It is well recognized that the CYP-derived eicosanoids constitute a new member of the arachidonic acid cascade with important implications in the regulation of physiological and pathophysiological processes. These metabolites are formed endogenously in various tissues and exert potent biological effects on cellular functions. Studies of their role in normal and diseased cells and tissues are impeded by the difficulty in selectively targeting their synthesis or their effects, because these metabolites are generated from multiple closely related proteins of the CYP superfamily. Consequently, the development of enzyme inhibitors that target specific isoforms/reactions should aid in the study of their pathophysiological roles.. We have synthesized a series of fatty acid/arachidonic acid analogs and tested their potency and selectivity in inhibiting arachidonic acid epoxidation and ω-hydroxylation reactions in rat renal microsomes. Our study confirms that the widely used, terminal acetylenic ...
Although lithium has been used therapeutically to treat patients with bipolar disorder for over 50 years, its mechanism of action, as well as that of other drugs used to treat bipolar disorder, is not agreed upon. In the present paper, I review studies in unanaesthetized rats using a neuropharmacological approach, combined with kinetic, biochemical and molecular biology techniques, demonstrating that chronic administration of three commonly used mood stabilizers (lithium, valproic acid and carbamazepine), at therapeutically relevant doses, selectively target the brain arachidonic acid cascade. Upon chronic administration, lithium and carbamazepine decrease the binding activity of activator protein-2 and, in turn, the transcription, translation and activity of its arachidonic acid-selective calcium-dependent phospholipase A2 gene product, whereas chronic valproic acid non-competitively inhibits long-chain acyl-CoA synthetase. The net overlapping effects of the three mood stabilizers are decreased ...
Definition of Arachidonic acid cascade with photos and pictures, translations, sample usage, and additional links for more information.
Arachidonic acid supplementation in daily doses of 1,000-1,500 mg for 50 days has been well tolerated during several clinical studies, with no significant side effects reported. All common markers of health, including kidney and liver function,[35] serum lipids,[39] immunity,[40] and platelet aggregation[34] appear to be unaffected with this level and duration of use. Furthermore, higher concentrations of ARA in muscle tissue may be correlated with improved insulin sensitivity.[41] Arachidonic acid supplementation of the diets of healthy adults appears to offer no toxicity or significant safety risk. While studies looking at arachidonic acid supplementation in sedentary subjects have failed to find changes in resting inflammatory markers in doses up to 1,500 mg daily, strength-trained subjects may respond differently. One study reported a significant reduction in resting inflammation (via marker IL-6) in young men supplementing 1,000 mg/day of arachidonic acid for 50 days in combination with ...
TY - JOUR. T1 - Mechanism of thrombin-induced arachidonic acid release in osteoblast-like cells. AU - Suzuki, A.. AU - Kozawa, O.. AU - Shinoda, J.. AU - Watanabe-Tomita, Y.. AU - Saito, H.. AU - Oiso, Y.. PY - 1997/6. Y1 - 1997/6. N2 - In a previous study, we have reported that thrombin stimulates phosphatidylcholine hydrolysis by phospholipase (PL) D, but has little effect on phosphoinositide hydrolysis by PLC in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the mechanism of the thrombin-induced arachidonic acid (AA) release in MC3T3-E1 cells. Thrombin stimulated AA release dose dependently in the range between 0.1 and 1 U/ml. Quinacrine, a PLA2 inhibitor, suppressed the thrombin-induced AA release. In addition, quinacrine also suppressed the thrombin-induced prostaglandin E2 synthesis in these cells. On the other hand, propranolol, which is known to inhibit phosphatidic acid phosphohydrolase, did not affect the thrombin-induced AA release. ...
The present study was designed to determine whether or not lipoxygenase-dependent metabolites of arachidonic acid are involved in the endothelium-dependent
Purified human monocytes release and metabolize endogenous arachidonic acid (20:4) from phospholipid stores when challenged with particulate inflammatory stimuli or the calcium ionophore A23187. Using radiolabeled cultures, the percentage of total [3H]20:4 released was similar with each type of stimulus. However, the spectrum of 20:4 metabolites differed. With opsonized zymosan (OpZ) or Sephadex beads coated with IgG immune complexes (Ig-beads), the predominant product was thromboxane (25% of the total) together with smaller amounts of other cyclo-oxygenase products and lipoxygenase metabolites. Levels of thromboxane synthesis by monocytes were comparable to those by platelets, as measured by radioimmunoassay. In contrast, exposure to the nonspecific agent A23187 led to mainly lipoxygenase products (70% of the total). Monocytes isolated from mononuclear cell fractions of peripheral blood contain platelets specifically rosetted to their surfaces. These platelet contaminants were removed by ...
Arachidonic acid may trigger brain inflammation. High blood levels have been associated with a greater risk of suicide and depressive episodes. On the other hand, diets high in carbohydrate and low in fat and protein (with little or no arachidonic acid) may be associated with lower levels of anxiety and depression, according to epidemiological studies.. In one study, overweight or diabetic employees who went on a whole food, plant-based diet reported increased energy, better sleep patterns and improved mental health compared to a control group given no diet restrictions. Their work productivity also showed improvement.. A similar subsequent study of employees at 10 corporate sites showed notable improvements in depression, anxiety and emotional well-being among those following a meat-free, plant-based diet.. ...
Fas-mediated apoptosis of human leukemic U937 cells was accompanied by increased arachidonic acid (AA) and oleic acid release from membrane glycerophospholipids, indicating phospholipase A2 (PLA2) activation. During apoptosis, type IV cytosolic PLA2 (cPLA2), a PLA2 isozyme with an apparent molecular mass of 110 kDa critical for stimulus-coupled AA release, was converted to a 78-kDa fragment with concomitant loss of catalytic activity. Cleavage of cPLA2 correlated with increased caspase-3-like protease activity in apoptotic cells and was abrogated by a caspase-3 inhibitor. A mutant cPLA2 protein in which Asp522 was replaced by Asn, which aligns with the consensus sequence of the caspase-3 cleavage site (DXXD downward arrowX), was resistant to apo-ptosis-associated proteolysis. Moreover, a COOH-terminal deletion mutant of cPLA2 truncated at Asp522 comigrated with the 78-kDa fragment and exhibited no enzymatic activity. Thus, caspase-3-mediated cPLA2 cleavage eventually leads to destruction of a catalytic
TY - JOUR. T1 - Cyclooxygenase-2-mediated metabolism of arachidonic acid to 15-oxo-eicosatetraenoic acid by rat intestinal epithelial cells. AU - Seon, Hwa Lee. AU - Rangiah, Kannan. AU - Williams, Michelle V.. AU - Wehr, Angela Y.. AU - DuBois, Raymond N.. AU - Blair, Ian A.. PY - 2007/11. Y1 - 2007/11. N2 - Rat intestinal epithelial cells mat permanently express the cyclooxygenase-2 (COX-2) gene (RIES cells) were used to investigate COX-2-mediated arachidonic acid (AA) metabolism. A targeted chiral lipidomics approach was employed to quantify AA metabolites that were secreted by the cells into the culture media. When intact RIES cells were treated with calcium ionophore A-23187 (1 μM) for 1 h, 11-(R)-hydroxyeicosatetraenoic acid (HETE) was the most abundant metabolite, followed by prostaglandin (PG) E2, 15-(S)-HETE, 15-oxo-eicosatetraenoic acid (ETE), and 15-(R)-HETE. Incubation for a further 23 h after the calcium ionophore was removed resulted in a substantial increase in PGE2 ...
A complex structurally diverse series of eicosanoids arises from the metabolism of arachidonic acid. The metabolic profile is further complicated by the enantioselectivity of eicosanoid formation and the variety of regioisomers that arise. In order to investigate the metabolism of arachidonic acid in vitro or in vivo, targeted methods are advantageous in order to distinguish between the complex isomeric mixtures that can arise by different metabolic pathways. Over the last several years this targeted approach has become more popular, although there are still relatively few examples where chiral targeted approaches have been employed to directly analyze complex enantiomeric mixtures. To efficiently conduct targeted eicosanoid analyses, LC separations are coupled with collision induced dissociation (CID) and tandem mass spectrometry (MS/MS). Product ion profiles are often diagnostic for particular regioisomers. The highest sensitivity that can be achieved involves the use of selected reaction monitoring
Title: Role of Cytochrome P450 Metabolites of Arachidonic Acid in Hypertension. VOLUME: 5 ISSUE: 3. Author(s):A. Sarkis and R. J. Roman. Affiliation:Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.. Keywords:cytochrome p450, eicosanoids, hypertension, 20-hete, eets. Abstract: Considerable evidence has accumulated over the last decade implicating a role of cytochrome P450 (CYP)- dependent metabolites of arachidonic acid (AA) in the pathogenesis of hypertension. Indeed, 20-hydroxyeicosatetraenoic acid (20-HETE) is produced by vascular smooth muscle (VSM) cells and is a potent vasoconstrictor that depolarizes VSM by blocking large conductance Ca2+-activated K+ channels. In contrast, epoxyeicosatrienoic acids (EETs) are synthesized by the vascular endothelium and have opposite effects on VSM (hyperpolarization and vasodilatation). Inhibition of the synthesis of 20-HETE attenuates myogenic tone and autoregulation of blood flow and ...
The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids[1] having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derived enzymatically from the fatty acid arachidonic acid.[2] Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives. The structural differences between prostaglandins account for their different biological activities. A given prostaglandin may have different and even opposite effects in different tissues in some cases. The ability of the same prostaglandin to stimulate a reaction in one tissue and inhibit the same reaction in another tissue is determined by the type of receptor to which the prostaglandin binds. They act as autocrine or paracrine factors with their target cells present in the immediate vicinity of the site of their secretion. ...
Fat is back. Not that it ever really went away. Even when very low-fat diets were all the rage, experts recognized that certain fats were more harmful than others and some were even beneficial.. A common misperception is that omega-6 polyunsaturated fats, which are found in abundant amounts in most oils, including soybean oil, are pro-inflammatory. Meanwhile, it is thought that omega-3 polyunsaturated fats protect against inflammation. Chronic inflammation is believed to be a key process underlying many chronic diseases.. Back in the late 1970s, researchers suggested that the low incidence of heart disease among the Inuit of Canada and Alaska was related to their fat intake.1 Specifically, this population eats a diet high in the omega-3 fatty acid eicosanoic acid from fish and low in the omega-6 fatty acid arachidonic acid which is found in other types of meat.. The findings put omega-3 fats in the spotlight, giving rise to the popularity of fish oil supplements. But evidence in support of the ...
BioAssay record AID 3623 submitted by ChEMBL: Inhibition of [14C]arachidonic acid conversion to 5-HETE by broken cell 5-LO isolated from guinea pig PMN.
In the present study, we investigated whether the protective effect of FK506 and cyclosporin A (CsA) against in vitro ischemic injury of astrocytes might be mediated through attenuation of cytosolic isoform of phospholipase A(2) (cPLA(2)) expression and activity as well as inhibition of arachidonic acid (AA) release. On the 21st day in vitro, cultures of rat astrocytes were subjected to ischemia-simulating conditions (combined oxygen glucose deprivation) for 8 h and exposed to FK506 (10 - 1,000 nM) and CsA (0.25 - 10 microM). Obtained data suggest the cross-talk between the action of 0.25 - 10 microM CsA as well as 1 microM FK506 on calcineurin (CaN) and cPLA(2) in anti-apoptotic signal transduction pathways. Moreover, we have shown that immunosuppressants at these concentrations protected glial cells against ischemia-induced apoptosis through the increase of cell viability, mitochondrial function restoration, and attenuation of oxidative stress. Finally, in our study, low concentrations of FK506 (10
Topical corticosteroids and topical nonsteroidal antiinflammatory drugs (NSAIDs) are the two main options at surgeons disposal for controlling postoperative ocular inflammation. While both drug classes decrease inflammation, they have different properties and different mechanisms of action.Steroids block the inflammatory cascade at an early stage: the arachidonic acid pathway activated by tissue damage. But to be effective, steroids need to pass through cell membranes and enter the nucleus, which is limited because of their lipophobic nature. In addition, steroid side effects include intraocular pressure (IOP) elevation, delayed wound healing, and increased susceptibility to infection.NSAIDs block cyclooxygenase (COX-1 and COX-2), enzymes that convert arachidonic acid into the prostaglandins that directly mediate inflammation. NSAIDs enter cells readily and effectively shut down prostaglandin formation; within its class, the brominated NSAID bromfenac penetrates cells particularly well. ...
Prostaglandins act as short-lived localized hormones that can be released by any cell of the body during tissue, chemical, or traumatic injury, and can induce fever, inflammation, and pain, once they are present in the intercellular space. Thromboxanes, which are also hormone activators, can regulate blood vessel tone, platelet aggregation, and clot formation to increase the inflammatory response.[92,82] The inflammatory pathway is a complex biochemical pathway which, once stimulated by injury, leads to the production of these and other inflammatory mediators whose initial effect is pain and tissue destruction, followed by healing and recovery.[34,51] A major component of the inflammatory pathway is called the arachidonic acid pathway because arachidonic acid is immediately released from traumatized cellular membranes. Membrane-based arachidonic acid is transformed into prostaglandins and thromboxanes partly through the enzymatic action of cyclooxygenase (COX)[34,57]. There are two types of COX ...
Prostaglandins act as short-lived localized hormones that can be released by any cell of the body during tissue, chemical, or traumatic injury, and can induce fever, inflammation, and pain, once they are present in the intercellular space. Thromboxanes, which are also hormone activators, can regulate blood vessel tone, platelet aggregation, and clot formation to increase the inflammatory response.[92,82] The inflammatory pathway is a complex biochemical pathway which, once stimulated by injury, leads to the production of these and other inflammatory mediators whose initial effect is pain and tissue destruction, followed by healing and recovery.[34,51] A major component of the inflammatory pathway is called the arachidonic acid pathway because arachidonic acid is immediately released from traumatized cellular membranes. Membrane-based arachidonic acid is transformed into prostaglandins and thromboxanes partly through the enzymatic action of cyclooxygenase (COX)[34,57]. There are two types of COX ...
The primary American source of dietary arachidonic acid is eating meat. Meat is not bad per se. Meat becomes bad when the animal is fed junk food that makes it fat and sick. Economically, our food animals are fed the food that is most fattening. Thats because they are sold by the pound. Fatter animals are worth more in the marketplace. Our food animals are proven to become really fat on a diet of corn and/or soybeans.. Of course, fattening animal feed is a poor economic choice unless it is also cheap feed. In todays political environment, the cheapest feed is the food that is subsidized by the taxpayers; and it makes so much sense: lobbying our politicians to use taxpayer dollars to grow corn and soybeans creates a win-win situation for all, cheap meat (this is sarcasm, as noted below).. Meat, a source of complete proteins, historically was an expensive and therefore rare commodity (at least since the Agricultural Revolution, beginning about 10,000 years ago). Animals become big and fat on a ...
BioAssay record AID 274914 submitted by ChEMBL: Activity at COX1 assessed as inhibition of arachidonic acid-induced PGE2 production in J774 cells at 0.01 uM.
just read a article about arachidonic acid,,,had sum great info on it,,,,was wondering if anyone here uses it while on / off cycle and does it really work or is
COX-2 Drugs were recently approved by FDA, USA. After the discovery of COX-2, several new medicines were produced and unlike the earlier NSAIDs, the side effects were significantly reduced. COX-2 medicines were proved to be safer than COX-1 medicines. Even the doctors are prescribing these COX-2 medicines only because of their advantages over COX-1 medicines.. There is a clear difference in DNA and mRNA structures of these two but the end results are same. Even the structure of these two enzymes is almost 60% similar. The effects of these enzymes on arachidonic acid are almost same but their functionality is different. COX-2 is localized to nuclear membrane and endoplasmic reticulum. COX-1 is localized to later one only. For prostaglandin synthesis, these two use different versions of arachidonate.. The best thing about COX-2 is it doesn’t affect the prostaglandins that cause these GI problems in any way. It just stops the synthesis and the user won’t face any discomforts like GI ...
In addition to conventional treatment, there are also nutritional means to deal with inflammation. In my practice, I have helped many individuals complaining of pain from various itis diseases. We address the source of the inflammation, rather than attempting to inhibit an enzyme. The real problem may be the over-abundance of Arachidonic acid that is available to enter the PGE2 inflammatory pathway. Therefore, the first step should be to reduce the dietary consumption of Arachidonic acid, which is only found in animal products. Secondly, supplementing with the omega3 fatty acids, such as DHA and EPA, commonly found in fish oil is also beneficial. One important role of omega3 fatty acids is to keep Arachidonic acids from escaping from our own cell membranes. This may account for the anti-inflammatory role that omega three fatty acids are credited with. I have even seen dramatic results when fish oil is used topically over an inflamed area. For example, many have found relief from the pain ...
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is thought to be the predominant enzyme responsible for epoxidation of endogenous arachidonic acid in cardiac tissue. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016 ...
In contrast with mammalian cells, little is known about the control of Ca2+ entry into primitive protozoans. Here we report that Ca2+ influx in pathogenic Trypanosoma brucei can be regulated by phospholipase A2 (PLA2) and the subsequent release of arachidonic acid (AA). Several PLA2 inhibitors blocked Ca2+ entry; 3-(4-octadecyl)-benzoylacrylic acid (OBAA; IC50 0.4+/-0.1 microM) was the most potent. We identified in live trypanosomes PLA2 activity that was sensitive to OBAA and could be stimulated by Ca2+, suggesting the presence of positive feedback control. The cell-associated PLA2 activity was able to release [14C]AA from labelled phospholipid substrates. Exogenous AA (5-50 microM) also initiated Ca2+ entry in a manner that was inhibited by the Ca2+ antagonist La3+ (100 microM). Ca2+ entry did not depend on AA metabolism or protein kinase activation. The cell response was specific for AA, and fatty acids with greater saturation than tetraeicosanoic acid (AA) or with chain lengths less than C20 ...
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Arachidonic Acids Role in Stress and Shock April 3, 2012 Posted in General.. Comments Off on Arachidonic Acids Role in Stress and Shock ...
Series three - made from EPA. The number one function of series 3 prostaglandins is to save you Arachidonic Acid release from cells.. Arachidonic Acid passing thru this pathway will increase irritation and the other problems noted in Series 2. Anything we will do to decrease interest because of the AA pathway is beneficial.. Remember that Omega-threes & Omega-6s can undergo the equal pathway. The Omega-3s are transformed at a lower charge resulting in a decrease quantity. The merchandise of this pathway are then degraded by enzymes.. This machine, like many in the frame, is in constant stability. However, once in a while the manufacturing exceeds metabolism resulting in accelerated inflammation. Omega-3s are inflammatory but to a lesser quantity. Additionally, theyre produced slower ensuing in fewer numbers. This is one of the many blessings of Omega-three fatty acids.. ...
A compound of the formula ##STR1## wherein n is an integer from 2 to 4; m is an integer from 3 to 5; R is OM, OR1 or NR2 R3 where M is a pharmaceutically acceptable cation; R1, R2 and R3 are the same or different and selected from the group consisting of hydrogen, C1 -C12 branched, unbranched or cyclic alkyl, aryl and aralkyl; or R2 and R3 taken together form a group of the formula ##STR2## can be used as an inhibitor of the lipoxygenase pathway of the arachidonic acid cascade in animals.
Principal Investigator:MAIZUMI Yuji, Project Period (FY):1998 - 1999, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Biological pharmacy
Scientists in Cambridge have discovered that a brain protein called syntaxin enables fatty molecules, used widely in health supplements, to work in the brain to make it function properly. Lead Scientist, Dr Bazbek Davletov and his colleague Dr Colin Rickman from the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK report their findings in the journal Chemistry and Biology.. ...
Dumex Dulac Boouc 1 information about active ingredients, pharmaceutical forms and doses by Danone, Dumex Dulac Boouc 1 indications, usages and related health products lists
AuxInfo=1/1/N:1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22/E:(21,22)/rA:22nCCCCCCCCCCCCCCCCCCCCOO/rB:s1;s2;s3;s4;s5;d6;s7;s8;d9;s10;s11;d12;s13;s14;d15;s16;s17;s18;s19;s20;d20;/rC:-7.3658,-.6188,0;-6.6513,-.2062,0;-5.9368,-.6188,0;-5.2224,-.2062,0;-4.5079,-.6188,0;-3.7934,-.2062,0;-2.9684,-.2062,0;-2.2539,-.6188,0;-1.5395,-.2062,0;-.7145,-.2062,0;0,-.6188,0;.7145,-.2062,0;1.5395,-.2062,0;2.2539,-.6188,0;2.9684,-.2062,0;3.7934,-.2062,0;4.5079,-.6188,0;5.2224,-.2062,0;5.9368,-.6188,0;6.6513,-.2062,0;7.3658,-.6188,0;6.6513,.6188,0 ...
EaseFlex PLUS Chews with Green Lipped Mussel supplementation is for the ageing dog or active youngster that has loss of mobility through reduced joint function with Omega-3 Polyunsaturated Fatty Acids (PUFAs) which structurally mimic Arachidonic Acid metabolites.
Thromboxane A2 (TXA2) is an arachidonic acid metabolite that is released during tissue trauma and elicits platelet aggregation and vascular smooth muscle contraction. Previous research has shown that TXA2 stimulates pulmonary ...
(2011) Ugajin et al. American Journal of Pathology. Prostaglandin (PG) D2 and PGE2 are arachidonic acid metabolites that are generated though an isomerization reaction catalyzed by PG synthases. PGs have been implicated in immunologic reactions in addition to a wide range of physiological functio...
CYCLOOXYGENASE-2: Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are ...
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The present study investigated the role of arachidonic acid and acetylcholine in mediating endothelium-dependent relaxations of rabbit aorta. Isolated thoracic aortic rings were precontracted with a submaximal concentration of norepinephrine, and the effect of various agents on arachidonic acid- and acetylcholine-induced relaxations was examined. Arachidonic acid elicited a concentration-related relaxation that was potentiated by the cyclooxygenase inhibitor indomethacin. Treatment with the lipoxygenase inhibitor nordihydroguaiaretic acid completely blocked but the cytochrome P450 inhibitor metyrapone had no effect on arachidonic acid-induced relaxation. NG-Monomethyl-L-arginine and nitro-L-arginine, compounds that inhibit the nitric oxide-like endothelium-derived relaxing factor, had little or no effect on arachidonic acid-induced relaxations. In contrast, nordihydroguaiaretic acid, metyrapone, NG-monomethyl-L-arginine, and nitro-L-arginine all attenuated the relaxation to acetylcholine; ...
The physiological roles of highly unsaturated fatty acids (HUFA), mainly arachidonic acid (AA, 20:4ω6) and docosahexaenoic acid (DHA, 22:6ω3), are not completely understood. In order to study specific functions for AA and DHA, a delta-6 desaturase knockout (D6D-/-) mouse was created. D6D is a key enzyme in synthesizing HUFA from the precursor dietary essential fatty acids, linoleic acid (LA, 18:2ω6) or α-linolenic acid (ALA, 18:3ω3). By disrupting D6D expression, LA and ALA provided in the diet will not be metabolized to HUFA. Phenotype of the D6D-/- mouse is therefore specific to lack of AA and/or DHA and consists of ulcerative dermatitis, male infertility, gastrointestinal ulcers, and hepatic lipidosis. New insight on specific AA and DHA roles was established through dietary prevention of HUFA deficiency phenotype. The absence of a D6D isozyme had to be assessed before further characterizing HUFA roles with the D6D-/- mouse model. The presence of a D6D isozyme would interfere with the ...
1. Since ageing has been associated with a decrease in both immune responses and antioxidant defences, this study was undertaken to compare the glutathione peroxidase activity in peripheral blood mononuclear cells of healthy elderly and young donors. The mean value of glutathione peroxidase activity was significantly lower in the aged group (−36%) than that observed in the young control group (n = 10).. 2. This defect was accompanied by a marked increase (+106%) in the oxygenated metabolism of endogenous arachidonic acid by lipoxygenases as judged by the radiolabel associated with hydroxyeicosatetraenoic acids in [3H]arachidonic acid-prelabelled peripheral blood mononuclear cells, whereas the cyclo-oxygenase activity, estimated by the radiolabel associated with thromboxane B2, was not significantly altered.. 3. Upon stimulation by the mitogenic lectin concanavalin A, the radioactivity associated with total eicosanoids (free arachidonic acid plus hydroxyeicosatetraenoic acids plus thromboxane ...
TY - JOUR. T1 - Candida albicans stimulates arachidonic acid liberation from alveolar macrophages through α-mannan and β-glucan cell wall components. AU - Castro, M.. AU - Ralston, N. V C. AU - Morgenthaler, Timothy Ian. AU - Rohrbach, M. S.. AU - Limper, Andrew Harold. PY - 1994. Y1 - 1994. N2 - Candida albicans is an increasingly important fungal pathogen. Alveolar macrophages respond to fungal components such as zymosan by releasing arachidonic acid (AA) and AA metabolites. However, few studies have evaluated the effect of whole fungi on macrophage eicosanoid metabolism. We hypothesized that macrophages respond to C. albicans by releasing AA and generating AA metabolites as a consequence of interaction of mannose and β- glucan receptors with fungal cell wall components. [14C]AA-labeled rabbit alveolar macrophages released AA following stimulation with either live or heat-killed C. albicans. High-pressure liquid chromatography analysis revealed that 55% of the AA released was metabolized ...
A rat fecal peritonitis model of acute intraabdominal sepsis was investigated in order to evaluate the potential role of arachidonic acid metabolites in septic shock. Immunoreactive (i) Thromboxane (Tx) 8 2 , the stable metabolite of TXA2 and i6-keto-PGF 1a , the stable metabolite of prostacyclin, were measured by radioimmuonassay. plasma levels of iTXB2 rapidly increased from non-detectable (ND,200 pg/ml) to 1,066 -/+ 194 pg/ml (N=14) 1 hour after feces injction. iTxB2 then increased to 1,695 -/+ 218 pg/ml (N=16) at 4 hours and remained unchanged through 6 hours. Plasma i6-keto-PGF1a increased from ND to 3,777 -/+ 414 pg/ml (N=16) at 1 hour. Four hours after feces, i6-keto-PGF1a levels rose to 6,945 -/+ 732 pg/ml (N=16) then continued to rise to 9,465 -/+ 792 pg/ml (N=7) at 6 hours. Either essential fatty acid deficiency (arachidonic acid depletion) or indomethacin pretreatment (cyclooxygenase inhibition) significantly decreased (P,0.01) the elevations of plasma iTxB2 and i6-keto-PGF1a ...
The effect of ethanol feeding on the essential fatty acid content of tissues has been contradictory. To define the effect, we analyzed fatty acid profiles in various tissues from five miniature pigs fed daily 105 kJ basal diet/kg body wt and 146 kJ e
A recognized feature of psoriasis and other proliferative dermatoses is accumulation in your skin from the unusual arachidonic acidity metabolite, 12hydrogen through the 10-carbon of arachidonate. included regions of epidermis in psoriasis possess PPARG improved concentrations of free of charge arachidonic acid and 12-HETE markedly. Chiral analysis from the 12-HETE in psoriasis revealed that the major enantiomer is 12390C404, encompassing the major M-PFB ions at 391 (unlabeled HETE) and 399 (d8 analogue), essentially as described previously (28). Experiments with Stereospecifically Labeled Arachidonic Acids. The specific activities of the two 10-3H-labeled arachidonic acids were approximately 10,000C20,000 disintegrations per min 3H per g. The pro-[10-3H]arachidonic acid was enriched in tritium by incubation with an 8as described in principle before (29). The stereospecifically labeled arachidonic acids were admixed with [14C]arachidonic acid, which served as an internal standard for measurement ...
Arachidonate metabolites are important regulators of human breast cancer cells. Production of bioactive lipids are frequently initiated by the enzyme phospholipase A2 which releases arachidonic acid (AA) that is rapidly metabolized by cyclooxygenases (COX) or lipoxygenases (LO) to other highly potent lipids. In this study we screened a number of inhibitors which blocked specific pathways of AA metabolism for their antiproliferative activity on MCF-7 wild type and MCF-7 ADR drug resistant breast cancer cells. The toxicity of these inhibitors was further tested on human bone marrow cell proliferation. Inhibitors of LO pathways (specifically the 5-LO pathway) were most effective in blocking proliferation. Inhibitors of platelet activating factor, a byproduct of arachidonate release, were also effective antiproliferative agents. Curcumin, an inhibitor of both COX and LO pathways of eicosanoid metabolism, was 12-fold more effective in blocking proliferation of the MCF-7 ADRs cells compared to MCF-7 wild type
The phorbol ester tumor promoter (12-0-tetradecanoyl-phorbol-13-acetate (10-7-10-9 M) caused a rapid (1-3 hr after addition) release of arachidonic acid and prostaglandins E2 and F2α from chick embryo fibroblasts. This effect was inhibited by cycloheximide and puromycin. Prostaglandin release was more sensitive to inhibition than was arachidonic acid release. Indomethacin, a cyclooxygenase inhibitor, completely blocked TPA-induced prostaglandin synthesis and slightly enhanced arachidonic acid release. Despite the complete suppression of prostaglandin synthesis, indomethacin caused only a 20-30% inhibition of TPA induction of plasminogen activator. Phorbol 12,13-didecanoate, phorbol-l2,13-dibenzoate and mezerein were also potent inducers of arachidonic acid and prostaglandin release, while phorbol and 4α phorbol didecanoate were inactive. All trans retinoic acid (10-5-10-6 M) inhibited TPA-induced arachidonic acid and prostaglandin release; retinyl palmitate and β-carotene were less effective ...
The Brain Physiology and Metabolism Section (BPMS) of the National Institute on Aging (NIA) and the Clinical Neuroscience Program (CNP) of the National Institute of Neurological Disorders and Stroke (NINDS) propose to study regional brain phospholipid metabolism in young and old normal volunteers and in patients with Alzheimer disease. The method to be employed, developed from animal studies, involves the intravenous injection of a radiolabeled polyunsaturated fatty acid, [11C]arachidonic acid and measuring regional brain radioactivity using positron emission tomography (PET). A mathematical model is used to calculate regional brain incorporation coefficients k* of [11C]arachidonate into brain. These reflect brain signal transduction and membrane turnover involving phospholipids and the signal transduction and membrane turnover involving phospholipids and the activation of the enzyme, phospholipase A2. PET also will be used in the same subjects to measure regional cerebral blood flow (rCBF), a ...