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Knights Kathleen M - - 2005
The exact mechanism(s) of NSAID-induced nephrotoxicity remains unclear, but most theories centre on the initial inhibition of COX and the subsequent perturbation of the numerous actions of COX in the kidney. Since the nineteenth century no NSAIDs have been developed that are devoid of renal adverse effects, including the COX-2 ...
Du Liping - - 2006
The epidermis expresses cyclooxygenases, lipoxygenases, and cytochromes P450, which utilize arachidonic acid to generate a diverse array of lipid mediators affecting epidermal cellular differentiation and functions. Recent studies show that mouse epidermis expresses CYP2B19, a keratinocyte-specific epoxygenase that generates 11,12- and 14,15-epoxyeicosatrienoic (EET) acids from arachidonate. We studied CYP2B19-dependent metabolism ...
Xiang Lusha - - 2006
These studies tested the hypothesis that in obese Zucker rats (OZRs), a model of metabolic syndrome, the impaired functional vasodilation is due to increased thromboxane receptor (TP)-mediated vasoconstriction and/or decreased prostacyclin-induced vasodilation. Spinotrapezius arcade arterioles from 12-wk-old lean (LZR) and OZR were chosen for microcirculatory observation. Arteriolar diameter (5 LZR ...
Roy Uzzal - - 2005
5,6-trans-AA (5,6-TAA, where TAA stands for trans-arachidonic acid) is a recently identified trans fatty acid that originates from the cis-trans isomerization of AA initiated by the NO2 radical. This trans fatty acid has been detected in blood circulation and we suggested that it functions as a lipid mediator of the ...
Ciccoli Roberto - - 2005
Cyclo-oxygenases-1/2 (COX-1/2) catalyse the oxygenation of AA (arachidonic acid) and related polyunsaturated fatty acids to endoperoxide precursors of prostanoids. COX-1 is referred to as a constitutive enzyme involved in haemostasis, whereas COX-2 is an inducible enzyme expressed in inflammatory diseases and cancer. The fungus Dipodascopsis uninucleata has been shown by ...
Seki Takayuki - - 2005
We examined the effect of N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine) (HET0016), an inhibitor of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) synthesis on the omega-hydroxylation and epoxidation of arachidonic acid (AA) catalyzed by recombinant cytochrome P450 4A1 (CYP4A1), CYP4A2 and CYP4A3, and characterized the enzyme inhibitory profile of HET0016. The IC50 values of HET0016 for recombinant CYP4A1-, CYP4A2- ...
Chávez Ibeth Oviedo - - 2005
Hexane extract from the bark of Amphipterygium adstringens, as well as its principal constituents, masticadienonic acid and 3alpha-hydroxymasticadienolic acid, inhibited the growth of five human cancer cell lines. Derivatives of, namely 24,25 S-dihydromasticadienonic acid and masticadienolic acid, were also evaluated. The results showed that both and had greater activity than ...
Chen Wen-Ying - - 2005
We investigated whether GABA activates phospholipase A2 (PLA2) during acrosomal exocytosis, and if the MEK-ERK1/2 pathway modulates PLA2 activation initiated by GABA, progesterone or zona pellucida (ZP). In guinea pig spermatozoa prelabelled with [14C]arachidonic acid or [14C]choline chloride, GABA stimulated a decrease in phosphatidylcholine (PC), and release of arachidonic acid ...
Dunn Laurel K - - 2005
Shell-less culture of chick chorioallantoic membrane (CAM) of developing chicken embryos is a useful model to evaluate the effects of vascular agents. We assessed the response of CAM vessels to epoxyeicosatrienoic acids (EETs), derivatives of the essential fatty acid arachidonic acid, that have a number of important biological functions, including ...
Miyata Noriyuki - - 2005
Cytochrome P450s (P450) metabolize arachidonic acid (AA) to hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs). Among these eicosanoids, 20-HETE is formed in a tissue and cell-specific fashion and plays an important role in the regulation of vascular tone in the brain, kidney, heart and splanchnic beds. 20-HETE is a potent ...
Estévez Mario - - 2005
The physico-chemical characteristics of a traditional Finnish liver sausage (FLS) and different types of Spanish porcine liver pâtés (commercial, home-made and experimental) were studied. The characteristic recipes and different protocols of manufacture influenced the chemical composition and oxidative stability of the liver products. FLS showed, amongst the liver products, the ...
Kwon Kyoung Ja - - 2005
Arachidonic acid (AA) is released from membrane phospholipids during normal and pathologic processes such as neurodegeneration. AA is metabolized via lipoxygenase (LOX)-, cyclooxygenase (COX)-, and cytochrome P450 (CYP450)-catalyzed pathways. We investigated the relative contributions of these pathways in AA-induced neuronal death. Exposure of cultured cortical neurons to AA (50 microM) ...
Yang Kun-Ta - - 2005
Arachidonic acid (AA) plays important physiological or pathophysiological roles. Here, we show in cultured rat astrocytes that: (i) endothelin-1 or thapsigargin (Tg) induces store-depleted activated Ca(2+) entry (CCE), which is inhibited by 2-aminoethoxydiphenyl borane (2-APB) or La(3+); (ii) AA (10 microM) and other unsaturated fatty acids (8,11,14-eicosatrienoic acid and gamma-linoleic ...
Yaghini Fariborz A - - 2005
Angiotensin II and the arachidonic acid metabolite derived via cytochrome P450 20-hydroxyeicostetraenoic acid promote vasoconstriction and vascular smooth muscle cell (VSMC) proliferation. This study was conducted to determine if 20-hydroxyeicostetraenoic acid contributes to angiotensin II-induced neointimal formation in balloon-injured rat carotid artery. In anesthetized rats, the drugs were infused into ...
Hughes-Fulford Millie - - 2005
For the past 60 years, dietary intake of essential fatty acids has increased. Moreover, the omega-6 fatty acids have recently been found to play an important role in regulation of gene expression. Proliferation of human prostate cells was significantly increased 48 h after arachidonic acid (AA) addition. We have analyzed ...
You Junping - - 2005
We tested the hypotheses that EDHF in rat middle cerebral arteries (MCAs) involves 1) metabolism of arachidonic acid through the epoxygenase pathway, 2) metabolism of arachidonic acid through the lipoxygenase pathway, or 3) reactive oxygen species. EDHF-mediated dilations were elicited in isolated and pressurized rat MCAs by activation of endothelial ...
Baber Syed R - - 2005
Generation of vasoactive prostanoids from arachidonic acid by cyclooxygenase (COX)-1 and COX-2 was investigated in anesthetized mice. Intravenous injections of the prostanoid precursor arachidonic acid increased pulmonary arterial pressure and decreased systemic arterial pressure. Pulmonary pressor and systemic depressor responses were attenuated by SC-560 and nimesulide, inhibitors of COX-1 and ...
López-Lluch G - - 2005
Arachidonic acid metabolism is modulated during differentiation induced by 1alpha,25(OH)(2)D(3) in HL-60 cells. Antioxidants that affect arachidonic acid metabolism enhance this differentiation program. Ascorbate also enhances differentiation in 1alpha,25(OH)(2)D(3)-induced cells depending on the induction of cAMP. The aim of this work was to study if this cAMP rise depends on ...
Serrano-Mollar Anna - - 2005
In recent years, significant progress has been made in understanding the involvement of pro-inflammatory lipidic mediators in the pathogenesis of allergic diseases. The most relevant lipidic mediator is arachidonic acid and its metabolites. Arachidonic acid is the precursor for biosynthesis of eicosanoids, potent mediators of inflammation that have been implicated ...
Maloberti Paula - - 2005
Arachidonic acid and its lypoxygenated metabolites play a fundamental role in the hormonal regulation of steroidogenesis. Reduction in the expression of the mitochondrial acyl-CoA thioesterase (MTE-I) by antisense or small interfering RNA (siRNA) and of the arachidonic acid-preferring acyl-CoA synthetase (ACS4) by siRNA produced a marked reduction in steroid output ...
Harris Robin B - - 2005
Differential effects of fatty acids on carcinogenesis suggest that fatty acid composition is important in tumor development. Arachidonic acid and its metabolites elicit inflammation and promote tumor formation in mouse skin. Inhibitors of the arachidonic cascade inhibit tumor incidence. A population-based case control study in Southeastern Arizona tested the hypothesis ...
Ferrante Judith V - - 2005
The metabolism of arachidonic acid via the lipoxygenase and cyclooxygenase pathways generates metabolites that regulate the inflammatory response. Although products of lipoxygenase are classically proinflammatory, recently it has been demonstrated that lipoxins, 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and 15-hydroxyeicosatetraenoic acid exhibit anti-inflammatory activity. We now demonstrate for the first time that 15-HPETE ...
Lundblad Mia Sandberg - - 2005
Arachidonic acid is oxidized by cytochromes P450 2C (CYP2C) to epoxyeicosatrienoic acids (EETs), possessing vasoactive properties, with 11,12-EET as the endothelium derived hyperpolarization factor. Genetic variants of CYP2C enzymes have altered drug metabolizing capacity. Our primary aim was to determine whether EET biosynthesis differed in human liver microsomes with known ...
Yang Wenqi - - 2005
5,6-epoxyeicosatrienoic acid (5,6-EET) is a cytochrome P450 epoxygenase metabolite of arachidonic acid that causes vasorelaxation. However, investigations of its role in biological systems have been limited by its chemical instability. We developed a stable agonist of 5,6-EET, 5-(pentadeca-3(Z),6(Z),9(Z)-trienyloxy)pentanoic acid (PTPA), in which the 5,6-epoxide was replaced with a 5-ether. PTPA ...
880-01 Kun-Ta, Yang
Thesis (Ph.D.)--National Taiwan University Graduate Institute of Physiology
Kroetz Deanna L - - 2005
Cytochrome P450-catalyzed metabolism of arachidonic acid is an important pathway for the formation of paracrine and autocrine mediators of numerous biological effects. The omega-hydroxylation of arachidonic acid generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in numerous tissues, particularly the vasculature and kidney tubules. Members of the cytochrome P450 4A and ...
Gainer James V - - 2005
BACKGROUND: The CYP4A11 arachidonic acid monooxygenase oxidizes endogenous arachidonic acid (AA) to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite with renovascular and tubular functions. Mice with targeted disruption of Cyp4a14, a murine homologue of CYP4A11, have severe hypertension. We combined molecular and biochemical approaches to identify a functional variant of the CYP4A11 ...
Yi Sun-Ju - - 2004
We have investigated whether arachidonic acid could regulate tissue transglutaminase (tTGase) via intracellular reactive oxygen species (ROS) in NIH3T3 cells. tTGase was identified in NIH3T3 cells by Western blot and confocal microscopy. Arachidonic acid elevated in situ tTGase activity in dose- and time-dependent manners with a maximal level at 1h, ...
Senger Toralf - - 2005
A complex mixture of fatty acid-derived aldehydes, ketones, and alcohols is released upon wounding of the moss Physcomitrella patens. To investigate the formation of these oxylipins at the molecular level we isolated a lipoxygenase from P. patens, which was identified in an EST library by sequence homology to lipoxygenases from ...
Wei Yuan - - 2004
We used the patch-clamp technique to study the effect of arachidonic acid (AA) on epithelial Na channels (ENaC) in the rat cortical collecting duct (CCD). Application of 10 microM AA decreased the ENaC activity defined by NPo from 1.0 to 0.1. The dose-response curve of the AA effect on ENaC ...
Kowluru Anjaneyulu - - 2004
Long-chain fatty acids (e.g. arachidonic acid) have been implicated in physiological control of insulin secretion. We previously reported histidine phosphorylation of at least two islet proteins (e.g., NDP kinase and the beta subunit of trimeric G-proteins), and suggested that such a signalling step may have regulatory roles in beta cell ...
Buckler K J - - 2005
TREK-1 is a member of the two-pore domain potassium (K(2P)) channel family that is mechano-, heat, pH, voltage and lipid sensitive. It is highly expressed in the central nervous system and probably encodes one of the previously described arachidonic acid-activated K(+) channels. Polyunsaturated fatty acids and lysophospholipids protect the brain ...
Caley Alex J - - 2005
Two-pore-domain potassium channels are a family of ion channels that are widely believed to play an important role in maintaining and regulating neuronal excitability. It has been shown that they can be modulated by an extraordinarily diverse range of endogenous and exogenous factors. One particular member of the family, TREK-1 ...
Zhang David X - - 2005
We recently reported that the lipoxygenase product 11,12,15-trihydroxyeicosatrienoic acid (THETA) mediates arachidonic acid (AA)-induced relaxation in the rabbit aorta. This study was designed to determine whether this lipoxygenase metabolite is involved in relaxation responses to AA in rabbit small mesenteric arteries. AA (10(-9)-10(-4) M) produced potent relaxations in isolated phenylephrine-preconstricted ...
Levine Lawrence - - 2004
I have postulated that arachidonic acid release from rat liver cells is associated with cancer chemoprevention. Since it has been reported that inhibition of proteasome activities may prevent cancer, the effects of proteasome inhibitors on arachidonic acid release from cells and on prostaglandin I2 production in rat liver cells were ...
Fang Xiang - - 2004
We investigated the effects of soluble epoxide hydrolase (sEH) inhibition on epoxyeicosatrienoic acid (EET) metabolism in intact human blood vessels, including the human saphenous vein (HSV), coronary artery (HCA), and aorta (HA). When HSV segments were perfused with 2 micromol/l 14,15-[3H]EET for 4 h, >60% of radioactivity in the perfusion ...
Zhang David X - - 2004
The present study characterizes the vascular responses of isolated small bovine adrenal cortical arteries to acetylcholine, an endogenous neurotransmitter in the adrenal gland. Acetylcholine (10(-10) to 10(-6) m) elicited a concentration-dependent relaxation, with a maximal relaxation of 96 +/- 1% and EC50 of 4.2 nm. The relaxation was abolished by ...
Saitoh Hiroto - - 2004
An excised patch membrane sensor for arachidonic acid (AA) is described, whose response stems from AA-induced channel-type transport of ions across the excised patch membrane. The patch membrane sensor was prepared in situ by excising mouse hippocampal cell membranes with patch pipets having a tip diameter of < 0.5 microm. ...
DeBarber Andrea E - - 2004
Studies have shown that mammalian cytochromes p450 participate in the metabolism of terpenes, yet their role in the biotransformation of farnesol, an endogenous 15-carbon isoprenol, is unknown. In this report, [(14)C]-farnesol was transformed to more polar metabolites by NADPH-supplemented mammalian microsomes. In experiments with microsomes isolated from acetone-treated animals, the ...
Tanabe Michiharu - - 2004
The current study assessed the differential incorporation of 12-hydroperoxyeicosatetraenoic acid (12-HPETE), arachidonic acid (AA), 12-hydroxyeicosatetraenoic acid (12-HETE) and the linoleic acid (LA) oxidation products, 13-hydroxyoctadecadienoic acid (13-HODE) and 13-hydroperoxyoctadecadienoic acid (13-HPODE), into human umbilical vein endothelial cells (HUVEC). Approximately 80-90% of AA (10(-8)-10(-5)M) and 80% of LA (10(-8)-10(-5)M) were incorporated ...
Tirapelli Carlos R - - 2004
The present work describes the mechanisms involved in the vasorelaxant effect of the diterpene ent-kaur-16-en-19-oic acid (kaurenoic acid). Kaurenoic acid (10, 50 and 100 microM) concentration-dependently inhibited phenylephrine and KCl-induced contraction in either endothelium-intact or -denuded rat aortic rings. Kaurenoic acid also reduced CaCl(2)-induced contraction in Ca(2+)-free solution containing KCl ...
Le Quéré Valérie - - 2004
CYP4F isoforms are involved in the oxidation of important cellular mediators such as leukotriene B4 (LTB4) and prostaglandins. The proinflammatory agent LTB4 and cytotoxic leukotoxins have been associated with several inflammatory diseases. We present evidence that the hydroxylation of Z 9(10)-epoxyoctadecanoic, Z 9(10)-epoxyoctadec-Z 12-enoic, and Z 12(13)-epoxyoctadec-Z 9-enoic acids and ...
Amemiya Tsugio - - 2004
PURPOSE: The purpose of this study was to demonstrate fatty acids in the rat retina and to show that time-of-flight secondary ion mass spectrometry (TOF-SIMS) can replace histochemistry. METHODS: Five normal 3-month-old Wistar Kyoto rats were used. The eyes were enucleated under pentobarbital anesthesia, immediately put into liquid nitrogen without ...
Garcia Eloi S - - 2004
Hemocoelic inoculation of epimastigotes of Trypanosoma rangeli strain H14 into 5th-instar larvae of Rhodnius prolixus previously fed on blood containing the same parasites, showed reduced number of hemocyte microaggregates in the hemolymph, enhanced number of flagellates in the hemolymph as well as increased mortality of these insects. All these effects ...
Cui Xiaoxuan - - 2004
OBJECTIVE: Sepsis is characterized by an early, hyperdynamic phase and a late, hypodynamic phase. Although studies have shown that cytochrome P450 (CYP) plays an important role in the regulation of vascular reactivity, alterations of vascular CYP isoforms in sepsis remain unknown. Since CYP2C11 and CYP2J4 convert arachidonic acid to vasodilative ...
DeLozier Tracy C - - 2004
The human CYP2Cs have been studied extensively with respect to the metabolism of clinically important drugs and endogenous chemicals such as arachidonic acid (AA). Five members of the mouse CYP2C family have previously been described that metabolize arachidonic acid into regio- and stereospecific epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids, which ...
Sarkis Albert - - 2004
PURPOSE OF REVIEW: Cytochrome P-450 metabolites of arachidonic acid have been reported to play an important role in the control of renal function and vascular tone, and in the long-term control of arterial pressure. In this regard, 20-hydroxyeicosatetraenoic acid is a potent vasoconstrictor that inhibits sodium reabsorption in the kidney. ...
McCowen Karen C - - 2004
Despite absence of essential fatty acid deficiency (EFAD), increases in arachidonic acid to linoleic acid ratios occur in serum phospholipid of patients treated with chronic total parenteral nutrition (TPN). The parenteral lipid component of TPN contains abundant linoleate; thus low phospholipid linoleate may reflect increased conversion to arachidonate. Arachidonic acid ...
Roy Uzzal - - 2004
Trans-arachidonic acids (trans-AA) are products of cis-trans isomerization of arachidonic acid by nitrogen dioxide radical (NO(2)), and occur in vivo, but their metabolism is unknown. We found that hepatic microsomes oxidized trans-AA via cytochrome P450/NADPH system to epoxides, which were hydrolyzed by epoxide hydrolase to diols (DiHETEs). 14,15-trans-AA produced one ...
Vance Russell E RE Department of Microbiology and Molecular Genetics, Center for Genomic Applications and Therapeutics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, - - 2004
In mammals, lipoxygenases play key roles in inflammation by initiating the transformation of arachidonic acid into potent bioactive lipid mediators such as leukotrienes and lipoxins. In general, most bacteria are believed to lack lipoxygenases and their polyunsaturated fatty acid substrates. It is therefore of interest that an ORF (PA1169) with ...
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