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I thought I'd create this thread as a kind of archive for new arachidonic acid studies that seem particularly good.
Here are a couple:
Pharmacol Rev. 2006 Sep;58(3):591-620.
Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders.
Farooqui AA, Ong WY, Horrocks LA.
The phospholipase A(2) family includes secretory phospholipase A(2), cytosolic phospholipase A(2), plasmalogen-selective phospholipase A(2), and calcium-independent phospholipase A(2). It is generally thought that the release of arachidonic acid by cytosolic phospholipase A(2) is the rate-limiting step in the generation of eicosanoids and platelet activating factor. These lipid mediators play critical roles in the initiation and modulation of inflammation and oxidative stress. Neurological disorders, such as ischemia, spinal cord injury, Alzheimer's disease, multiple sclerosis, prion diseases, and epilepsy are characterized by inflammatory reactions, oxidative stress, altered phospholipid metabolism, accumulation of lipid peroxides, and increased phospholipase A(2) activity. Increased activities of phospholipases A(2) and generation of lipid mediators may be involved in oxidative stress and neuroinflammation associated with the above neurological disorders. Several phospholipase A(2) inhibitors have been recently discovered and used for the treatment of ischemia and other neurological diseases in cell culture and animal models. At this time very little is known about in vivo neurochemical effects, mechanism of action, or toxicity of phospholipase A(2) inhibitors in human or animal models of neurological disorders. In kainic acid-mediated neurotoxicity, the activities of phospholipase A(2) isoforms and their immunoreactivities are markedly increased and phospholipase A(2) inhibitors, quinacrine and chloroquine, arachidonyl trifluoromethyl ketone, bromoenol lactone, cytidine 5-diphosphoamines, and vitamin E, not only inhibit phospholipase A(2) activity and immunoreactivity but also prevent neurodegeneration, suggesting that phospholipase A(2) is involved in the neurodegenerative process. This also suggests that phospholipase A(2) inhibitors can be used as neuroprotectants and anti-inflammatory agents against neurodegenerative processes in neurodegenerative diseases.
Arterioscler Thromb Vasc Biol. 2006 Sep 14; [Epub ahead of print]
Phospholipase A2-Modified Low-Density Lipoprotein Activates the Phosphatidylinositol 3-Kinase-Akt Pathway and Increases Cell Survival in Monocytic Cells.
Namgaladze D, Brune B.
OBJECTIVE: Monocyte survival is an important determinant in the development of atherosclerotic lesions. We investigated the influence of phospholipase A2-modified LDL (PLA-LDL), a pro-atherogenic factor, on activation of the pro-survival kinase Akt and cell death in monocytic cells. METHODS AND RESULTS: PLA-LDL induced robust phosphorylation and activation of Akt in THP1 cells. It also attenuated oxidative stress-induced cell death, an effect abolished by phosphatidylinositol 3-kinase (PI3K) inhibition. In addition, PLA-LDL increased survival of human monocytes. We noticed that lipid products derived from LDL phospholipolysis are mediators of PLA-LDL-induced Akt activation. Arachidonic acid, which is released on phospholipase treatment of LDL, induced Akt phosphorylation and increased cell survival, whereas lysophosphatidylcholine, another compound generated by LDL phospholipolysis, induced only transient Akt phosphorylation and was cytotoxic. CONCLUSIONS: Our data indicate that PLA-LDL induces activation of the PI3K-Akt pathway and promotes monocytic cell survival, which may contribute to the pro-atherogenic effects of phospholipase A2-modified LDL.
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A recent study demonstrates how scientists are led to suggest dangerous things be done to patients because of the "essential fatty acid" notion:
"In patients with cirrhotic liver diseases, supplementation of linoleic acid and alpha-linolenic acid often does not alter the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting the necessity to directly provide these nutrients...
It is feasible to improve the liver disease-associated deficiency of AA or DHA with modest intakes of AA and DHA..."
Source: JPEN J Parenter Enteral Nutr. 2007 Nov-Dec;31(6):511-6.
Notice that they seem to be totally ignorant of the evidence that contradicts the wisdom of "supplementing" such patients with "EFAs:"
Dietary saturated fat reduces alcoholic hepatotoxicity in rats by altering fatty acid metabolism and membrane composition.
Ronis MJ, Korourian S, Zipperman M, Hakkak R, Badger TM.
Arkansas Children's Nutrition Center, Department of Pharmacology/Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. [email protected]
Rats fed a saturated fat diet are protected from experimentally induced alcoholic liver disease, but the molecular mechanisms underlying this phenomenon remain in dispute. We fed male Sprague-Dawley rats intragastrically by total enteral nutrition using diets with or without ethanol. In 1 control and 1 ethanol group, the dietary fat was corn oil at a level of 45% of total energy. In other groups, saturated fat [18:82 ratio of beef tallow:medium-chain triglyceride (MCT) oil] was substituted for corn oil at levels of 10, 20, and 30% of total energy, while keeping the total energy from fat at 45%. After 70 d, liver pathology, serum alanine aminotransferase (ALT), biochemical markers of oxidative stress, liver fatty acid composition, cytochrome P450 2E1 (CYP2E1) expression and activity and cytochrome P450 4A (CYP4A) expression were assessed. In rats fed the corn oil plus ethanol diet, hepatotoxicity was accompanied by oxidative stress. As dietary saturated fat content increased, all measures of hepatic pathology and oxidative stress were progressively reduced, including steatosis (P < 0.05). Thus, saturated fat protected rats from alcoholic liver disease in a dose-responsive fashion. Changes in dietary fat composition did not alter ethanol metabolism or CYP2E1 induction, but hepatic CYP4A levels increased markedly in rats fed the saturated fat diet. Dietary saturated fat also decreased liver triglyceride, PUFA, and total FFA concentrations (P < 0.05). Increases in dietary saturated fat increased liver membrane resistance to oxidative stress. In addition, reduced alcoholic steatosis was associated with reduced fatty acid synthesis in combination with increased CYP4A-catalyzed fatty acid oxidation and effects on lipid export. These findings may be important in the nutritional management and treatment of alcoholic liver disease. |
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Proc Natl Acad Sci U S A. 2008 Jan 9 [Epub ahead of print].
"Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells."
Abstract: Human eosinophils contain abundant amounts of 15-lipoxygenase (LO)-1. The biological role of 15-LO-1 in humans, however, is unclear. Incubation of eosinophils with arachidonic acid led to formation of a product with a UV absorbance maximum at 282 nm and shorter retention time than leukotriene (LT)C(4) in reverse-phase HPLC. Analysis with positive-ion electrospray tandem MS identified this eosinophil metabolite as 14,15-LTC(4). This metabolite could be metabolized to 14,15-LTD(4) and 14,15-LTE(4) in eosinophils. Because eosinophils are such an abundant source of these metabolites and to avoid confusion with 5-LO-derived LTs, we suggest the names eoxin (EX)C(4), -D(4), and -E(4) instead of 14,15-LTC(4), -D(4), and -E(4), respectively. Cord blood-derived mast cells and surgically removed nasal polyps from allergic subjects also produced EXC(4). Incubation of eosinophils with arachidonic acid favored the production of EXC(4), whereas challenge with calcium ionophore led to exclusive formation of LTC(4). Eosinophils produced EXC(4) after challenge with the proinflammatory agents LTC(4), prostaglandin D(2), and IL-5, demonstrating that EXC(4) can be synthesized from the endogenous pool of arachidonic acid. EXs induced increased permeability of endothelial cell monolayer in vitro, indicating that EXs can modulate and enhance vascular permeability, a hallmark of inflammation. In this model system, EXs were 100 times more potent than histamine and almost as potent as LTC(4) and LTD(4). Taken together, this article describes the formation of proinflammatory EXs, in particular in human eosinophils but also in human mast cells and nasal polyps. |
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Immunology. 2008 Jan 24 [Epub ahead of print].
"Involvement of endogenous leukotriene B(4) and platelet-activating factor in polymorphonuclear leucocyte recruitment to dermal inflammatory sites in rats."
Belanger, et al.
Abstract: A critical role for leukotriene B(4) (LTB(4)) and/or platelet-activating factor (PAF) in regulating polymorphonuclear cell (PMN) trafficking to inflammatory sites has been reported in a number of experimental inflammatory models. In vitro, newly synthesized LTB(4) and PAF were shown to act in an autocrine/paracrine or intracrine fashion to enhance intracellular arachidonic acid availability and leukotriene biosynthesis. This suggested potentially cooperative effects of these lipid mediators in regulating PMN extravasation. The present study aimed to elucidate whether endogenous LTB(4) and PAF may both act to regulate plasma extravasation and PMN trafficking to inflammatory sites in experimental inflammation. With this aim, we have used selective and potent PAF and LTB(4) receptor antagonist pretreatments in dermal and pulmonary inflammation models in rats. Our results show additive inhibitory effects of dual LTB(4) and PAF receptor blockade in either PAF- or LTB(4)-elicited cutaneous PMN accumulation compared to single-drug administration. Furthermore, the combined administration of the drugs inhibited the PMN accumulation induced by the chemically unrelated soluble agonists tumour necrosis factor-alpha and C5a. Finally, in a model of pulmonary inflammation induced by the intravenous injection of Sephadex beads, lung neutrophilia was reduced by 63% following the administration of LTB(4) and PAF antagonists, in contrast with the lack of effect of single drug administration. Our results strongly support a role of both endogenous LTB(4) and PAF in regulating PMN trafficking to inflammatory sites in various experimental conditions. |
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Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):680-5. Epub 2008 Jan 9.
Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells.
Feltenmark S, Gautam N, Brunnström A, Griffiths W, Backman L, Edenius C, Lindbom L, Björkholm M, Claesson HE.
Biolipox AB, Berzelius Väg 3, SE-171 65 Solna, Sweden.
Human eosinophils contain abundant amounts of 15-lipoxygenase (LO)-1. The biological role of 15-LO-1 in humans, however, is unclear. Incubation of eosinophils with arachidonic acid led to formation of a product with a UV absorbance maximum at 282 nm and shorter retention time than leukotriene (LT)C4 in reverse-phase HPLC. Analysis with positive-ion electrospray tandem MS identified this eosinophil metabolite as 14,15-LTC4. This metabolite could be metabolized to 14,15-LTD4 and 14,15-LTE4 in eosinophils. Because eosinophils are such an abundant source of these metabolites and to avoid confusion with 5-LO-derived LTs, we suggest the names eoxin (EX)C4, -D4, and -E4 instead of 14,15-LTC4, -D4, and -E4, respectively. Cord blood-derived mast cells and surgically removed nasal polyps from allergic subjects also produced EXC4. Incubation of eosinophils with arachidonic acid favored the production of EXC4, whereas challenge with calcium ionophore led to exclusive formation of LTC4. Eosinophils produced EXC4 after challenge with the proinflammatory agents LTC4, prostaglandin D2, and IL-5, demonstrating that EXC4 can be synthesized from the endogenous pool of arachidonic acid. EXs induced increased permeability of endothelial cell monolayer in vitro, indicating that EXs can modulate and enhance vascular permeability, a hallmark of inflammation. In this model system, EXs were 100 times more potent than histamine and almost as potent as LTC4 and LTD4. Taken together, this article describes the formation of proinflammatory EXs, in particular in human eosinophils but also in human mast cells and nasal polyps.
PMID: 18184802
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Vast number of resources (some very visual) not only for nutrition and PUFAs in the PowerPoint format (a kind of Wikipedia for presentations and teaching):
http://www.slidesonline.org/
For instance try typing "arachidonic acid" in the search box :-) |
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ORL J Otorhinolaryngol Relat Spec. 2008 May 9;70(4):242-248.
Expression of Cytosolic Phospholipase A(2) and Cyclooxygenase 2 and Their Significance in Human Oral Mucosae, Dysplasias and Squamous Cell Carcinomas.
Zhang S, Du Y, Tao J, Wu Y, Chen N.
Department ofOral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Nanjing, China.
Prostaglandin E(2) (PGE(2)) plays an important role in promoting carcinogenesis. Cytosolic phospholipase A(2) (cPLA(2)) and cyclooxygenase 2 (COX-2) are both key enzymes for PGE(2) biosynthesis. Recent evidence suggests that the coordinated function of cPLA(2) and COX-2 in the arachidonic acid pathway may contribute to the process of carcinogenesis in various tissue types. However, the concomitant effect of these enzymes on oral carcinogenesis remains unclear. In this study,we evaluated the expression of cPLA(2) and COX-2 in normal oral mucosa, dysplastic oral mucosa and squamous carcinoma (SCC) using immunohistochemistry. In an in vitro assay, Tca8113 and KB oral cancer cells were treatedwith NS-398 (a selective inhibitor of COX-2) for varying time intervals: 6, 12, 24, 48 and 72 h. The levels of cPLA(2) and COX-2 expression were evaluated by Western blot, and PGE(2) production was analyzed by radioimmunoassay. We found that cPLA(2) and COX-2 were expressed at higher levels in oral dysplasia and SCC than in normal oral mucosa. cPLA(2) expression was also found to correlate closely with COX-2 expression. Moreover, the enzymatic activities of cPLA(2) and COX-2 were gradually downregulated with longer durations of treatment with NS-398, as demonstrated by a reduction in the amount of PGE(2) production over time. Our data suggest that the coordinated activity of cPLA(2) and COX-2 contribute to the process of oral carcinogenesis, thus identifying cPLA(2) as a potential target for the prevention and treatment of oral cancers. Copyright © 2008 S. Karger AG, Basel.
PMID: 18467819
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Mol Psychiatry. 2008 Jun;13(6):585-96. Epub 2008 Mar 18.
Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?
Rao JS, Lee HJ, Rapoport SI, Bazinet RP.
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers (lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A(2) gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E(2). Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease.
PMID: 18347600
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J Urol. 2008 May;179(5):1668-75. Epub 2008 Mar 17.
The arachidonic acid pathway and its role in prostate cancer development and progression.
Patel MI, Kurek C, Dong Q.
Department of Surgery, University of Sydney, Westmead, New South Wales, Australia.
PURPOSE: The arachidonic acid pathway incorporates phospholipase, cyclooxygenase, lipoxygenase and epoxygenase enzymes. This pathway has been shown to have a major role in the development and progression of a number of cancers, including prostate cancer. We discuss the current status of research of this pathway in the area of prostate cancer, ranging from preclinical in vitro studies to human clinical trials. MATERIALS AND METHODS: We performed an online search of the current and past peer reviewed literature on prostate cancer and arachidonic acid, phospholipase, cyclooxygenase, lipoxygenase, epoxygenase, platelet activating factor, prostaglandin and eicosanoid. We retrieved and evaluated all full-length articles published in English from the 1980s to January 2007. RESULTS: Epidemiological evidence suggested that nonsteroidal anti-inflammatory drugs may decrease the risk of prostate cancer. This effect, presumably through the inhibition of cyclooxygenase-2, has been validated in preclinical studies. Cyclooxygenase-2 inhibition has also decreased the rate of prostate specific antigen increase in men with biochemical recurrence after treatment for prostate cancer. Although lipoxygenase and secretory phospholipase A2 inhibition was also effective for decreasing prostate cancer growth in preclinical studies, to our knowledge these strategies have not yet been used in clinical trials. Cytosolic phospholipase A2, platelet activating factor and epoxygenase need further investigation to determine a role in prostate cancer. CONCLUSIONS: Evolving data suggest a significant role for some areas of the arachidonic acid pathway in prostate cancer. Inhibiting 1 or a number of these enzymes in combination may hold promise for future prostate cancer treatment.
PMID: 18343442
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Inflammatory Response and Oxidative Stress in the Degeneration of Dopamine Neurons in Parkinson's Disease
The experiments performed during the third grant period were an extension of the 2nd year and were designed to provide more insights in the role of arachidonic acid release and metabolism in the oxidative stress-induced cell death caused by depletion of GSH. In addition we examined the time course of free radical generation in cells depleted of GSH. Our studies using primary mesencephalic cultures provided the following information. (l) Using selective inhibitors we showed that the release of arachidonic acid occurs early in the period of GSH depletion and depends on the activation of PLA2. (2) We showed that inhibition of PLA2 activity protects fully from damage only if applied early in the course of GSH depletion, while inhibition of arachidonic acid metabolism is protective at any time prior to cell death. This suggests that products of the metabolism of arachidonic acid are the major cause of toxicity. (3) We confirmed that products of arachidonic acid metabolism are very toxic particularly when GSH is depleted. (3) We demonstrated that hydrogen peroxide and other reactive oxygen species (ROS) accumulate in detectable amounts only a few hours prior to cell death. Accumulation begins within mitochondria and later involves processes and cell bodies. Anti-oxidants are protective when applied anytime following damage.
SOURCE:
http://stinet.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA407775
http://www.stormingmedia.us/57/5777/A577704.html |
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Clin Exp Allergy. 2008 Jul 28. [Epub ahead of print]
"Fatty acid composition abnormalities in atopic disease: evidence explored and role in the disease process examine"
Sala-Vila A, Miles EA, Calder PC.
There is a hypothesis causally linking excess intake of n-6 polyunsaturated fatty acids (PUFAs) to atopic disease. Under most dietary conditions, the main precursor of eicosanoids is the n-6 PUFA arachidonic acid (AA). AA-derived eicosanoids play many roles in sensitization to allergens and in allergic inflammation. Long chain n-3 PUFAs inhibit AA incorporation into cell membranes and inhibit AA metabolism to eicosanoids. It is hypothesized that atopy is associated with a higher n-6 PUFA status and with a low n-3 PUFA status. However, measurements of fatty acid composition do not provide a clear picture that such fatty acid abnormalities exist in atopy with no really clear pattern of altered status of a particular fatty acid or a particular fatty acid family. There are few reports of elevated linoleic acid in atopy. Some studies report lower amounts of the n-6 PUFAs, including AA, and of long chain n-3 PUFAs in atopy, although observations on this are not consistent. Taken together these data clearly do not support the hypothesis that atopy is somehow associated with a high exposure to, and status of, n-6 PUFAs. Intervention studies with n-3 PUFAs in pregnant women, infants and children suggest some clinical benefits, although how long lasting these are remains to be determined. The observation that there may be low AA status in atopy suggests that fish oil intervention, which targets AA status and metabolism, may not be ideal and that a combination of fish oil with some longer chain n-6 PUFAs may be more efficacious. |
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Yes, more research should be directed into this area instead of HIV-hunting and drug development to suppress the allergy symptoms.
I have seen a few studies showing that the delta-6 desaturase may be less active in the atopic subjects and therefore GLA supplementation helps. But they are missing the fact that if there is a defect in the Omega-6 or Omega-3 metabolism there is also a defect in the Mead acid synthesis since same enzymes are used. |
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QUOTE: A greater salivary concentration of alpha-linolenic acid (18:3 n-3) (2.82) was found in V than in M subjects (1.65) (p = 0.001), whilst arachidonic acid (20:4 n-6) was lower in V (3.93) than in M (4.52) (p = 0.045). The same difference regarding arachidonic acid was observed in the dietary fatty acid intake, also showing a significant correlation between its dietary and salivary levels in vegetarian subjects.
These results show that salivary arachidonic acid, relevant for their eicosanoid production related to the tumourigenesis process and cardiovascular diseases, is influenced by dietary fats. UNQUOTE.
Source: http://linkinghub.elsevier.com/retrieve/pii/S0003996904001761
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Here is an article about a study tentatively linking Alzheimers to too much arachadonic acid in the brain, specifically the hippoocampus Here is the study itself: Thoughts? -Drew |
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QUOTE : Lowering arachidonic acid prevents memory loss in mouse model of Alzheimer's disease
An article published online on October 19, 2008 in the journal Nature Neuroscience reported the discovery of Gladstone Institute of Neurological Disease researchers that modifying fatty acid levels in the brain has a protective effect against Alzheimer's disease in an animal model.
"Several different proteins have been implicated in Alzheimer's disease," explained Gladstone Institute Director Lennart Mucke, MD, "but we wanted to know more about the potential involvement of lipids and fatty acids."
The team compared brain fatty acid levels in normal mice with levels found in mice bred to produce human amyloid precursor protein, which is expressed in humans with familial Alzheimer's disease. "The most striking change we discovered in the Alzheimer mice was an increase in arachidonic acid and related metabolites in the hippocampus, a memory center that is affected early and severely by Alzheimer's disease," lead author Rene Sanchez-Mejia, MD noted.
Fatty acids are taken up by the brain to be incorporated into phopholipids which form the cell membrane. Arachidonic acid is released in the brain from phospholipids by an enzyme known as group IVA phospholipase A2 ( PLA2). By genetically modifying the Alzheimer mice to produce lower levels of PLA2, memory loss and behavioral abnormalities characteristic of Alzheimer's disease were prevented. "Arachidonic acid likely wreaks havoc in the Alzheimer mice by causing too much excitation, which makes neurons sick," Dr. Sanchez-Mejia remarked. "By lowering arachidonic acid levels, we are allowing neurons to function normally,"
"In general, fatty acid levels can be regulated by diet or drugs," Dr Mucke added. "Our results have important therapeutic implications because they suggest that inhibition of PLA2 activity might help prevent neurological impairments in Alzheimer's disease. But a lot more work needs to be done before this novel therapeutic strategy can be tested in humans." UNQUOTE
Source : http://www.lef.org/whatshot/2008_10.htm#Lowering-arachidonic-acid-prevents-memory-loss-Alzheimers-disease |
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This speaks to how biochemically active, and thus potentially very dangerous, arachidonic acid is. Note that it's compared to another unsaturated fatty acid that is common, both in the diet and in the body:
Proc Natl Acad Sci U S A. 2008 Nov 7. [Epub ahead of print].
"Tonic inhibition of chemotaxis in human plasma."
Malawista SE, de Boisfleury Chevance A, van Damme J, Serhan CN.
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
We found exaggerated chemotaxis in plasma treated with EDTA and thought that the EDTA might itself be inhibiting a tonic inhibitor(s) of chemotaxis. Our plasma fractionations suggested that evidence should be sought for a lipid moiety carrying this activity, and on spectrometry (LC-MS-MS together with GC-MS analyses), the biologically active but not the inactive fraction contained oleic and arachidonic acids. Because fatty acids are largely protein bound, we flooded plasma preparations with delipidated albumin, reasoning that it would bind enough fatty acids, including inhibitory ones, to counter their tonic inhibition. Indeed, we observed dramatic increases in chemotaxis. Hence, adding delipidated albumin to plasma has a similar effect to that of adding EDTA-amplification of the chemotactic response. Oleic acid in physiologic concentrations diminishes the magnifying effects of both EDTA and of delipidated albumin, and in fact diminishes the chemotactic response even without the presence of the amplifiers of chemotaxis. In contrast, arachidonic acid amplifies further the effect of EDTA but not of delipidated albumin, and this augmentation appears to be caused by an EDTA-dependent enrichment of the chemotactic gradient with leukotriene B4 (LTB4). We conclude that oleic acid, the blood levels of which vary among individuals, is at least one tonic inhibitor of chemotaxis in plasma. |
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