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1.
环氧化酶-2（COX-2）因参与机体的多种病理生理过程而日益受到重视。它在眼部炎症、角膜和视网膜新生血管、青光眼、白内障、增生性玻璃体视网膜病变等许多疾病的发生发展中起着重要的介质作用。自20世纪90年代初,国外就发现环氧化酶有两种同工酶COX-1和COX-2,COX-1参与机体正常的生理功能,而COX-2则参与多种病理生理过程,包括炎症、损伤、修复、新生血管的生成及肿瘤的生长和转移,对COX-2的研究更有助于探究犬的某些眼部疾病的发生机制以及进一步完善疾病治疗手段,提高治疗效果。本文就环氧化酶-2与犬眼部疾病的关系进行论述。 相似文献
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Karsak M Gaffal E Date R Wang-Eckhardt L Rehnelt J Petrosino S Starowicz K Steuder R Schlicker E Cravatt B Mechoulam R Buettner R Werner S Di Marzo V Tüting T Zimmer A 《Science (New York, N.Y.)》2007,316(5830):1494-1497
Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity, we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase-deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated allergic inflammation, whereas receptor agonists attenuated inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin and suggest a target for therapeutic intervention. 相似文献
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Berghuis P Rajnicek AM Morozov YM Ross RA Mulder J Urbán GM Monory K Marsicano G Matteoli M Canty A Irving AJ Katona I Yanagawa Y Rakic P Lutz B Mackie K Harkany T 《Science (New York, N.Y.)》2007,316(5828):1212-1216
The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB(1) cannabinoid receptors (CB(1)Rs) are enriched in the axonal growth cones of gamma-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB(1)R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB(1)Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo. 相似文献
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Prostaglandins E1 and E2 antagonize norepinephrine effects on cerebellar purkinje cells: microelectrophoretic study 总被引：2，自引：0，他引：2
In microelectrophoretic experiments, prostaglandins E(1) and E(2) antagonize the reduction in discharge rate of cerebellar Purkinje cells produced by norepinephrine. Slowing of discharge evoked by 3',5'-adenosine monophosphate or gamma aminobutyric acid is not antagonized. These data provide the first indication that endogenous prostaglandins may physiologically function to modulate central noradrenergic junctions. 相似文献
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Identification and functional characterization of brainstem cannabinoid CB2 receptors 总被引：1，自引：0，他引：1
Van Sickle MD Duncan M Kingsley PJ Mouihate A Urbani P Mackie K Stella N Makriyannis A Piomelli D Davison JS Marnett LJ Di Marzo V Pittman QJ Patel KD Sharkey KA 《Science (New York, N.Y.)》2005,310(5746):329-332
The presence and function of CB2 receptors in central nervous system (CNS) neurons are controversial. We report the expression of CB2 receptor messenger RNA and protein localization on brainstem neurons. These functional CB2 receptors in the brainstem were activated by a CB2 receptor agonist, 2-arachidonoylglycerol, and by elevated endogenous levels of endocannabinoids, which also act at CB1 receptors. CB2 receptors represent an alternative site of action of endocannabinoids that opens the possibility of nonpsychotropic therapeutic interventions using enhanced endocannabinoid levels in localized brain areas. 相似文献
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Development of irreversible platelet aggregation and the accompanying release of platelet-bound serotonin and production of prostaglandins is suppressed by 5,8,11,14-eicosatetraynoic acid (TYA). These findings may be explained by an ability of TYA to inhibit the enzymatic conversion of arachidonate to a newly recognized factor, labile aggregation-stimulating substance, which induces platelet aggregation, and to prostaglandins E(2) and F(2alpha). 相似文献
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L Shenkman Y Imai K Kataoka C S Hollander L Wan S C Tang T AvRuskin 《Science (New York, N.Y.)》1974,184(132):81-82
Intravaginal or intravenous administration of prostaglandin F(2alpha) to pregnant women produced significant elevations of plasma triiodothyronine and thyroxine concentrations, but no rise of thyrotropin. These observations are consistent with those of previous in vitro studies indicating that prostaglandins can act directly on the thyroid gland to stimulate thyroid hormone synthesis or release, or both. 相似文献
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为研究内毒素(Endotoxin,ET)对体外培养的仓鼠肾细胞膜活性影响及阳离子A(Cation A,CA)对其的保护效应。随机将体外培养的仓鼠肾细胞(BHK-21)分为:对照组(Ⅰ组)、ET处理组(Ⅱ组)和ET+CA组(Ⅲ组),采用微量滴定法和定磷法,第3、6、12、24小时测定细胞膜上磷脂酶A2(PLA2)和ATP酶(ATPase)的活性。结果表明,II组中PLA2活性在整个实验过程中均显著高于I组(P<0.01或P<0.05),Na+-K+-ATPase、Ca2+-Mg2+-ATPase活性呈现先增高后降低的趋势(3、6、12 h增高,24 h以后降低)。III组与II组相比,PLA2的活性显著降低(P<0.05),Na+-K+-ATPase、Ca2+-Mg2+-ATPase活性在整个实验过程中均显著增高(P<0.01或P<0.05)。细胞膜上的PLA2活性增高,ATPase的活性先增高后降低,提示细胞膜受到损伤;CA能明显改善内毒素所致的体外细胞膜损伤。 相似文献
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Hino T Matsumoto Y Nagano S Sugimoto H Fukumori Y Murata T Iwata S Shiro Y 《Science (New York, N.Y.)》2010,330(6011):1666-1670
Nitric oxide reductase (NOR) is an iron-containing enzyme that catalyzes the reduction of nitric oxide (NO) to generate a major greenhouse gas, nitrous oxide (N(2)O). Here, we report the crystal structure of NOR from Pseudomonas aeruginosa at 2.7 angstrom resolution. The structure reveals details of the catalytic binuclear center. The non-heme iron (Fe(B)) is coordinated by three His and one Glu ligands, but a His-Tyr covalent linkage common in cytochrome oxidases (COX) is absent. This structural characteristic is crucial for NOR reaction. Although the overall structure of NOR is closely related to COX, neither the D- nor K-proton pathway, which connect the COX active center to the intracellular space, was observed. Protons required for the NOR reaction are probably provided from the extracellular side. 相似文献
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Ras-GAP (GTPase activating protein) is a regulatory protein that stimulates the intrinsic guanosine triphosphatase (GTPase) activity of the proto-oncogene product p21ras. A domain of the neurofibromatosis gene product (NF1) that has sequence similarity to the catalytic domain of Ras-GAP and to yeast IRA gene products also has a specific stimulatory activity toward p21ras GTPase. Arachidonic acid and phosphatidic acid inactivate GAP, but no agents have been identified that stimulate GAP and thereby switch p21ras off. With the use of recombinant Ha-c-Ras and Ras-GAP, NF1, and GAP catalytic domains, it was found that prostaglandins PGF2 alpha and PGA2 stimulated Ras-GAP and that prostacyclin PGI2 inhibited Ras-GAP. The stimulatory effect of PGF2 alpha was saturable and structure-specific and competed with the inhibitory effect of arachidonic acid. Arachidonic acid also inhibited the catalytic activity of NF1, but prostaglandins were not stimulatory. These results suggest a mechanism for the allosteric control of Ras function through the modulation of arachidonate metabolism. 相似文献
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Structures of free and inhibited human secretory phospholipase A2 from inflammatory exudate 总被引：5，自引：0，他引：5
D L Scott S P White J L Browning J J Rosa M H Gelb P B Sigler 《Science (New York, N.Y.)》1991,254(5034):1007-1010
Phospholipase A2 (PLA2) participates in a wide range of cellular processes including inflammation and transmembrane signaling. A human nonpancreatic secretory PLA2 (hnps-PLA2) has been identified that is found in high concentrations in the synovial fluid of patients with rheumatoid arthritis and in the plasma of patients with septic shock. This enzyme is secreted from certain cell types in response to the proinflammatory cytokines, tumor necrosis factor or interleukin-1. The crystal structures of the calcium-bound form of this enzyme have been determined at physiological pH both in the presence [2.1 angstrom (A) resolution] and absence (2.2 A resolution) of a transition-state analogue. Although the critical features that suggest the chemistry of catalysis are identical to those inferred from the crystal structures of other extracellular PLA2s, the shape of the hydrophobic channel of hnps-PLA2 is uniquely modulated by substrate binding. 相似文献
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Homogenates of rat cerebral cortex contain material corresponding to prostaglandins E(1), E(2), F(1)alpha, and F(2)alpha which are concentrated mainly in the light microsomal and mitochondrial fractions. Only the former fraction exhibits significant ability to synthesize prostaglandins E(1) and F(1)alpha from bis-homo-gamma-linolenic acid. After subfractionation of the crude mitochondrial fraction, prostaglandin E and F material is found mainly in the cholinergic and noncholinergic nerve endings. We conclude that the nerve endings are a storage site, whereas the light microsomes are the site of synthesis. 相似文献
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Interfacial catalysis: the mechanism of phospholipase A2 总被引：16，自引：0，他引：16
D L Scott S P White Z Otwinowski W Yuan M H Gelb P B Sigler 《Science (New York, N.Y.)》1990,250(4987):1541-1546
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Electrical activity in neurons is generally initiated in dendritic processes then propagated along axons to synapses, where it is passed to other neurons. Major structural features of neurons-their dendrites and axons-are thus related to their fundamental functions: the receipt and transmission of information. The acquisition of these distinct properties by dendrites and axons, called polarization, is a critical step in neuronal differentiation. We show here that SAD-A and SAD-B, mammalian orthologs of a kinase needed for presynaptic differentiation in Caenorhabditis elegans, are required for neuronal polarization. These kinases will provide entry points for unraveling signaling mechanisms that polarize neurons. 相似文献
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Prostaglandin involvement in hypothalamic control of gonadotropin and prolactin release 总被引：1，自引：0，他引：1
Prostaglandin E(2) (PGE(2)) injected into the third ventricle of ovariectomized rats increased plasma luteinizing hormone dramatically and follicle stimulating hormone slightly. PGE(1) elevated prolactin; PGF(1alpha) or PGF(2alpha) had no effect. PGE(2) or PGE(1) injected directly into the anterior pituitary were ineffective. These results suggest that specific prostaglandins act at the hypothalamus to control pituitary hormone release. 相似文献
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Crystal structure of bee-venom phospholipase A2 in a complex with a transition-state analogue 总被引：6，自引：0，他引：6
The 2.0 angstroms crystal structure of a complex containing bee-venom phospholipase A2 (PLA2) and a phosphonate transition-state analogue was solved by multiple isomorphous replacement. The electron-density map is sufficiently detailed to visualize the proximal sugars of the enzyme's N-linked carbohydrate and a single molecule of the transition-state analogue bound ot its active center. Although bee-venom PLA2 does not belong to the large homologous Class I/II family that encompasses most other well-studied PLA2s, there is segmental sequence similarity and conservation of many functional substructures. Comparison of the bee-venom enzyme with other phospholipase structures provides compelling evidence for a common catalytic mechanism. 相似文献
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Berkefeld H Sailer CA Bildl W Rohde V Thumfart JO Eble S Klugbauer N Reisinger E Bischofberger J Oliver D Knaus HG Schulte U Fakler B 《Science (New York, N.Y.)》2006,314(5799):615-620
Large-conductance calcium- and voltage-activated potassium channels (BKCa) are dually activated by membrane depolarization and elevation of cytosolic calcium ions (Ca2+). Under normal cellular conditions, BKCa channel activation requires Ca2+ concentrations that typically occur in close proximity to Ca2+ sources. We show that BKCa channels affinity-purified from rat brain are assembled into macromolecular complexes with the voltage-gated calcium channels Cav1.2 (L-type), Cav2.1 (P/Q-type), and Cav2.2 (N-type). Heterologously expressed BKCa-Cav complexes reconstitute a functional "Ca2+ nanodomain" where Ca2+ influx through the Cav channel activates BKCa in the physiological voltage range with submillisecond kinetics. Complex formation with distinct Cav channels enables BKCa-mediated membrane hyperpolarization that controls neuronal firing pattern and release of hormones and transmitters in the central nervous system. 相似文献
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东北地区农田主要杂草的病原真菌及其地理分布 总被引：1，自引：0，他引：1
报道了东北地区农田主要杂草上的病原真菌19属41种,寄生在14个科26个属的寄主植物上。其中新种1个：问荆柱盘孢（Cylindrosporium equiseti Liu et Bai）;东北地区首次报道种5个。对每个种列出学名、寄主、生境和分布,所有标本保藏在解放军军需大学真菌标本室。 相似文献
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【目的】研究湖羊卵巢组织COX2、HAS2、TSG6和PTX3的mRNA表达水平与湖羊繁殖性能的相关性,筛选影响湖羊高产的候选基因,为揭示湖羊高繁多胎分子遗传机理提供依据。【方法】选取16只经产湖羊母羊,分为低产组和高产组,于发情后24—36 h屠宰,应用RT-PCR技术检测COX2、HAS2、TSG6和PTX3的组织表达特征,进一步利用实时荧光定量PCR技术分析各基因mRNA在低产组和高产组湖羊卵巢组织中的表达差异。【结果】COX2、HAS2、TSG6和PTX3均在湖羊卵巢组织中表达,在卵巢组织,高产组TSG6和PTX3的mRNA表达极显著高于低产组(P＜0.01),低产组HAS2的mRNA表达极显著高于高产组(P＜0.01),而COX2的mRNA表达在高产组和低产组间无显著差异(P＞0.05)。【结论】HAS2、TSG6和PTX3的mRNA表达在高产组和低产组间差异极显著,可能与湖羊繁殖性能相关,可作为影响湖羊高产的候选基因。 相似文献