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Zordoky Beshay N M - - 2010
Cardiovascular diseases (CVDs) remain the leading cause of death in the developed countries. Taking into account the mounting evidence about the role of cytochrome P450 (CYP) enzymes in cardiovascular physiology, CYP polymorphisms can be considered one of the major determinants of individual susceptibility to CVDs. One of the important physiological ...
Revermann Marc - - 2010
Epoxyeicosatrienoic acids (EETs) build a family consisting of four arachidonic acid derived regioisomers that are generated by P450 epoxygenases. In the past years, growing interest in influencing EET level arose since EETs possess numerous beneficial effects in the cardiovascular system, for example, vasodilation, anti-inflammation and elicit renal and myocardial protection. ...
Anwar-mohamed Anwar - - 2010
Cytochrome P450 (CYP) generated cardioprotective metabolites, epoxyeicosatrienoic acids (EETs), and cardiotoxic metabolites, hydroxyeicosatetraenoic acids (HETEs) levels are determined by many factors, including the induction or repression of the CYP enzymes, responsible for their formation. Therefore, we examined the effect of acute inflammation on the expression of CYP epoxygenases and CYP ...
Ghosh Kumaresh - - 2010
A new anthracene labeled pyridinium amide-urea conjugate 1 has been designed and synthesized. The receptor shows a different fluorometric response with L-N-acetylvaline and L-N-acetylalanine salts in CH₃CN in contrast to the other salts of L-N-acetyl α-amino acids and (S)-α-hydroxy acids studied. Upon complexation of the tetrabutylammonium salt of L-N-acetylvaline, the ...
Adlercreutz Herman - - 2010
Rye contains more fibre and bioactive compounds than other cereals used for bread production. The fibre and compounds of the fibre complex could provide protection against breast cancer (BC). To review the evidence and theoretical background for a role of rye and some of its components in the prevention of ...
Pfister Sandra L - - 2010
Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are produced by the vascular endothelium in responses to various stimuli such as the agonists acetylcholine (ACH) or bradykinin or by shear stress which activates phospholipase A(2) to release arachidonic acid. EETs are important regulators of vascular tone and ...
Sudhahar V V Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, 53226, - - 2010
Arachidonic acid metabolites, eicosanoids, are key contributors to vascular function and improper eicosanoid regulation contributes to the progression of cardiovascular diseases. Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by epoxygenase enzymes to four regioisomers, 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. These EETs have interesting beneficial effects like vasodilation, anti-inflammation, and ...
Chaudhary Ketul R KR Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, - - 2010
Arachidonic acid, a polyunsaturated fatty acid, can be metabolized to cardioprotective epoxyeicosatrienoic acids (EETs) by cytochrome P450 epoxygenases, which are subsequently hydrolyzed to less bioactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). To study the effects of pharmacological inhibitor of sEH (sEHi), C57BL6 mice hearts were perfused in Langendorff mode ...
Jørgensen Katarina Mariann - - 2010
Platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is known to be present in excess in psoriatic skin, but its exact role is uncertain. In the present study we demonstrate for the first time the role of group VI PLA(2) in PAF-induced arachidonic acid release in highly differentiated human keratinocytes. The group IValpha ...
Kopf Phillip G PG Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wis 53226, - - 2010
Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the adrenal gland, is identical to arachidonic acid except for 2 additional carbons on the carboxyl end. Adrenic acid is metabolized by cyclooxygenases, cytochrome P450s, and lipoxygenases; however, little is known regarding the role of adrenic acid and its metabolites in ...
Vogel Robert - - 2010
The nomenclature of lipoxygenases (LOXs) is partly based on the positional specificity of arachidonic acid oxygenation, but there is no unifying concept explaining the mechanistic basis of this enzyme property. According to the triad model, Phe-353, Ile-418, and Ile-593 of the rabbit 12/15-LOX form the bottom of the substrate-binding pocket, ...
Aboutabl Mona E - - 2009
There is a strong correlation between cytochrome P450 (P450)-dependent arachidonic acid metabolism and the pathogenesis of cardiac hypertrophy. Several aryl hydrocarbon receptor (AhR) ligands were found to alter P450-dependent arachidonic acid metabolism. Here, we have investigated the effect of 3-methylcholanthrene (3-MC) and benzo(a)pyrene (BaP), two AhR ligands, on the development ...
Orido Takashi - - 2010
Nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive activity and may be suitable for treatment of colorectal cancer. A popular and potent NSAID, indomethacin, is known to cause serious side-effects, for this reason its therapeutic usefulness is limited. However, these side-effects are likely to be attributed to the additional effects of indomethacin ...
Li Juan J Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, - - 2010
Altering the splice variant composition of large-conductance Ca(2+)-activated potassium (BK) channels can alter their activity and apparent sensitivity to Ca(2+) 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 ...
Mascayano Carolina - - 2010
The lipoxygenases (LOX) are a family of non-heme iron-containing dioxygenases which catalyze the stereospecific insertion of molecular oxygen into arachidonic acid, leading to hydroxy derivatives as end products. In this work, we docked arachidonic acid and two of its competitive inhibitors, flavonoids baicalein and quercetin, into the binding pockets of ...
Zhao Jinping - - 2009
Maternal diabetes may compromise infant arachidonic acid status and development. This study tested if maternal arachidonic acid supplementation improves neurodevelopment in rat offspring. Dams were randomized into 6 groups using a 3x2 design: Saline-Placebo, streptozotocin-induced diabetes with glucose controlled at <13mmol/L, or poorly controlled at 13-20mmol/L using insulin; and fed ...
Kanamoto Hirosuke - - 2009
We detected 5-LOX (arachidonate 5-lipoxygenase) in the homogenate of Marchantia polymorpha by spectrophotometry and mass spectrometry. LC/MS/MS analysis indicated that the liverwort 5-LOX produced 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE) with arachidonic acid as a substrate. The 5-LOX activity showed a Ca(2+) response, as demonstrated for human 5-LOX. These findings suggest that the ...
Catal? Angel - - 2010
The mammalian pineal gland is a prominent secretory organ with a high metabolic activity. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. Approximately 25% of the total fatty acids present in the rat pineal ...
Ai Ding - - 2010
Derived from arachidonic acid, epoxyeicosatrienoic acids function as antihypertensive and antihypertrophic mediators in the cardiovascular system. Epoxyeicosatrienoic acids are generated by soluble epoxide hydrolase, an enzyme hydrolyzing the epoxide moiety of juvenile hormones in insects, and are endothelium-derived hyperpolarizing factors that induce vessel dilation for cardioprotection. Pharmacological inhibition and genetic ...
Morse N L - - 2009
Small individual studies report that people with learning disorders have lower than normal blood concentrations of docosahexaenoic acid and arachidonic acid. The origin and consequence of the subnormal docosahexaenoic acid have been much speculated. However, relatively little attention has been paid to the significance of the low arachidonic acid concentration. ...
Baragatti Barbara - - 2009
We have previously shown (Ref. 2) that endothelium-derived hyperpolarizing factor (EDHF) becomes functional in the fetal ductus arteriosus on removal of nitric oxide and carbon monoxide. From this, it was proposed that EDHF originates from a cytochrome P-450 (CYP450)-catalyzed reaction being inhibited by the two agents. Here, we have examined ...
Corriveau Stéphanie - - 2009
OBJECTIVE: The purpose of this study was to assess the effects of exogenous eicosanoids on spontaneous uterine contractile activity. STUDY DESIGN: Eight uterine biopsies were performed from women who were undergoing elective cesarean delivery. Tension measurements were performed in vitro on myometrial strips. Contractile activities were quantified by the calculation ...
Yamazaki Tohru - - 2009
Attenuating effects of peroxisome proliferators on the concentration of free arachidonic acid by inducing 1-acyl-2-lysophospholipid acyltransferases in the kidney were studied. The administration of the three structurally dissimilar peroxisome proliferators, 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid), di(2-ethylhexyl)phthalate, and 2,2'-(decamethylenedithio)diethanol, to rats or mice considerably increased the activities of microsomal 1-acylglycerophosphoethanolamine acyltransferase (LPEAT), ...
Wu Jason H Y - - 2009
Sesamin, the major lignan found in sesame, has been shown to increase vitamin E levels by inhibiting its metabolism via the cytochrome P450 isozyme CYP4F2. CYP4F2 and CYP4A11 are the predominant human isoforms that synthesize 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid. Considerable evidence suggests that 20-HETE may play a role ...
Chawengsub Yuttana - - 2009
Arachidonic acid (AA) is metabolized by endothelial 15-lipoxygenase (15-LO) to several vasodilatory eicosanoids such as 11,12,15-trihydroxyeicosatrienoic acid (11,12,15-THETA) and its proposed unstable precursor 15-hydroxy-11,12-epoxyeicosatrienoic acid (15-H-11,12-EETA). In the present study, the acid-stable 13-hydroxy-trans-14,15-epoxy-eicosatrienoic acid (13-H-14,15-EETA) was identified and its vascular activities characterized. Rabbit aorta, mesenteric arteries, and the combination of ...
P??rez-Chac??n Gema - - 2009
Arachidonic acid (AA) and its oxygenated derivatives, collectively known as the eicosanoids, are key mediators of a wide variety of physiological and pathophysiological states. AA, obtained from the diet or synthesized from linoleic acid, is rapidly incorporated into cellular phospholipids by the concerted action of arachidonoyl-CoA synthetase and lysophospholipid acyltransferases. ...
Kohan Alison B AB Department of Biochemistry, West Virginia University, Morgantown, 26506, - - 2009
Both polyunsaturated fatty acids and AMPK promote energy partitioning away from energy consuming processes, such as fatty acid synthesis, towards energy generating processes, such as beta-oxidation. In this report, we demonstrate that arachidonic acid activates AMPK in primary rat hepatocytes, and that this effect is p38 MAPK-dependent. Activation of AMPK ...
Gu Rui-Min - - 2009
Metabolites of arachidonic acid influence sodium chloride (NaCl) transport in the thick ascending limb. Because a 10 pS Cl channel is the major type of chloride channel in the basolateral membrane of this nephron segment, we explored the effect of arachidonic acid on this channel in cell-attached patches. Addition of ...
Signorello Maria Grazia - - 2009
Arachidonic acid can act as a second messenger regulating many cellular processes among which is nitric oxide (NO) formation. The aim of the present study was to investigate the molecular mechanisms involved in the arachidonic acid effect on platelet NO level. Thus NO, cGMP and superoxide anion level, the phosphorylation ...
Wecksler Aaron T AT Chemistry and Biochemistry Department, University of California, Santa Cruz, California 95064, - - 2009
Human reticulocyte 15-lipoxygenase-1 (15-hLO-1) and human platelet 12-lipoxygenase (12-hLO) have been implicated in a number of diseases, with differences in their relative activity potentially playing a central role. In this work, we characterize the catalytic mechanism of these two enzymes with arachidonic acid (AA) as the substrate. Using variable-temperature kinetic ...
Zhu Peijuan P Centers for Cancer Pharmacology and Excellence in Environmental Toxicology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6160, - - 2009
15(S)-Hydroperoxy-[5Z,8Z,11Z,13E]-eicosatetraenoic acid (15(S)-HpETE) undergoes homolytic decomposition to bifunctional electrophiles such as 4-oxo-2(E)-nonenal. 4-Oxo-2(E)-nonenal reacts with glutathione to form a thiadiazabicyclo-4-oxo-2(E)-nonenal-glutathione adduct (TOG). Therefore, this endogenous glutathione adduct can serve as a specific biomarker of lipid hydroperoxide-mediated 4-oxo-2(E)-nonenal formation. A monocyte/macrophage cell line was generated to constitutively express human 15-lipoxygenase-1. In ...
Pawlas Natalia - - 2009
The aim of the study was to assess neuroprotective effects of N-acetylcysteine (NAC; 100-200 microM) on cultured cortical neurons exposed to arachidonic acid (AA, 10 microM) during ischemia (oxygen-glucose deprivation). Ischemic conditions decreased neuron viability to 41-47% of normoxic controls; co-exposure with arachidonic acid further attenuated neuron viability to 36.73% ...
Hu Sherry Shu-Jung SS Department of Psychological and Brain Sciences and the Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405, - - 2009
N-arachidonoyl dopamine (NADA) is an endogenous ligand that activates the cannabinoid type 1 receptor and the transient receptor potential vanilloid type 1 channel. Two potential biosynthetic pathways for NADA have been proposed, though no conclusive evidence exists for either. The first is the direct conjugation of arachidonic acid with dopamine ...
Wei Cong - - 2009
The formation of 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE) as a product from rabbit lung 15-hydroxyprostaglandin dehydrogenase (PGDH)-mediated oxidation of 15(S)-hydroperoxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid was first reported more than 30 years ago. However, the pharmacological significance of 15-oxo-ETE formation has never been established. We have now evaluated 15-lipoxygenase (LO)-1-mediated arachidonic acid (AA) metabolism to 15-oxo-ETE ...
Chawengsub Yuttana - - 2009
Stimulation of vascular endothelial cells with agonists such as acetylcholine (ACh) or bradykinin or with shear stress activates phospholipases and releases arachidonic acid (AA). AA is metabolized by cyclooxygenases, cytochrome P-450s, and lipoxygenases (LOs) to vasoactive products. In some arteries, a substantial component of the vasodilator response is dependent on ...
Gross Garrett J - - 2009
Cytochrome P-450 (CYP) epoxygenases and their arachidonic acid (AA) metabolites, the epoxyeicosatrienoic acids (EETs), have been shown to produce marked reductions in infarct size (IS) in canine myocardium either given before an ischemic insult or at reperfusion similar to that produced in ischemic preconditioning (IPC) and postconditioning (POC) protocols. However, ...
Barbayianni Efrosini E Department of Chemistry, Laboratory of Organic Chemistry, University of Athens, Panepistimiopolis, Athens, - - 2009
A series of 2-oxoamides based on dipeptides and pseudodipeptides were synthesized and their activities towards two human intracellular phospholipases A(2) (GIVA cPLA(2) and GVIA iPLA(2)) and one human secretory phospholipase A(2) (GV sPLA(2)) were evaluated. Derivatives containing a free carboxyl group are selective GIVA cPLA(2) inhibitors. A derivative based on ...
Bianco Fabio - - 2009
We have earlier shown that microglia, the immune cells of the CNS, release microparticles from cell plasma membrane after ATP stimulation. These vesicles contain and release IL-1beta, a crucial cytokine in CNS inflammatory events. In this study, we show that microparticles are also released by astrocytes and we get insights ...
de Godoy Márcio A F - - 2009
Present studies determined the roles of the cyclooxygenase (COX) versus the lipoxygenase (LO) pathways in the metabolic pathway of arachidonic acid (AA) in the internal anal sphincter (IAS) tone. Studies were performed in the rat IAS versus the nontonic rectal smooth muscle (RSM). Indomethacin, the dual COX inhibitor, but not ...
Patel Pranav - - 2009
5-Oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) is a metabolite of the 5-lipoxygenase (5-LO) product 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE), formed by the microsomal enzyme 5-hydroxyeicosanoid dehydrogenase (5-HEDH). 5-oxo-ETE is a chemoattractant for neutrophils and eosinophils, both in vitro and in vivo. To examine the substrate selectivity of 5-HEDH and to search for potential inhibitors, we ...
Oraldi Manuela - - 2009
Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different ...
Wang Su - - 2009
Direct effects on epithelial Na+ channels (ENaC) activity by lipids, e.g., arachidonic acid (AA), eicosatetraynoic acid (ETYA), linoleic acid (LA), stearic acid (SA), hydroxyeicosatetraenoic acid (HETE), 11,12-epoxyeicosatrienoic acid (EET), (PGF2), and (PGE2), in cultured mouse cortical collecting duct (M1) cells were clarified by using single-channel recordings in this study. In ...
Anterola Aldwin - - 2009
Mosses have substantial amounts of long chain C20 polyunsaturated fatty acids, such as arachidonic and eicosapentaenoic acid, in addition to the shorter chain C18 alpha-linolenic and linoleic acids, which are typical substrates of lipoxygenases in flowering plants. To identify the fatty acid substrates used by moss lipoxygenases, eight lipoxygenase genes ...
Moodley Therishnee - - 2009
Preterm neonates are more susceptible to infection than term neonates. Arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) are biologically active components of cell membrane phospholipids. Arachidonic acid is a substrate for the synthesis of eicosanoids, potent regulators of immune function. Preterm babies may have a deficiency of arachidonic acid and ...
Dymkowska Dorota - - 2009
Arachidonic acid at micromolar concentrations produced a drastic increase of the generation of reactive oxygen species (ROS) in rat hepatoma AS-30D cells cultivated in vitro along with an increase in the incidence of apoptotic cell death. Both processes were prevented by trolox, a water-soluble tocopherol derivative, and tempol, a known ...
Jansson Janet - - 2009
The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass ...
Ren YiLin Y Division of Hypertension and Vascular Research, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202, - - 2009
In the renal cortex, the connecting tubule (CNT) returns to the glomerular hilum and contacts the afferent arteriole (Af-Art). Increasing Na delivery to the CNT dilates the Af-Art by activating epithelial Na channels, a process that we call connecting tubule glomerular feedback (CTGF). However, the mediator(s) of CTGF are unknown. ...
Rådmark Olof - - 2009
5-lipoxygenase (5-LO) catalyzes two steps in biosynthesis of leukotrienes (LTs), a group of lipid mediators of inflammation derived from arachidonic acid (AA). LT antagonists are used in treatment of asthma; more recently a potential role also in atherosclerosis has raised considerable interest. Furthermore, possible effects of 5-LO metabolites in relation ...
Spector Arthur A - - 2009
Cytochrome P450 (CYP) epoxygenases convert arachidonic acid to four epoxyeicosatrienoic acid (EET) regioisomers, 5,6-, 8,9-, 11,12-, and 14,15-EET, that function as autacrine and paracrine mediators. EETs produce vascular relaxation by activating smooth muscle large-conductance Ca2+-activated K+ channels (BKCa). In addition, they have anti-inflammatory effects on blood vessels and in the ...
Sanchez-Mejia Rene O RO Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA. - - 2008
Neuronal expression of familial Alzheimer's disease-mutant human amyloid precursor protein (hAPP) and hAPP-derived amyloid-beta (Abeta) peptides causes synaptic dysfunction, inflammation and abnormal cerebrovascular tone in transgenic mice. Fatty acids may be involved in these processes, but their contribution to Alzheimer's disease pathogenesis is uncertain. We used a lipidomics approach to ...
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