of arachidonic acid metabolic pathways, such as nordihydroguaiaretic acid (lipoxygenases) and naphthoflavone (P-450 monooxygenases), also exhibited marked inhibitory effects on RVD and on osmolyte fluxes. The predominant arachidonic acid metabolite in astrocytes, 12-hydroxyeicosatetraenoic acid, did not affect RVD or osmolyte fluxes. These results suggest that arachidonic acid and other polyunsaturated fatty acids directly inhibit the permeability pathways correcting cell volume after swelling in cultured astrocytes.
5
Buckley, B. J., and A. R. Whorton. "Arachidonic acid stimulates protein tyrosine phosphorylation in vascular cells." American Journal of Physiology-Cell Physiology 269, no. 6 (December 1, 1995): C1489—C1495. http://dx.doi.org/10.1152/ajpcell.1995.269.6.c1489.
Full textAbstract:
Arachidonic acid and its metabolites are important cellular mediators. In this study, we report a novel role for arachidonic acid in vascular cell signaling. We tested the effects of exogenous arachidonic acid on protein tyrosine phosphorylation in cultured vascular endothelial and smooth muscle cells. Arachidonic acid stimulated the phosphorylation of tyrosine-containing proteins of approximately 58, 93, and 120 kDa in the three cell types studied. This response was dose dependent, with a maximum effect observed with 40 microM arachidonic acid. Phosphorylation was rapid and transient, reaching a peak 0.5 min after the addition of arachidonic acid and returning to baseline by 8 min. A common set of protein substrates was phosphorylated in smooth muscle cells treated with the Ca(2+)-mobilizing agonist endothelin, concomitant with an increase in endogenous unesterified arachidonic acid. To determine whether the protein tyrosine phosphorylation was due to arachidonic acid or to a metabolite, we used inhibitors of cyclooxygenase, lipoxygenase, and epoxygenase pathways. Ibuprofen, nordihydroguaiaretic acid, eicosatriynoic and eicosatetraynoic acids, and 8-methoxypsoralen failed to inhibit the arachidonic acid-mediated response. We also found increased protein tyrosine phosphorylation after treatment with oleic, linolenic and gamma-linoleic acid. These results suggest a mechanism of protein tyrosine phosphorylation that is directly stimulated by unmetabolized unsaturated fatty acids.
6
Cubero, Francisco Javier, and Natalia Nieto. "Arachidonic acid stimulates TNFα production in Kupffer cells via a reactive oxygen species-pERK1/2-Egr1-dependent mechanism." American Journal of Physiology-Gastrointestinal and Liver Physiology 303, no. 2 (July 15, 2012): G228—G239. http://dx.doi.org/10.1152/ajpgi.00465.2011.
Full textAbstract:
Kupffer cells are a key source of mediators of alcohol-induced liver damage such as reactive oxygen species, chemokines, growth factors, and eicosanoids. Since diets rich in polyunsaturated fatty acids are a requirement for the development of alcoholic liver disease, we hypothesized that polyunsaturated fatty acids could synergize with ethanol to promote Kupffer cell activation and TNFα production, hence, contributing to liver injury. Primary Kupffer cells from control and from ethanol-fed rats incubated with arachidonic acid showed similar proliferation rates than nontreated cells; however, arachidonic acid induced phenotypic changes, lipid peroxidation, hydroperoxides, and superoxide radical generation. Similar effects occurred in human Kupffer cells. These events were greater in Kupffer cells from ethanol-fed rats, and antioxidants and inhibitors of arachidonic acid metabolism prevented them. Arachidonic acid treatment increased NADPH oxidase activity. Inhibitors of NADPH oxidase and of arachidonic acid metabolism partially prevented the increase in oxidant stress. Upon arachidonic acid stimulation, there was a rapid and sustained increase in TNFα, which was greater in Kupffer cells from ethanol-fed rats than in Kupffer cells from control rats. Arachidonic acid induced ERK1/2 phosphorylation and nuclear translocation of early growth response-1 (Egr1), and ethanol synergized with arachidonic acid to promote this effect. PD98059, a mitogen extracellular kinase 1/2 inhibitor, and curcumin, an Egr1 inhibitor, blocked the arachidonic acid-mediated upregulation of TNFα in Kupffer cells. This study unveils the mechanism whereby arachidonic acid and ethanol increase TNFα production in Kupffer cells, thus contributing to alcoholic liver disease.
7
Mandel, K. G., T. A. Bertram, M. K. Eichhold, S. C. Pepple, and M. J. Doyle. "Fatty Acid-mediated Gastroprotection Does Not Correlate with Prostaglandin Elevation in Rats Exposed to Various Chemical Insults." Veterinary Pathology 31, no. 6 (November 1994): 679–88. http://dx.doi.org/10.1177/030098589403100608.
Full textAbstract:
This study involved a comparison of activity of several long-chain fatty acids (arachidonic acid, dihomo-[γ]-linolenic acid, linoleic acid, and oleic acid) for protection against gastric mucosal damage elicited by taurocholic acid, acidified aspirin, and ethanol in rats. Each damaging agent induced gastric mucosal lesions in the corpus. Mucosal damage was induced by all agents, and all fatty acids protected the gastric mucosa; however, ethanol and arachidonic acid were the most potent damaging and protecting agents, respectively. Maximally protective doses for prevention of taurocholic acid-induced damage by arachidonic, dihomo-[γ]-linolenic, linoleic, and oleic acids were 50, 200, 100, and 200 mg/kg, respectively; however, 10 mg/kg arachidonic acid reduced lesion length by >50%, whereas minimally effective doses of the other fatty acids were ≥50 mg/kg. Similar potency differences were observed for fatty acid protection against acidified aspirin-induced gastric damage. Although all the fatty acids reduced macroscopic damage, histologic studies showed they did not totally eliminate surface mucosal damage. Microscopic analysis showed that treatment with dihomo-[γ]-linolenic acid or oleic acid attenuated depletion of neutral and acidic glycoproteins from the mucus neck cells of the gastric mucosa in response to exposure to taurocholic acid. Despite having similar gastroprotective activity, arachidonic, dihomo-[γ]-linolenic, linoleic, and oleic acids had very dissimilar abilities to elevate gastric mucosal E-series prostaglandins. Both arachidonic and dihomo-[γ]-linolenic acids elevated E-series prostaglandins, but arachidonic acid had 2–5-fold greater gastroprotective potency. Furthermore, oleic and linoleic acids, which had protective potency similar to that dihomo-[γ]-linolenic acid, did not significantly elevate prostaglandins. These studies failed to demonstrate an absolute correlation between prostaglandin elevation and gastroprotection. The results of this investigation suggest that prostaglandin elevation, although associated with gastroprotection, does not appear to be the sole mechanism for fatty acid-mediated protection of rat gastric mucosa.
8
Needleman, P., J. Truk, B. A. Jakschik, A. R. Morrison, and J. B. Lefkowith. "Arachidonic Acid Metabolism." Annual Review of Biochemistry 55, no. 1 (June 1986): 69–102. http://dx.doi.org/10.1146/annurev.bi.55.070186.000441.
Full text
9
Karara, Armando, Elizabeth Dishman, Harry Jacobson, J. R. Falck, and Jorge H. Capdevila. "Arachidonic acid epoxygenase." FEBS Letters 268, no. 1 (July 30, 1990): 227–30. http://dx.doi.org/10.1016/0014-5793(90)81014-f.
Full text
10
McGiff, John C. "Arachidonic acid metabolism." Preventive Medicine 16, no. 4 (July 1987): 503–9. http://dx.doi.org/10.1016/0091-7435(87)90064-8.
Full text
11
Thomas, G., C. Loriette, D. Pepin, J. Chambaz, and G. Bereziat. "Selective channelling of arachidonic and linoleic acids into glycerolipids of rat hepatocytes in primary culture." Biochemical Journal 256, no. 2 (December 1, 1988): 641–47. http://dx.doi.org/10.1042/bj2560641.
Full textAbstract:
Rat hepatocytes in primary culture were incubated with a mixture of linoleic and arachidonic acid at various total fatty acid/serum albumin molar ratios. Mixed fatty acids were taken up at the same rate and distributed with the same pattern as fatty acids added separately. The rates of total uptake, incorporation into hepatocyte and secreted triacylglycerols and beta-oxidation were linearly related to the fatty acid/albumin ratios, whereas the rate of incorporation into phospholipids was saturable. Neither the uptake rate nor the distribution of both fatty acids considered together varied with the arachidonic acid/linoleic acid molar ratio. Changes in this ratio and in the uptake rate led to significant variations in the respective fate of the fatty acids. The preferential channelling of arachidonic acid versus linoleic acid into beta-oxidation and phosphatidylinositol was greatest at a low uptake rate and then decreased as the uptake rose. Conversely, the preferential channelling of arachidonic acid versus linoleic acid into phosphatidylcholine, but not phosphatidylethanolamine, increased with the uptake rate. Moreover, both arachidonic acid and linoleic acid were preferentially incorporated into the 1-palmitoyl molecular species of phosphatidylcholine and phosphatidylethanolamine at a low uptake rate, and of phosphatidylcholine at a high uptake rate. This could be related to the synthesis of biliary phosphatidylcholine, of which 1-palmitoyl-2-linoleoyl and 1-palmitoyl-2-arachidonoyl are the main molecular species. Linoleic and arachidonic acid were selectively distributed into distinct metabolic pools of triacylglycerol, the intrahepatocyte pool which preferentially incorporated linoleic acid at a low uptake rate and the secreted pool in which the relative enrichment of arachidonic acid increased with the uptake rate. This strengthens the central role of hepatic secretion in the supply of arachidonic acid to peripheral tissues.
12
Monge, Patricia, Alvaro Garrido, Julio M. Rubio, Victoria Magrioti, George Kokotos, María A. Balboa, and Jesús Balsinde. "The Contribution of Cytosolic Group IVA and Calcium-Independent Group VIA Phospholipase A2s to Adrenic Acid Mobilization in Murine Macrophages." Biomolecules 10, no. 4 (April 3, 2020): 542. http://dx.doi.org/10.3390/biom10040542.
Full textAbstract:
Adrenic acid (AA), the 2-carbon elongation product of arachidonic acid, is present at significant levels in membrane phospholipids of mouse peritoneal macrophages. Despite its abundance and structural similarity to arachidonic acid, very little is known about the molecular mechanisms governing adrenic acid mobilization in cells of the innate immune system. This contrasts with the wide availability of data on arachidonic acid mobilization. In this work, we used mass-spectrometry-based lipidomic procedures to define the profiles of macrophage phospholipids that contain adrenic acid and their behavior during receptor activation. We identified the phospholipid sources from which adrenic acid is mobilized, and compared the data with arachidonic acid mobilization. Taking advantage of the use of selective inhibitors, we also showed that cytosolic group IVA phospholipase A2 is involved in the release of both adrenic and arachidonic acids. Importantly, calcium independent group VIA phospholipase A2 spared arachidonate-containing phospholipids and hydrolyzed only those that contain adrenic acid. These results identify separate mechanisms for regulating the utilization of adrenic and arachidonic acids, and suggest that the two fatty acids may serve non-redundant functions in cells.
13
Abramson, S. B., J. Leszczynska-Piziak, and G. Weissmann. "Arachidonic acid as a second messenger. Interactions with a GTP-binding protein of human neutrophils." Journal of Immunology 147, no. 1 (July 1, 1991): 231–36. http://dx.doi.org/10.4049/jimmunol.147.1.231.
Full textAbstract:
Abstract Arachidonic acid (20:4) and other cis-unsaturated fatty acids exert direct effects on a variety of cells, effects that do not depend on the metabolism of fatty acids via cyclooxygenase or lipoxygenase pathways. In these studies arachidonic acid and other cis-unsaturated fatty acids (but not trans-unsaturated or saturated fatty acids) increased the specific binding of the nonhydrolyzable analog of GTP, [35S]GTP gamma S, to purified neutrophil membrane preparations and elicited superoxide anion generation from intact neutrophils. There was a positive correlation (r = 0.70) between the capacity of fatty acids to increase nucleotide binding and to elicit the respiratory burst. Scatchard plot analysis of binding at equilibrium demonstrated an increase in the number of available GTP binding sites in the presence of 50 microM arachidonic acid. Nonsteroidal antiinflammatory agents interfered with the arachidonic acid effect on [35S]GTP gamma S binding. ADP-ribosylation of the pertussis toxin substrate Gi alpha within the plasmalemma-reduced specific [35S]GTP gamma S binding and blocked arachidonate-dependent enhancement of binding. Moreover, pertussis toxin treatment of intact neutrophils inhibited arachidonic acid-induced superoxide anion generation. The data indicate that arachidonic acid directly activates a GTP binding protein in the neutrophil plasma membrane and may thereby act as a second messenger in signal transduction.
14
Ortsäter, Henrik. "Arachidonic acid fights palmitate: new insights into fatty acid toxicity in β-cells." Clinical Science 120, no. 5 (November 19, 2010): 179–81. http://dx.doi.org/10.1042/cs20100521.
Full textAbstract:
Saturated fatty acids are toxic to pancreatic β-cells. By inducing apoptosis, they contribute to a decrease in β-cell mass, a hallmark of Type 2 diabetes. In the present issue of Clinical Science, Keane and co-workers show that the polyunsaturated fatty acid arachidonic acid protects the β-cell against the toxic effects of palmitate. As Type 2 diabetes is characterized by subclinical inflammation, and arachidonic acid and metabolites thereof are produced during states of inflammation, it is possible that pancreatic β-cells use arachidonic acid as a compound for self-protection.
15
Bouderbala, Sherazede, and Malika Bouchenak. "Olive or salmon oils affect differently the storage and transport of fatty acids by VLDL in hypercholesterolemic rats fed different proteins." Nutrition & Food Science 46, no. 2 (March 14, 2016): 190–203. http://dx.doi.org/10.1108/nfs-08-2015-0096.
Full textAbstract:
Purpose – The purpose of this study is to compare the effect of olive or salmon oil on the hepatic storage and transport of fatty acids by very-low-density lipoproteins (VLDL). Design/methodology/approach – In all, 24 male Wistar rats (80 ± 5 g) were fed a 0.5 per cent cholesterol-enriched diet with either 20 per cent casein (C) or chickpea (CP) proteins with 10 per cent olive (O) or salmon (S) oil for 28 days. Findings – In VLDL-triacyglycerols fatty acids, oleic acid content was higher in CPS as compared to that in CS or CPO and lower in CS and CPO than that in CO; linoleic acid content was higher in all groups; arachidonic acid content was higher in CS and CPO as compared to that in CO. In the liver, TG fatty acids content was lower in CPO or CPS as compared to that in CO or CS; oleic and arachidonic acid contents were lower in CPS than that in CPO; linoleic acid content was lower in CS, CPS and CPO than that in CO, CPO and CO. In liver, phospholipid fatty acid, oleic and arachidonic acid contents were lower in CPS than that in CS; oleic, linoleic and arachidonic acid contents were lower in CPO compared to that in CO. In liver, cholesteryl esters fatty acids, oleic, linoleic and arachidonic acids contents were higher in CPS as compared to that in CS; oleic, linoleic and arachidonic acid contents were lower in CS as compared to that in CO; linoleic and arachidonic acid contents were lower in CPS than that in CPO. Originality/value – A cholesterol-enriched diet containing casein or chickpea proteins combined with olive or salmon oil affects the hepatic storage and transport of polyunsaturated and monounsaturated fatty acids by VLDL.
16
Gunn, M. D., A. Sen, A. Chang, J. T. Willerson, L. M. Buja, and K. R. Chien. "Mechanisms of accumulation of arachidonic acid in cultured myocardial cells during ATP depletion." American Journal of Physiology-Heart and Circulatory Physiology 249, no. 6 (December 1, 1985): H1188—H1194. http://dx.doi.org/10.1152/ajpheart.1985.249.6.h1188.
Full textAbstract:
Previous studies have suggested that the accumulation of free arachidonic acid may be of major importance in the pathophysiology of myocardial ischemia. The purpose of the present study was to determine if the release of arachidonic acid from myocardial cells was more dependent on the extent of ATP depletion than on the inhibition of fatty acid oxidation. In addition, these studies were designed to determine if arachidonic acid release only occurred when ATP was depleted beyond a critical threshold level. To examine the relationship between arachidonic acid release and ATP depletion, cultured myocardial cells from neonatal rat hearts were labeled with [3H]arachidonate and [14C]palmitate. In response to ATP depletion with various metabolic inhibitors, [3H]arachidonic acid and [14C]palmitic acid were released from phospholipids. Phosphatidylcholine,phosphatidylethanolamine, and phosphatidic acid were the major esterified sources of the arachidonate. The release of both fatty acids was related to the extent of ATP depletion and not whether a glycolytic or respiratory inhibitor was utilized. Various combinations and doses of metabolic inhibitors were used, and experimental conditions that produced a greater than 75% decrease in ATP content were associated with the accumulation of arachidonic acid. These results suggest that an ATP-dependent step may be linked to the accumulation of arachidonic acid during myocardial ATP depletion. It is suggested that myocardial cells may release arachidonic acid directly in response to ATP depletion.
17
Li, Juan, Otor Al-Khalili, Semra Ramosevac, Douglas C. Eaton, and Donald D. Denson. "Protein-protein interaction between cPLA2 and splice variants of α-subunit of BK channels." American Journal of Physiology-Cell Physiology 298, no. 2 (February 2010): C251—C262. http://dx.doi.org/10.1152/ajpcell.00221.2009.
Full textAbstract:
Altering the splice variant composition of large-conductance Ca2+-activated potassium (BK) channels can alter their activity and apparent sensitivity to Ca2+ and other regulators of activity. We hypothesized that differences in the responsiveness to arachidonic acid of GH3 and GH4 cells was due to a difference in two splice variants, one present in GH3 cells and the other in GH4 cells. The sequences of the two splice variants differ from one another in several ways, but the largest difference is the presence or absence of 27 amino acids in the COOH terminus of the BK α-subunit. Open probability of the variant containing the 27 amino acids is significantly increased by arachidonic acid, while the variant lacking the 27 amino acids is insensitive to arachidonic acid. In addition, sensitivity of BK channels to arachidonic acid depends on cytosolic phospholipase A2 (cPLA2). Here we used the Mammalian Matchmaker two-hybrid assay and two BK α-subunit constructs with [rSlo(27)] and without [rSlo(0)] the 27-amino acid motif to determine whether cPLA2 associates with one construct [rSlo(27)] and not the other. We hypothesized that differential association of cPLA2 might explain the differing responsiveness of the two constructs and GH3 and GH4 cells to arachidonic acid. We found that cPLA2 is strongly associated with the COOH terminus of rSlo(27) and only very weakly associated with rSlo(0). We also found that arachidonic acid has a lower affinity for rSlo(0) than for rSlo(27). We conclude that the lack of response of BK channels in GH4 cells to arachidonic acid can be explained, in part, by the poor binding of cPLA2 to the COOH terminus of the rSlo(0) α-subunit, which is very similar to the splice variant found in the arachidonic acid-insensitive GH4 cells.
18
Schulz, Richard, Sonia Jancar, and David A. Cook. "Cerebral arteries can generate 5- and 15-hydroxyeicosatetraenoic acid from arachidonic acid." Canadian Journal of Physiology and Pharmacology 68, no. 7 (July 1, 1990): 807–13. http://dx.doi.org/10.1139/y90-123.
Full textAbstract:
Products of the lipoxygenase pathway have been implicated in the development of the cerebrovascular spasm that arises after subarachnoid hemorrhage. In particular the hydroperoxyeicosatetranenoic acids (HPETEs), which are unstable and break down rapidly to the corresponding 5-hydroxy acids (HETEs), are vasoconstrictor agents that mimic some aspects of cerebrovascular spasm. It is not, however, well established whether segments of cerebral artery can manufacture these products. We have studied the lipoxygenase product profile of cerebral arteries stimulated with arachidonic acid. Rings of bovine cerebral arteries were incubated in Krebs solution containing arachidonic acid. The lipoxygenase products were studied using high performance liquid chromatography. The largest peaks had the retention times of 5- and 15-HETEs, and the identity of these peaks was confirmed using specific radioimmunoassays. Stimulation with arachidonic acid resulted in a time- and dose-dependent increase in the formation of both HETEs, with 15-HETE being most abundant. The release of both HETEs was markedly reduced in the presence of AA-861, an inhibitor of lipoxygenase, but not with the cyclooxygenase inhibitor indomethacin. These data are thus consistent with our previous suggestion that the contractile activity of arachidonic acid in cerebral arteries arises, at least in part, from HPETE formation and with a possible role for these compounds in cerebral vasospasm.Key words: arachidonic acid, cerebral artery, hydroxyeicosatetraenoic acid, lipoxygenase.
19
Savva, Savvas C., Charalambos Chadjigeorgiou, Christos Hatzis, Michael Kyriakakis, George Tsimbinos, Michael Tornaritis, and Anthony Kafatos. "Association of adipose tissue arachidonic acid content with BMI and overweight status in children from Cyprus and Crete." British Journal of Nutrition 91, no. 4 (April 2004): 643–49. http://dx.doi.org/10.1079/bjn20031084.
Full textAbstract:
The relationships between n-3 and n-6 fatty acids in subcutaneous fat, BMI and overweight status were investigated in eighty-eight children from Crete and Cyprus. Overweight status, BMI and serum lipid levels were similar in children at both locations, but Cretan children had higher levels of total MUFA than Cypriot children (62·2 (sd 2·8) v. 52·2 (sd 2·8)% area, respectively, P<0·001) and consequently Cypriot children had higher levels of total saturated, polyunsaturated, trans, n-3 and n-6 fatty acids. Cypriot children had also higher levels of individual n-3 and n-6 fatty acids, specifically linoleic, α-linolenic and dihomo-γ-linolenic acids. The variance of BMI was better explained (38·2%) by adipose tissue arachidonic acid content than any other n-3 and n-6 fatty acids. Mean levels of arachidonic acid, dihomo-γ-linolenic acid and docosahexaenoic acid were higher in overweight and obese subjects. All obese subjects fell in the 4th quartile of arachidonic acid levels, whereas 88·9% of overweight subjects fell in the 3rd and 4th quartile of arachidonic acid. These results indicate positive associations between adipose tissue arachidonic acid and BMI and overweight status. Further research could clarify whether this association is causal.
20
Calder, P. C., P. Yaqoob, D. J. Harvey, A. Watts, and E. A. Newsholme. "Incorporation of fatty acids by concanavalin A-stimulated lymphocytes and the effect on fatty acid composition and membrane fluidity." Biochemical Journal 300, no. 2 (June 1, 1994): 509–18. http://dx.doi.org/10.1042/bj3000509.
Full textAbstract:
The fatty acid compositions of the neutral lipid and phospholipid fractions of rat lymph node lymphocytes were characterized. Stimulation of rat lymphocytes with the T-cell mitogen concanavalin A resulted in significant changes in the fatty acid composition of both neutral lipids and phospholipids (a decrease in the proportions of stearic, linoleic and arachidonic acids and an increase in the proportion of oleic acid). Membrane fluidity was measured using nitroxide spin-label e.s.r., and increased during culture with concanavalin A. Culturing the lymphocytes in the absence of mitogen did not affect fatty acid composition or membrane fluidity. The uptake and fate of palmitic, oleic, linoleic and arachidonic acids were studied in detail; there was a time-dependent incorporation of each fatty acid into all lipid classes but each fatty acid had a characteristic fate. Palmitic and arachidonic acids were incorporated principally into phospholipids whereas oleic and linoleic acids were incorporated in similar proportions into phospholipids and triacylglycerols. Oleic acid was incorporated mainly into phosphatidylcholine, palmitic and linoleic acids were incorporated equally into phosphatidylcholine and phosphatidylethanolamine, and arachidonic acid was incorporated mainly into phosphatidylethanolamine. Supplementation of the culture medium with particular fatty acids (myristic, palmitic, stearic, oleic, linoleic, alpha-linolenic, arachidonic, eicosapentaenoic or docosahexaenoic acid) led to enrichment of that fatty acid in both neutral lipids and phospholipids. This generated lymphocytes with phospholipids differing in saturated/unsaturated fatty acid ratio, degree of polyunsaturation, index of unsaturation and n - 6/n - 3 ratio. This method allowed the introduction into lymphocyte phospholipids of fatty acids not normally present (e.g. alpha-linolenic) or usually present in low proportions (eicosapentaenoic and docosahexaenoic). These three n - 3 polyunsaturated fatty acids replaced arachidonic acid in lymphocyte phospholipids. Fatty acid incorporation led to an alteration in lymphocyte membrane fluidity: palmitic and stearic acids decreased fluidity whereas the unsaturated fatty acids increased fluidity. It is proposed that the changes in lymphocyte phospholipid fatty acid composition and membrane fluidity brought about by culture in the presence of polyunsaturated fatty acids are responsible for the inhibition of lymphocyte functions caused by these fatty acids.
21
Alonso, M. T., A. Sanchez, and J. Garcia-Sancho. "Arachidonic acid-induced calcium influx in human platelets. Comparison with the effect of thrombin." Biochemical Journal 272, no. 2 (December 1, 1990): 435–43. http://dx.doi.org/10.1042/bj2720435.
Full textAbstract:
The effects of arachidonic acid and thrombin on calcium movements have been studied in fura-2-loaded platelets by a procedure which allows simultaneous monitoring of the uptake of manganese, a calcium surrogate for Ca2+ channels, and the release of Ca2+ from intracellular stores. Arachidonic acid induced both Ca2+ (Mn2+) entry through the plasma membrane and Ca2+ release from the intracellular stores. The release of Ca2+ was prevented by cyclo-oxygenase inhibitors and mimicked by the prostaglandin H2/thromboxane A2 receptor agonist U46619. Ca2+ (Mn2+) entry required higher concentrations of arachidonic acid and was not prevented by either cyclo-oxygenase or lipoxygenase inhibitors. Several polyunsaturated fatty acids reproduced the effect of arachidonic acid on Ca2+ (Mn2+) entry, but higher concentrations were required. The effects of maximal concentrations of arachidonic acid and thrombin on the uptake of Mn2+ were not additive. Both agonists induced the entry of Ca2+, Mn2+, Co2+ and Ba2+, but not Ni2+, which, in addition, blocked the entry of the other divalent cations. However, arachidonic acid, but not thrombin, increased a Ni2(+)-sensitive permeability to Mg2+. The effect of thrombin but not that of arachidonic acid was prevented either by pretreatment with phorbol ester or by an increase in cyclic-AMP levels. Arachidonic acid also accelerated the uptake of Mn2+ by human neutrophils, rat thymocytes and Ehrlich ascites-tumour cells.
22
Zafra, F., R. Alcantara, J. Gomeza, C. Aragon, and C. Gimenez. "Arachidonic acid inhibits glycine transport in cultured glial cells." Biochemical Journal 271, no. 1 (October 1, 1990): 237–42. http://dx.doi.org/10.1042/bj2710237.
Full textAbstract:
The effects of arachidonic acid on glycine uptake, exchange and efflux in C6 glioma cells were investigated. Arachidonic acid produced a dose-dependent inhibition of high-affinity glycine uptake. This effect was not due to a simple detergent-like action on membranes, as the inhibition of glycine transport was most pronounced with cis-unsaturated long-chain fatty acids, whereas saturated and trans-unsaturated fatty acids had relatively little or no effect. Endogenous unsaturated non-esterified fatty acids may exert a similar inhibitory effect on the transport of glycine. The mechanism for this inhibitory effect has been examined in a plasma membrane vesicle preparation derived from C6 cells, which avoids metabolic or compartmentation interferences. The results suggest that part of the selective inhibition of glycine transport by arachidonic acid could be due to the effects of the arachidonic acid on the lipid domain surrounding the carrier.
23
Scorrano, Luca, Daniele Penzo, Valeria Petronilli, Francesco Pagano, and Paolo Bernardi. "Arachidonic Acid Causes Cell Death through the Mitochondrial Permeability Transition." Journal of Biological Chemistry 276, no. 15 (December 27, 2000): 12035–40. http://dx.doi.org/10.1074/jbc.m010603200.
Full textAbstract:
We have investigated the effects of arachidonic and palmitic acids in isolated rat liver mitochondria and in rat hepatoma MH1C1 cells. We show that both compounds induce the mitochondrial permeability transition (PT). At variance from palmitic acid, however, arachidonic acid causes a PT at concentrations that do not cause PT-independent depolarization or respiratory inhibition, suggesting a specific effect on the PT pore. When added to intact MH1C1 cells, arachidonic acid but not palmitic acid caused a mitochondrial PTin situthat was accompanied by cytochromecrelease and rapidly followed by cell death. All these effects of arachidonic acid could be prevented by cyclosporin A but not by the phospholipase A2inhibitor aristolochic acid. In contrast, tumor necrosis factor α caused phospholipid hydrolysis, induction of the PT, cytochromecrelease, and cell death that could be inhibited by both cyclosporin A and aristolochic acid. These findings suggest that arachidonic acid produced by cytosolic phospholipase A2may be a mediator of tumor necrosis factor α cytotoxicityin situthrough induction of the mitochondrial PT.
24
Salem, Norman, and Peter Van Dael. "Arachidonic Acid in Human Milk." Nutrients 12, no. 3 (February 27, 2020): 626. http://dx.doi.org/10.3390/nu12030626.
Full textAbstract:
Breastfeeding is universally recommended as the optimal choice of infant feeding and consequently human milk has been extensively investigated to unravel its unique nutrient profile. The human milk lipid composition is unique and supplies specifically long-chain polyunsaturated fatty acids (LC-PUFAs), in particular, arachidonic acid (ARA, 20:4n–6) and docosahexaenoic acid (DHA, 22:6n–3). Arachidonic acid (ARA) is the most predominant long-chain polyunsaturated fatty acid in human milk, albeit at low concentrations as compared to other fatty acids. It occurs predominantly in the triglyceride form and to a lesser extent as milk fat globule membrane phospholipids. Human milk ARA levels are modulated by dietary intake as demonstrated by animal and human studies and consequently vary dependent on dietary habits among mothers and regions across the globe. ARA serves as a precursor to eicosanoids and endocannabinoids that also occur in human milk. A review of scientific and clinical studies reveals that ARA plays an important role in physiological development and its related functions during early life nutrition. Therefore, ARA is an important nutrient during infancy and childhood and, as such, appropriate attention is required regarding its nutritional status and presence in the infant diet. Data are emerging indicating considerable genetic variation in encoding for desaturases and other essential fatty acid metabolic enzymes that may influence the ARA level as well as other LC-PUFAs. Human milk from well-nourished mothers has adequate levels of both ARA and DHA to support nutritional and developmental needs of infants. In case breastfeeding is not possible and infant formula is being fed, experts recommend that both ARA and DHA are added at levels present in human milk.
25
SAUNDERS, Christine, Jeffrey M. VOIGT, and Margaret T. WEIS. "Evidence for a single non-arachidonic acid-specific fatty acyl-CoA synthetase in heart which is regulated by Mg2+." Biochemical Journal 313, no. 3 (February 1, 1996): 849–53. http://dx.doi.org/10.1042/bj3130849.
Full textAbstract:
Previous reports indicated that arachidonic acid is incorporated into the isolated perfused rabbit heart in preference to other fatty acids, and that incorporation of arachidonic acid, but not other fatty acids, is inhibited during Mg2+ depletion. In this study, we have not been able to demonstrate an arachidonic acid-specific fatty acyl-CoA synthetase in rat or rabbit heart by hydroxyapatite chromatography. Kinetic evidence was consistent with a single enzyme, as the slopes of pseudo-Hill plots were not significantly different from -1. The single fatty acyl-CoA synthetase present appears to prefer C18:0 unsaturated fatty acids to arachidonate, and had about the same affinity for C10:0–C14:0 saturated fatty acids as for arachidonate. At 35 μM arachidonate, enzyme velocity increased as the total Mg2+ was increased from 3 to 80 mM. Calculated [MgATP] indicated that the MgATP complex was not rate-limiting. At low concentrations, Mn2+ and Ni2+ supported activity, but Cu2+ and Zn2+ did not. Low Ca2+ concentrations activated only oleic acid conversion. Kinetic analysis indicated that the Vmax of the enzyme was increased with increasing concentrations of ionized Mg2+ for both oleic acid and arachidonic acid. The data are consistent with the hypothesis that Mg2+ has a direct effect on fatty acyl-CoA synthetase activity, and suggest that preference for oleic acid and arachidonic acid can be influenced by the ionic milieu.
26
Rosolowsky, M., and W. B. Campbell. "Role of PGI2 and epoxyeicosatrienoic acids in relaxation of bovine coronary arteries to arachidonic acid." American Journal of Physiology-Heart and Circulatory Physiology 264, no. 2 (February 1, 1993): H327—H335. http://dx.doi.org/10.1152/ajpheart.1993.264.2.h327.
Full textAbstract:
Metabolites of arachidonic acid regulate several physiological processes, including vascular tone. The purpose of this study was to determine which metabolites of arachidonic acid are produced by bovine coronary arteries and which may regulate coronary vascular tone. Arachidonic acid induced a concentration-related, endothelium-dependent relaxation [one-half maximum effective concentration (EC50) of 2 x 10(-7) M and a maximal relaxation of 91 +/- 2% at 10(-5) M] of bovine coronary arteries that were contracted with U-46619, a thromboxane mimetic. The concentration of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of prostaglandin I2 (PGI2), increased from 82 +/- 6 to 328 +/- 24 pg/ml with arachidonic acid (10(-5) M). Treatment with the cyclooxygenase inhibitor indomethacin attenuated arachidonic acid-induced relaxations by approximately 50% and blocked the synthesis of 6-keto-PGF1 alpha. PGI2 caused a concentration-related relaxation (EC50 of 10(-8) M and a maximal relaxation of 125 +/- 11% at 10(-7) M). BW755C, a cyclooxygenase and lipoxygenase inhibitor, inhibited arachidonic acid-induced relaxation to the same extent as indomethacin. When vessels were treated with both indomethacin and BW755C, the inhibition of relaxation was the same as either inhibitor alone. SKF 525a, a cytochrome P-450 inhibitor, reduced arachidonic acid-induced relaxation by approximately 50%. When SKF 525a was given in combination with indomethacin, the relaxation by arachidonic acid was almost completely inhibited. SKF 525a inhibited the synthesis of epoxyeicosatrienoic acids (EETs).(ABSTRACT TRUNCATED AT 250 WORDS)
27
Leslie, Christina C. "Regulation of arachidonic acid availability for eicosanoid production." Biochemistry and Cell Biology 82, no. 1 (February 1, 2004): 1–17. http://dx.doi.org/10.1139/o03-080.
Full textAbstract:
Mammalian cells have developed specific pathways for the incorporation, remodeling, and release of arachidonic acid. Acyltransferase and transacylase pathways function to regulate the levels of esterified arachidonic acid in specific phospholipid pools. There are several distinct, differentially regulated phospholipases A2 in cells that mediate agonist-induced release of arachidonic acid. These pathways are important in controlling cellular levels of free arachidonic acid. Both arachidonic acid and its oxygenated metabolites are potent bioactive mediators that regulate a myriad of physiological and pathophysiological processes.Key words: phospholipase A2, arachidonic acid, eicosanoid, phospholipid.
28
Rizzo, MT, and C. Carlo-Stella. "Arachidonic acid mediates interleukin-1 and tumor necrosis factor-alpha- induced activation of the c-jun amino-terminal kinases in stromal cells." Blood 88, no. 10 (November 15, 1996): 3792–800. http://dx.doi.org/10.1182/blood.v88.10.3792.bloodjournal88103792.
Full textAbstract:
We have previously shown that arachidonic acid mediates interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha)-induced transcription of c-jun. The signaling pathway of arachidonic acid-induced c-jun transcription was independent of protein kinase C activation and involved a tyrosine kinase-dependent process. The present study was undertaken to further elucidate the signal transduction pathway of arachidonate-induced c-jun transcription. We used a glutathione-S-transferase-c-jun fusion protein containing the aminoterminal domain of c-jun (residues 5 to 89) to explore the hypothesis that arachidonic acid stimulates c-jun amino-terminal kinase (JNK) activity in the murine stromal cell line +/+.1 LDA 11. Extracts from arachidonic acid-treated cells catalyzed phosphorylation of the c- jun fusion protein, indicating stimulation of JNK activity. Similar results were obtained when cells were challenged with IL-1 and TNF- alpha. The effect of arachidonic acid was specific, because extracts from stimulated cells failed to phosphorylate a mutated fusion protein in which serine 63 and 73 of c-jun were each substituted with leucine. Arachidonic acid induced JNK activation in a time- and dose-dependent manner that was not mimicked by saturated fatty acids such as palmitic acid or other unsaturated fatty acids from the n-3, n-6, or n-9 series. Furthermore, other lipids, such as diacylglycerol, phosphatidic acid, and C2-ceramide, failed to induce a significant increase in JNK activity. Treatment of stromal cells with propyl gallate, a dual inhibitor of lipoxygenase and cyclooxygenase enzymes, did not affect the ability of arachidonic acid to induce JNK activation. Moreover, ETYA (5,8,11,14-eicosate-traynoic acid), a nonmetabolizable arachidonate analogue, also induced JNK activation. These results are consistent with the hypothesis that the signal transduction pathway by which arachidonate stimulates c-jun transcription involves activation of the JNK cascade. Furthermore, arachidonic acid itself and not its cyclooxygenase or lipoxygenase metabolites is involved in stimulating JNK activity. Thus, arachidonic acid may act as a second messenger in mediating the effects of IL-1 and TNF-alpha in the activation of c-jun.
29
MONCADA, S., and E. A. HIGGS. "Metabolism of Arachidonic Acid." Annals of the New York Academy of Sciences 522, no. 1 Calcium Antag (March 1988): 454–63. http://dx.doi.org/10.1111/j.1749-6632.1988.tb33385.x.
Full text
30
Rosing, Ulf, and Anders Ælund. "Serum arachidonic acid levels." American Journal of Obstetrics and Gynecology 153, no. 6 (November 1985): 713–14. http://dx.doi.org/10.1016/s0002-9378(85)80272-6.
Full text
31
Feddersen, C. O., S. Chang, J. Czartalomna, and N. F. Voelkel. "Arachidonic acid causes cyclooxygenase-dependent and -independent pulmonary vasodilation." Journal of Applied Physiology 68, no. 5 (May 1, 1990): 1799–808. http://dx.doi.org/10.1152/jappl.1990.68.5.1799.
Full textAbstract:
In this study we examined the action of arachidonic acid in the isolated rat lung perfused with a cell- and protein-free physiological salt solution. When pulmonary vascular tone was elevated by hypoxia, bolus injection of a large dose of arachidonic acid (75 micrograms) caused transient vasoconstriction followed by vasodilation. When arachidonic acid (100 micrograms) was injected during normoxia and at base-line perfusion pressure (low vascular tone) or when vascular tone was elevated by KCl, arachidonic acid (50 micrograms) caused only vasoconstriction. Doses less than 7.5 micrograms caused vasodilation only when injected during hypoxic vasoconstriction and subsequent blunting of either angiotensin II- or hypoxia-induced pulmonary vasoconstriction. The higher doses of arachidonic acid (7.5 and 75 micrograms), but not the lower doses (7.5-750 ng), caused increases in effluent 6-ketoprostaglandin F1 alpha, thromboxane B2, and prostaglandin E2 and F2 alpha. 6-Ketoprostaglandin F1 alpha was the major cyclooxygenase product. Meclofenamate (10(-5) M) blocked the increased metabolite synthesis over the entire dose range of arachidonic acid tested (7.5 ng-75 micrograms). Because vasodilation immediately after arachidonic acid was cyclooxygenase-independent, we investigated whether this effect was due to the unsaturated fatty acid properties of arachidonic acid and compared its action with that of oleic acid and docosahexaenoic acid. Because neither compound mimicked the vasodilation observed with arachidonic acid, we concluded that the cyclooxygenase-independent action of arachidonic acid could not be explained by unsaturated fatty acid properties per se. Because 1-aminobenzotriazole, a cytochrome P-450 inhibitor, partially inhibited the immediate arachidonic acid-induced pulmonary vasodilation, we concluded that cytochrome P-450-dependent metabolites can account for some of the cyclooxygenase-independent vasodilation of arachidonic acid.
32
Dudley, D. T., D. E. Macfarlane, and A. A. Spector. "Depletion of arachidonic acid from GH3 cells. Effects on inositol phospholipid turnover and cellular activation." Biochemical Journal 246, no. 3 (September 15, 1987): 669–79. http://dx.doi.org/10.1042/bj2460669.
Full textAbstract:
We have adapted rat pituitary GH3 cells to grow in delipidated culture medium. In response, esterfied linoleic acid and arachidonic acid become essentially undetectable, whereas eicosa-5,8,11-trienoic acid accumulates and oleic acid increases markedly. These changes occur in all phospholipid classes, but are particularly pronounced in inositol phospholipids, where the usual stearate/arachidonate profile is replaced with oleate/eicosatrienoate (n − 9) and stearate/eicosatrienoate (n − 9). Incubation of arachidonate-depleted cells with 10 microM-arachidonic acid for only 24 h results in extensive remodelling of phospholipid fatty acids, such that close-to-normal compositions and arachidonic acid content are achieved for the inositol phospholipids. In comparison studies with arachidonic acid-depleted or -repleted cells, it was found that the arachidonate content does not affect thyrotropin-releasing-hormone (TRH)-stimulated responses measured at long time points, including [32P]Pi labelling of phosphatidylinositol and phosphatidic acid, stimulation of protein phosphorylation, and basal or TRH-stimulated prolactin release. However, transient events such as stimulated breakdown of inositol phospholipids and an initial rise in diacylglycerol are enhanced by the presence of arachidonate. These results show that arachidonic acid itself is not required for operation of the phosphatidylinositol cycle and is not an obligatory intermediate in TRH-mediated GH3 cell activation. It is possible that any structural or functional role of arachidonic acid in these processes is largely met by replacement with eicosatrienoate (n − 9). However, since arachidonate in inositol phospholipids facilitates their hydrolysis upon stimulation by TRH, arachidonic acid apparently may have a specific role in the recognition of these lipids by phospholipase C.
33
Revtyak, G. E., M. J. Hughes, A. R. Johnson, and W. B. Campbell. "Histamine stimulation of prostaglandin and HETE synthesis in human endothelial cells." American Journal of Physiology-Cell Physiology 255, no. 2 (August 1, 1988): C214—C225. http://dx.doi.org/10.1152/ajpcell.1988.255.2.c214.
Full textAbstract:
Endothelial cells (EC) cultured from human umbilical artery (UA) and vein (UV) metabolized [14C]arachidonic acid to prostaglandins (PGs), monohydroxyeicosatetraenoic acids (HETEs), and epoxyeicosatrienoic acids (EETs). Major radioactive products were identified as 6-keto-PGF1 alpha, PGE2, PGF2 alpha, 12-hydroxy heptadecatrienoic acid, 15-HETE, and 11-HETE. In addition, extracts from UV ECs contained 12-HETE, 5-HETE, 14,15-EET, and 5,6-EET as minor products, whereas extracts from UA ECs contained only 12-HETE as a minor product. UA ECs also produced metabolites comigrating with 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET. Histamine increased the release of [14C]PGs and [14C]HETEs from [14C]arachidonic acid-labeled ECs. Indomethacin, aspirin, and nordihydroguauretic acid completely inhibited synthesis of both [14C]PGs and [14C]HETEs from exogenous [14C]arachidonic acid in these cells. Microsomes metabolized [14C]arachidonic acid to the same [14C]PGs and [14C]HETEs as intact cells. Pretreatment of microsomes with indomethacin completely inhibited formation of these products. These data indicate that UA ECs and UV ECs metabolize endogenous and exogenous arachidonic acid to both PGs and HETEs. Also 15-HETE and 11-HETE appear to be synthesized by a microsomal enzyme with the properties of cyclooxygenase.
34
Meade, C. J., G. A. Turner, and P. E. Bateman. "The role of polyphosphoinositides and their breakdown products in A23187-induced release of arachidonic acid from rabbit polymorphonuclear leucocytes." Biochemical Journal 238, no. 2 (September 1, 1986): 425–36. http://dx.doi.org/10.1042/bj2380425.
Full textAbstract:
Stimulation of rabbit polymorphonuclear leucocytes with A23187 causes phospholipase C mediated breakdown of polyphosphoinositides, as evidenced by accumulation of [3H]inositol-labelled inositol bisphosphate and inositol trisphosphate. At the same time the polyphosphoinositides and the products of their breakdown, diacylglycerol and phosphatidic acid, label rapidly with radioactive arachidonic acid. Enhancement of polyphosphoinositide labelling is not as great as enhancement of diacylglycerol or phosphatidic acid labelling, suggesting additional early activation of a second independent synthetic pathway to the last named lipids. Experiments using double (3H/14C) labelling, to distinguish pools with different rates of turnover, suggest the major pool of arachidonic acid used for synthesis of lipoxygenase metabolites turns over more slowly than arachidonic acid in diacylglycerol, but at about the same rate as arachidonic acid esterified in phosphatidylcholine or phosphatidylinositol. Further, when cells are prelabelled with [14C]arachidonic acid, then stimulated for 5 min, it is only from phosphatidylcholine, and to a lesser extent phosphatidylinositol, that radiolabel is lost. Release of arachidonic acid is probably via phospholipase A2, since it is blocked by the phospholipase A2 inhibitor manoalide. The absence of accumulated lysophosphatides can be explained by reacylation and, in the case of lysophosphatidylinositol, deacylation. The importance of phospholipase A2 in phosphatidylinositol breakdown contrasts with the major role of phospholipase C in polyphosphoinositide hydrolysis. Measurements of absolute free fatty acid levels, as well as studies showing a correlation between production of radiolabelled hydroxyeicosatetraenoic acids and release of radiolabel from the phospholipid pool, both suggest that hydrolysis of arachidonic acid esterified into phospholipids is the limiting factor regulating formation of lipoxygenase metabolites. By contrast with A23187, fMet-Leu-Phe (a widely used polymorphonuclear leucocyte activator) is a poor stimulant for arachidonic acid release unless a ‘second signal’ (e.g. cytochalasin B, or a product of A23187-stimulated cells) is also present. In the presence of cytochalasin B, fMet-Leu-Phe, like A23187, stimulates release of radiolabelled arachidonic acid principally from phosphatidylcholine.
35
Shirai, Yasuhito, Kaori Kashiwagi, Keiko Yagi, Norio Sakai, and Naoaki Saito. "Distinct Effects of Fatty Acids on Translocation of γ- and ε-Subspecies of Protein Kinase C." Journal of Cell Biology 143, no. 2 (October 19, 1998): 511–21. http://dx.doi.org/10.1083/jcb.143.2.511.
Full textAbstract:
Effects of fatty acids on translocation of the γ- and ε-subspecies of protein kinase C (PKC) in living cells were investigated using their proteins fused with green fluorescent protein (GFP). γ-PKC–GFP and ε-PKC–GFP predominated in the cytoplasm, but only a small amount of γ-PKC–GFP was found in the nucleus. Except at a high concentration of linoleic acid, all the fatty acids examined induced the translocation of γ-PKC–GFP from the cytoplasm to the plasma membrane within 30 s with a return to the cytoplasm in 3 min, but they had no effect on γ-PKC–GFP in the nucleus. Arachidonic and linoleic acids induced slow translocation of ε-PKC–GFP from the cytoplasm to the perinuclear region, whereas the other fatty acids (except for palmitic acid) induced rapid translocation to the plasma membrane. The target site of the slower translocation of ε-PKC–GFP by arachidonic acid was identified as the Golgi network. The critical concentration of fatty acid that induced translocation varied among the 11 fatty acids tested. In general, a higher concentration was required to induce the translocation of ε-PKC–GFP than that of γ-PKC–GFP, the exceptions being tridecanoic acid, linoleic acid, and arachidonic acid. Furthermore, arachidonic acid and the diacylglycerol analogue (DiC8) had synergistic effects on the translocation of γ-PKC–GFP. Simultaneous application of arachidonic acid (25 μM) and DiC8 (10 μM) elicited a slow, irreversible translocation of γ-PKC– GFP from the cytoplasm to the plasma membrane after rapid, reversible translocation, but a single application of arachidonic acid or DiC8 at the same concentration induced no translocation. These findings confirm the involvement of fatty acids in the translocation of γ- and ε-PKC, and they also indicate that each subspecies has a specific targeting mechanism that depends on the extracellular signals and that a combination of intracellular activators alters the target site of PKCs.
36
Homma, Y., T. Hashimoto, Y. Nagai, and T. Takenawa. "Evidence for differential activation of arachidonic acid metabolism in formylpeptide- and macrophage-activation-factor-stimulated guinea-pig macrophages." Biochemical Journal 229, no. 3 (August 1, 1985): 643–51. http://dx.doi.org/10.1042/bj2290643.
Full textAbstract:
Alterations of phospholipid and arachidonic acid metabolism were studied by treatment of guinea-pig peritoneal-exudate macrophages with chemotactic peptide, formylmethionyl-leucylphenylalanine (fMet-Leu-Phe) and macrophage activation factor (MAF). The chemotactic peptide caused a rapid rearrangement in inositol phospholipids, including a breakdown of polyphosphoinositides within 30s, followed by a resultant formation of phosphatidylinositol (PI), diacylglycerol, phosphatidic acid and non-esterified arachidonic acid within 5 min. In addition to these sequential alterations, arachidonic acid was released mainly from PI. On the other hand, MAF induced a slow liberation of arachidonic acid, mainly from phosphatidylethanolamine (PE) and phosphatidylcholine (PC) by phospholipase A2 after the incubation period of 30 min, but not any rapid changes in phospholipids. Treatment of macrophages for 15 min with fMet-Leu-Phe produced the leukotrienes (LTs) B4, C4 and D4, prostaglandins (PG) E2 and F2 alpha and thromboxane (TX) B2. In contrast, MAF could not stimulate the production of arachidonic acid metabolites during the incubation period of 15 min, but could enhance that of PGE2, PGF2 alpha, TXB2 and hydroxyeicosatetraenoic acids at 6 h. However, the stimulated formation of LTs was not detected at any time. These results indicate that the effects of fMet-Leu-Phe on both phospholipid and arachidonic acid metabolism are very different from those mediated by MAF.
37
Jackson, M. J., J. Roberts, and R. H. T. Edwards. "Effects of dietary-fish-oil feeding on muscle growth and damage in the rat." British Journal of Nutrition 60, no. 2 (September 1988): 217–24. http://dx.doi.org/10.1079/bjn19880093.
Full textAbstract:
1. Giving diets containing 100 g fully-refined, non-hydrogenated fish oil/kg to rats caused substantial modification of skeletal-muscle-membrane fatty acid composition compared with control animals fed on an equivalent diet containing 100 g maize oil/kg.2. Total muscle arachidonic acid (20:4ω6) was reduced from 138 (sd 25) mg/g total fatty acids to 15 (sd 2) mg/ g and phospholipid arachidonic acid content showed equivalent changes.3. Reduction in muscle arachidonic acid content had no influence on the growth of individual muscles.4. Variation in muscle fatty acid composition exacerbated the response of muscle to calcium-induced damage assessed by efflux of intracellular creatine kinase (EC 2.7.3.2).5. It is concluded that metabolites of arachidonic acid are unlikely to be primary controlling factors of muscle growth or specific mediators of muscle sarcolemmal damage leading to enzyme efflux.
38
Pignatelli, P., L. Lenti, V. Sanguigni, G. Frati, I. Simeoni, P. P. Gazzaniga, F. M. Pulcinelli, and F. Violi. "Carnitine inhibits arachidonic acid turnover, platelet function, and oxidative stress." American Journal of Physiology-Heart and Circulatory Physiology 284, no. 1 (January 1, 2003): H41—H48. http://dx.doi.org/10.1152/ajpheart.00249.2002.
Full textAbstract:
Carnitine is a physiological cellular constituent that favors intracellular fatty acid transport, whose role on platelet function and O2free radicals has not been fully investigated. The aim of this study was to seek whether carnitine interferes with arachidonic acid metabolism and platelet function. Carnitine (10–50 μM) was able to dose dependently inhibit arachidonic acid incorporation into platelet phospholipids and agonist-induced arachidonic acid release. Incubation of platelets with carnitine dose dependently inhibited collagen-induced platelet aggregation, thromboxane A2formation, and Ca2+mobilization, without affecting phospholipase A2activation. Furthermore, carnitine inhibited platelet superoxide anion (O[Formula: see text]) formation elicited by arachidonic acid and collagen. To explore the underlying mechanism, arachidonic acid-stimulated platelets were incubated with NADPH. This study showed an enhanced platelet O[Formula: see text] formation, suggesting a role for NADPH oxidase in arachidonic acid-mediated platelet O[Formula: see text] production. Incubation of platelets with carnitine significantly reduced arachidonic acid-mediated NADPH oxidase activation. Moreover, the activation of protein kinase C was inhibited by 50 μM carnitine. This study shows that carnitine inhibits arachidonic acid accumulation into platelet phospholipids and in turn platelet function and arachidonic acid release elicited by platelet agonists.
39
Medow, M. S., L. Intrieri, T. Moatter, and M. E. Gerritsen. "Dexamethasone effects on microvascular endothelial cell lipid composition." American Journal of Physiology-Cell Physiology 257, no. 3 (September 1, 1989): C512—C519. http://dx.doi.org/10.1152/ajpcell.1989.257.3.c512.
Full textAbstract:
Previous studies have shown that treatment of cultured rabbit coronary microvessel endothelial (RCME) cells with dexamethasone results in a dose-, time-, and glucocorticoid-dependent inhibition of prostaglandin release. In the present study, the effects of dexamethasone on RCME membrane lipid composition and release of arachidonic acid were examined. This study demonstrated that dexamethasone treatment did not significantly alter the relative distribution of membrane phospholipids but did result in changes of fatty acid composition. There was an increase in saturated and monounsaturated fatty acids and a decrease in polyunsaturated fatty acids. Dexamethasone treatment did not reduce A23187-stimulated arachidonic acid release, despite inhibiting prostaglandin release by 50%. Studies with radiolabeled arachidonic acid suggest that dexamethasone may exert some actions on membrane remodeling, an effect that will require further investigation. Our data strongly suggest that the inhibitory actions of glucocorticoids on prostaglandin release in cultured RCME cells are not the result of a generalized inhibition of arachidonic acid release, and alternate mechanisms must therefore be considered.
40
Sheldrick, E. Linda R., Kamila Derecka, Elaine Marshall, Evonne C. Chin, Louise Hodges, D. Claire Wathes, D. Robert E. Abayasekara, and Anthony P. F. Flint. "Peroxisome-proliferator-activated receptors and the control of levels of prostaglandin-endoperoxide synthase 2 by arachidonic acid in the bovine uterus." Biochemical Journal 406, no. 1 (July 26, 2007): 175–83. http://dx.doi.org/10.1042/bj20070089.
Full textAbstract:
Arachidonic acid is a potential paracrine agent released by the uterine endometrial epithelium to induce PTGS2 [PG (prostaglandin)-endoperoxide synthase 2] in the stroma. In the present study, bovine endometrial stromal cells were used to determine whether PTGS2 is induced by arachidonic acid in stromal cells, and to investigate the potential role of PPARs (peroxisome-proliferator-activated receptors) in this effect. Arachidonic acid increased PTGS2 levels up to 7.5-fold within 6 h. The cells expressed PPARα and PPARδ (also known as PPARβ) (but not PPARγ). PTGS2 protein level was increased by PPAR agonists, including polyunsaturated fatty acids, synthetic PPAR ligands, PGA1 and NSAIDs (non-steroidal anti-inflammatory drugs) with a time course resembling that of arachidonic acid. Use of agonists and antagonists indicated PPARα (but not PPARδ or PPARγ) was responsible for PTGS2 induction. PTGS2 induction by arachidonic acid did not require PG synthesis. PTGS2 levels were increased by the PKC (protein kinase C) activators 4β-PMA and PGF2α, and the effects of arachidonic acid, NSAIDs, synthetic PPAR ligands and 4β-PMA were blocked by PKC inhibitors. This is consistent with PPAR phosphorylation by PKC. Induction of PTGS2 protein by 4β-PMA in the absence of a PPAR ligand was decreased by the NF-κB (nuclear factor κB) inhibitors MG132 and parthenolide, suggesting that PKC acted through NF-κB in addition to PPAR phosphorylation. Use of NF-κB inhibitors allowed the action of arachidonic acid as a PPAR agonist to be dissociated from an effect through PKC. The results are consistent with the hypothesis that arachidonic acid acts via PPARα to increase PTGS2 levels in bovine endometrial stromal cells.
41
Li, J. L., Y. Q. Xu, B. L. Shi, D. S. Sun, S. M. Yan, and X. Y. Guo. "Dietary chitosan affects metabolism of arachidonic acid in weaned piglets." Czech Journal of Animal Science 62, No. 2 (February 6, 2017): 58–66. http://dx.doi.org/10.17221/39/2016-cjas.
Full textAbstract:
The effects of chitosan on immune function via arachidonic acid (AA) pathway in weaned piglets were investigated. A total of 180 piglets (Duroc × Yorkshire × Landrace) were randomly assigned to 5 dietary treatments and fed a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. Results showed that serum AA, prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) contents in piglets were increased in a linear or quadratic dose-dependent manner with increasing chitosan on day 28 (P < 0.05). Chitosan increased serum cytosolic-phospholipase A2 (cPLA2) activity in a linear or quadratic dose-dependent manner on day 14 or 28, and improved 5-lipoxygenase (5-LOX) activity in a linear manner and cyclooxygenase-2 (COX-2) activity quadratically on day 28 (P < 0.05). Moreover, chitosan elevated gene expression of cPLA2 mRNA quadratically in the small intestine on days 14 and 28, increased the COX-2 mRNA expression in the duodenum or jejunum in a linear or quadratic manner on day 28, and improved the 5-LOX mRNA expression quadratically in the small intestine (P < 0.05). These results implied that the metabolism of AA was regulated by chitosan in a dose-dependent relationship, which may be one reason why chitosan affected immune function via AA pathway in weaned piglets.
42
Snyder, G. D., P. Yadagiri, and J. R. Falck. "Effect of epoxyeicosatrienoic acids on growth hormone release from somatotrophs." American Journal of Physiology-Endocrinology and Metabolism 256, no. 2 (February 1, 1989): E221—E226. http://dx.doi.org/10.1152/ajpendo.1989.256.2.e221.
Full textAbstract:
Growth hormone secretion was stimulated in vitro by products of arachidonic acid epoxygenase, the epoxyeicosatrienoic acids. 5,6-Epoxyeicosatrienoic and 14,15-epoxyeicosatrienoic acid stimulated growth hormone release from an enriched population of somatotrophs (approximately 85%) by twofold. Inhibition of arachidonic acid metabolism by indomethacin did not affect growth hormone-releasing hormone stimulation of growth hormone release. In contrast, pretreatment of somatotrophs with an 11,12-isonitrile analogue of arachidonic acid that inhibits arachidonic acid epoxygenase, resulted in a 20-25% inhibition of growth hormone-releasing hormone-stimulated growth hormone release. 14,15-Epoxyeicosatrienoic acid stimulated a concentration-dependent increase (twofold) in the cytoplasmic concentration of adenosine 3',5'-cyclic monophosphate (cAMP) in the somatotrophs. 14,15-Epoxyeicosatrienoic acid also rapidly increased the intracellular free calcium concentration in somatotrophs from resting levels (approximately 80 nM) to greater than 250 nM. Growth hormone-releasing hormone increased the free intracellular calcium to 160-180 nM. Preincubation of somatotrophs with somatostatin inhibited growth hormone-releasing hormone-stimulated growth hormone secretion, cAMP accumulation, and 14,15-epoxyeicosatrienoic acid stimulated cAMP accumulation. These data are suggestive that the epoxyeicosatrienoic acids may have a role in the secretion of growth hormone.
43
Bydlowski, S. P., R. L. Yunker, and M. T. Subbiah. "Ontogeny of 6-keto-PGF1 alpha synthesis in rabbit aorta and the effect of premature weaning." American Journal of Physiology-Heart and Circulatory Physiology 252, no. 1 (January 1, 1987): H14—H21. http://dx.doi.org/10.1152/ajpheart.1987.252.1.h14.
Full textAbstract:
A systematic study of the ontogeny of aortic 6-ketoprostaglandin F1 alpha synthesis from birth to adult life and the effect of premature weaning on this process was investigated in rabbits. Prostacyclin (PGI2) synthesis by both endogenous and exogenous arachidonic acid and its relation to aortic arachidonic acid content was determined. It was found that 1) PGI2 synthesis from endogenous arachidonic acid increased with age, whereas 2) PGI2 synthesis from exogenous arachidonic acid decreased. This correlated with a decrease in the incorporation of [14C]arachidonic acid into phospholipids with age. Aortic arachidonic acid concentration did not change from birth until 3 wk of life but increased markedly by 5 wk of age. Premature weaning caused a decrease in the synthesis of aortic PGI2 and in aortic arachidonic acid concentration initially, but the changes did not persist in later life. These studies suggest that the utilization of exogenous arachidonic acid by aorta decreases after birth perhaps due to maturity of the enzyme systems that synthesize and utilize endogenous substrates.
44
Bonney, R. C., and S. Franks. "Hydrolysis of phosphatidylinositol by human endometrium: modulating effects of steroids on arachidonic acid and 1,2-diacylglycerol release." Journal of Endocrinology 117, no. 2 (May 1988): 309–14. http://dx.doi.org/10.1677/joe.0.1170309.
Full textAbstract:
ABSTRACT Phospholipase C and 1,2-diacylglycerol lipase activities were demonstrated in human endometrium using 1-stearoyl-2-[1-14C]arachidonyl phosphatidylinositol as substrate. Phosphatidylinositol is hydrolysed by phospholipase C to inositol phosphates and to 1,2-diacylglycerol which is then further metabolized by 1,2-diacylglycerol lipase to release free arachidonic acid. In the present study the radiolabelled products formed (1,2-diacylglycerol and arachidonic acid) were measured following chloroform/methanol extraction and thin-layer chromatography. Phospholipase C activity was calcium dependent and optimal at pH 5·0–5·5 and 7·5; 1,2-diacylglycerol lipase activity was also calcium dependent, with an optimum pH of 5·5. A significant increase in 1,2-diacylglycerol production was stimulated by steroid sulphates. Pregnenolone sulphate, oestrone sulphate, testosterone sulphate and dehydroepiandrosterone sulphate stimulated 4, 3·2-1·8- and 2·6-fold increases in release respectively. Oestradiol sulphate stimulated a 25% increase in diacylglycerol release which was not significantly different from the control value. Progesterone stimulated a fourfold increase but other free steroids had no effect. Arachidonic acid release was increased in the presence of oestradiol sulphate, oestrone and oestradiol but reduced by oestrone sulphate, dehydroepiandrosterone sulphate, progesterone, dehydroepiandrosterone and, to a lesser extent, by pregnenolone sulphate and testosterone sulphate. 5-Androstene-3β, 17β-diol had no effect on the liberation of either product. This study demonstrates a potential route for the liberation of arachidonic acid from phosphatidylinositol in human endometrium. The opposing effects of steroids on phospholipase C and 1,2-diacylglycerol lipase activity could be important in regulating the release of arachidonic acid by this pathway. J. Endocr. (1988) 117, 309–314
45
Sohn, U. D., D. K. Kim, J. V. Bonventre, J. Behar, and P. Biancani. "Role of 100-kDa cytosolic PLA2 in ACh-induced contraction of cat esophageal circular muscle." American Journal of Physiology-Gastrointestinal and Liver Physiology 267, no. 3 (September 1, 1994): G433—G441. http://dx.doi.org/10.1152/ajpgi.1994.267.3.g433.
Full textAbstract:
We have shown that acetylcholine (ACh)-induced contraction of esophageal circular muscle cells is mediated by activation of protein kinase C (PKC). We now examine the role of phospholipase A2 (PLA2). ACh increases [3H]arachidonic acid release in esophageal but not in lower esophageal sphincter (LES) muscle. In addition, ACh-induced contraction of esophageal but not of LES cells was reduced by the PLA2 antagonist dimethyleicosadienoic acid and by antiserum to a 100-kDa cytosolic PLA2 (cPLA2). These data suggest that the 100-kDa cPLA2 plays a role in ACh-induced contraction of esophageal but not of LES muscle. In esophageal cells, arachidonic acid produced by PLA2 caused little contraction by itself but potentiated contraction induced by the PKC agonist diacylglycerol (DAG). The free fatty acids linoleic acid and linolenic acid also potentiated DAG-induced contraction. Indomethacin and nordihydroguaiaretic acid had no effect on arachidonic acid-induced potentiation of DAG. The potentiation of DAG-induced contraction by arachidonic acid was inhibited by the PKC inhibitor H-7, but it was not affected by the calmodulin inhibitor CGS-9343B. We conclude that a 100-kDa cPLA2 participates in ACh-induced esophageal contraction by producing arachidonic acid and potentiating DAG-induced activation of a PKC-dependent pathway.
46
Reiner, N. E., and C. J. Malemud. "Arachidonic acid metabolism by murine peritoneal macrophages infected with Leishmania donovani: in vitro evidence for parasite-induced alterations in cyclooxygenase and lipoxygenase pathways." Journal of Immunology 134, no. 1 (January 1, 1985): 556–63. http://dx.doi.org/10.4049/jimmunol.134.1.556.
Full textAbstract:
Abstract Leishmania donovani is an obligate intracellular protozoan that resides within mononuclear phagocytes of infected mammals. Affected human and rodent hosts commonly show abnormalities of T cell function, which may be related to altered macrophage physiology resulting from intracellular parasitism. To examine this possibility, we studied the metabolism of endogenous arachidonyl-phospholipids and [3H]-arachidonyl-phospholipids by murine peritoneal exudate macrophages infected with amastigotes of L. donovani. Our results indicated that infected cells synthesized increased amounts of both cyclooxygenase and lipoxygenase metabolites of arachidonic acid. Increased synthesis of immunoreactive prostaglandin (PG)E2 was evident as early as 1 to 4 hr after infection, was correlated with the fraction of cells infected, and was inhibited by sodium meclofenamate (0.2 and 20 microM) but not nordihydroguaiaretic acid (3 microM). As determined by thin-layer chromatography, infected cells also produced markedly increased amounts of prostaglandin F2 alpha (also inhibited by sodium meclofenamate) with insignificant increases in thromboxane B2 and the stable metabolite of prostacyclin, 6-oxo-PGF1 alpha. In contrast, stimulation of cells with opsonized zymosan resulted in significantly increased synthesis of all four eicosanoids. L. donovani infection was also found to induce marked increases in synthesis of lipoxygenase metabolites of arachidonic acid by infected cells. This was evidenced by increased amounts of [3H]-labeled material in cell extracts that co-migrated with authentic standards of 5 and 12/15-hydroxy-eicosate-traenoic acids in thin-layer chromatograms. Increased synthesis of these products was largely inhibited by both NDGA (3 microM) and sodium meclofenamate (20 and 0.2 microM). Additional evidence for augmentation of 5-lipoxygenase by Leishmania was provided by the demonstration of increased leukotriene-C4 in conditioned medium from infected cells. These results indicate that macrophages infected with L. donovani produce increased amounts of arachidonic acid metabolites with the potential for influencing cellular immune function and the inflammatory response to infection.
47
Llosa-Hermier, MP de la, C. Fernandez, J. Martal, and C. Hermier. "Potential role for arachidonic acid and eicosanoids in modulating progesterone secretion by ovine chorionic cells." Acta Endocrinologica 128, no. 5 (May 1993): 478–84. http://dx.doi.org/10.1530/acta.0.1280478.
Full textAbstract:
The present study was conducted to investigate whether arachidonic acid and its metabolites can modulate progesterone (P4) secretion in ovine chorionic cells. At concentrations of 7.5 μmol/l and 12.5 μmol/l, arachidonic acid caused an increase of basal P4 secretion (about 1.8-fold (p< 0.01) and 2.5-fold (p<0.001), respectively, over control). Such a stimulatory effect was suppressed when the concentration of arachidonic acid attained 25 μmol/l, and at 50 μmol/l the fatty acid led to a decline of basal P4 synthesis (about 35%, p <0.01). Phospholipase A2 (PLA2) and melittin had a similar dual effect to that observed when arachidonic acid was added exogenously. In contrast, eicosatrienoic acid (a closely related fatty acid) did not stimulate P4 secretion but inhibited it at a concentration of 50 μmol/l (about 40% inhibition, p <0.01). The possible involvement of calcium on the effects of arachidonic acid was explored. Interestingly, 3 mmol/l ethylene glycol bis(β-aminoethyl ether)-N,N,N,N′-tetraacetic acid (EGTA) and 10 μmol/l 8-N, N-diethylamino-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) further enhanced the steroidogenic effect of 12.5 μmol/l arachidonic acid (p<0.05 and p<0.01 vs the corresponding value in the absence of EGTA or TMB-8, respectively). In contrast, these agents failed to modify P4 secretion observed in the presence of 50 μmol/l arachidonic acid. We also tested the effect of inhibition of arachidonic acid metabolism via cyclooxygenase and lipoxygenase pathways. Indomethacin (10 μmol/l) failed to block the effects of arachidonic acid, but nordihydroguaiaretic acid (10 μmol/l) prevented the stimulatory action of this fatty acid. Taken together, these data suggest that arachidonic acid and its metabolites (perhaps its lipoxygenated metabolites) may be important intracellular regulators of P4 secretion in ovine chorionic cells.
48
Calder, P. C. "Polyunsaturated fatty acids and inflammation." Biochemical Society Transactions 33, no. 2 (April 1, 2005): 423–27. http://dx.doi.org/10.1042/bst0330423.
Full textAbstract:
The n–6 polyunsaturated fatty acid, arachidonic acid, is a precursor of prostaglandins, leukotrienes and related compounds that have important roles as mediators and regulators of inflammation. Consuming increased amounts of long chain n–3 polyunsaturated fatty acids (found in oily fish and fish oils) results in a partial replacement of the arachidonic acid in cell membranes by eicosapentaenoic and docosahexaenoic acids. This leads to decreased production of arachidonic acid-derived mediators. This alone is a potentially beneficial anti-inflammatory effect of n–3 fatty acids. However, n–3 fatty acids have a number of other effects that might occur downstream of altered eicosanoid production or are independent of this. For example, they result in suppressed production of pro-inflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression.
49
Høstmark, Arne. "Alpha Linolenic Acid Variability Influences the Positive Association between %Eicosapentaenoic Acid and % Arachidonic Acid in Chicken Lipids." Nutrition and Food Processing 2, no. 3 (November 8, 2019): 01–12. http://dx.doi.org/10.31579/2637-8914/016.
Full textAbstract:
Body concentrations of Arachidonic Acid (AA, 20:4 n6) and Eicosapentaenoic Acid (EPA, 20:5 n 3) are influenced by diet. Previously, we reported that the concentration range of AA and EPA might explain that %AA and %EPA are positively associated, and that variability of OA (18:1 c9) influences this association. We now investigate whether also the range of ALA (18:3 n3) might influence the association between %AA and %EPA, using data from a diet trial in chickens. A broadening (narrowing) of ALA-variability made the %AA vs. %EPA scatterplot improve (be poorer), as observed both when calculating percentages of all fatty acids, and when using ALA, AA, and EPA only in the denominator. Thus, the positive association between relative amounts of AA and EPA in breast muscle lipids of chickens is influenced by ALA variability. We raise the question of whether differences in concentration ranges between the many types of fatty acids (possibly acting via skewness) might serve as an evolutionary mechanism to ensure that percentages of fatty acids will be positively or negatively associated: a Distribution Dependent Regulation.
50
Arashi, Hiroyuki, Junichi Yamaguchi, Erisa Kawada-Watanabe, Hisao Otsuki, Haruki Sekiguchi, Hiroshi Ogawa, and Nobuhisa Hagiwara. "The Effects of Lipid-Lowering Therapy on Serum Eicosapentaenoic Acid to Arachidonic Acid Ratio: An HIJ-PROPER Sub-Analysis." Journal of Cardiovascular Pharmacology and Therapeutics 25, no. 6 (June 22, 2020): 548–55. http://dx.doi.org/10.1177/1074248420931621.
Full textAbstract:
Background: Controversy remains regarding the influence of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio. Objective: This study aimed to clarify the effects of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio in patients with acute coronary syndrome (ACS). Methods: This was a post hoc sub-analysis of the Heart Institute of Japan-PRoper level of lipid-lowering with pitavastatin and ezetimibe in ACS study. We compared the eicosapentaenoic acid/arachidonic acid ratio changes from baseline to the 3-month follow-up after contemporary lipid-lowering therapy with pitavastatin + ezetimibe therapy and pitavastatin mono-therapy. Results: Among patients with ACS and dyslipidemia, the eicosapentaenoic acid/arachidonic acid increased significantly in the pitavastatin mono-therapy group (0.40 ± 0.26 to 0.46 ± 0.34, P < .0001) but did not increase in the pitavastatin + ezetimibe group (0.37 ± 0.22 to 0.38 ± 0.27, P = .18). When the analysis was limited to patients who received 2 mg/day of pitavastatin during the follow-up period, these trends in changes of the eicosapentaenoic acid/arachidonic acid ratio remained unchanged. Multivariate analysis showed that ezetimibe use ( P = .005; β = 0.09), ST-elevation myocardial infarction ( P = .04; β = −0.01), and baseline low-density lipoprotein cholesterol (LDL-C) level ( P = .0003; β = 0.12) were independent predictors of the percentage change in the eicosapentaenoic acid/arachidonic acid ratio. These trends were similar even when the analysis was limited to patients who did not take statins at enrollment. Conclusion: Standard lipid-lowering therapy with pitavastatin mono-therapy improved the eicosapentaenoic acid/arachidonic acid ratio for patients with ACS. Intensive lipid-lowering therapy with pitavastatin + ezetimibe did not improve the eicosapentaenoic acid/arachidonic acid ratio, although LDL-C decreased significantly. Inhibition of the improvement in the eicosapentaenoic acid/arachidonic acid ratio by adding ezetimibe may affect cardiovascular disease prognosis.