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排序方式: 共有375条查询结果,搜索用时 156 毫秒
91.
Leigh A. Jania Subhashini Chandrasekharan Michael G. Backlund Nicholas A. Foley John Snouwaert I-Ming Wang Patsy Clark Laurent P. Audoly Beverly H. Koller 《Prostaglandins & other lipid mediators》2009,88(3-4):73-81
Prostaglandin E2 (PGE2) plays an important role in the normal physiology of many organ systems. Increased levels of this lipid mediator are associated with many disease states, and it potently regulates inflammatory responses. Three enzymes capable of in vitro synthesis of PGE2 from the cyclooxygenase metabolite PGH2 have been described. Here, we examine the contribution of one of these enzymes to PGE2 production, mPges-2, which encodes microsomal prostaglandin synthase-2 (mPGES-2), by generating mice homozygous for the null allele of this gene. Loss of mPges-2 expression did not result in a measurable decrease in PGE2 levels in any tissue or cell type examined from healthy mice. Taken together, analysis of the mPGES-2 deficient mouse lines does not substantiate the contention that mPGES-2 is a PGE2 synthase. 相似文献
92.
Adenosine has profound depressant effects upon the electrophysiological activity of the brain, but the adenosine receptor subtypes which mediate these responses are uncertain. In order to resolve this question, we have characterized the effects of two adenosine analogs which differ in their relative potencies at adenosine A1 and A2 receptors. The effects of these adenosine analogs were examined on spontaneous firing rate of Purkinje neurons in the rat cerebellum in situ, in cerebellar brain slices in vitro, and on synaptic transmission in the rat hippocampus in vitro. Although the A2 agonist appeared to be more potent with local drug application techniques in situ, our in vitro results suggest that the A1 receptor subtype is involved in the electrophysiological actions of these drugs in both rat cerebellum and hippocampus. Furthermore, these data indicate that the physical properties of some adenosine analogs may reduce apparent drug potencies when they are studied with local application techniques. 相似文献
93.
94.
Non-ribosomal nucleolar proteins in HeLa cells 总被引:1,自引:0,他引:1
The study of nucleolar macromolecular components has previously emphasized ribosomal precursor and mature RNA, or ribosomal structural proteins. In this work, we have stressed the purification of nucleoli, and have studied their protein composition. The results indicate that there exists in highly purified nucleoli of HeLa cells, a class of high molecular weight polypeptides which have been identified by means of size, kinetics of turnover, and metabolic behavior to be non-ribosomal nucleolar-specific proteins. The possibility that these proteins play a part in the assembly of mature ribosomes is discussed. 相似文献
95.
Nucleic acid synthesis in nurse cells of Rhynchosciara angelae Nonato and Pavan, 1951 总被引:1,自引:0,他引:1
R Basile 《Genetics》1969,61(1):Suppl:261-Suppl:273
96.
Xavier Heiligenstein Nicolas Goudin Mickaël M. Ménager Maryse Romao Marjorie Côte Nizar Mahlaoui Alain Fischer Graça Raposo Geneviève de Saint Basile 《Traffic (Copenhagen, Denmark)》2015,16(2):191-203
Chediak–Higashi syndrome (CHS) is caused by mutations in the gene encoding LYST protein, the function of which remains poorly understood. Prominent features of CHS include defective secretory lysosome exocytosis and the presence of enlarged, lysosome‐like organelles in several cell types. In order to get further insight into the role of LYST in the biogenesis and exocytosis of cytotoxic granules, we analyzed cytotoxic T lymphocytes (CTLs) from patients with CHS. Using confocal microscopy and correlative light electron microscopy, we showed that the enlarged organelle in CTLs is a hybrid compartment that contains proteins components from recycling‐late endosomes and lysosomes. Enlargement of cytotoxic granules results from the progressive clustering and then fusion of normal‐sized endolysosomal organelles. At the immunological synapse (IS) in CHS CTLs, cytotoxic granules have limited motility and appear docked while nevertheless unable to degranulate. By increasing the expression of effectors of lytic granule exocytosis, such as Munc13‐4, Rab27a and Slp3, in CHS CTLs, we were able to restore the dynamics and the secretory ability of cytotoxic granules at the IS. Our results indicate that LYST is involved in the trafficking of the effectors involved in exocytosis required for the terminal maturation of perforin‐containing vesicles into secretory cytotoxic granules. 相似文献
97.
98.
Basile M Lin R Kabbani N Karpa K Kilimann M Simpson I Kester M 《Archives of biochemistry and biophysics》2006,446(1):60-68
Paralemmin is a novel lipid-anchored protein, which is highly expressed in neuronal plasma membranes. In this study, we demonstrate that paralemmin specifically interacts with the third intracellular loop of the D3 dopamine receptor. Utilizing co-immunoprecipitation and glutathione-S-transferase (GST) pulldown strategies, we demonstrate that paralemmin interacts exclusively with D3, but not D2 or D4 dopamine receptors or beta-adrenergic receptors. Immunocytochemistry demonstrated co-localization of paralemmin and D3 receptor in vivo in hippocampus and cerebellum and in vitro in glial and neuronal cultures. Deletion mutational analysis indicates that amino acids 154-230 of paralemmin strongly interacted with amino acids 211-227 and 281-330 of the third intracellular loop of D3 receptor. The consequences of these interactions were investigated by co-expression in HEK293 cells. Cell surface biotinylation experiments demonstrate that paralemmin decreased D3 receptor concentration at the plasma membrane. Consistent with this observation, paralemmin expression decreased dopamine-stimulated adenylate cyclase activity. However, paralemmin also decreased basal, isoproterenol and forskolin-stimulated adenylate cyclase activity, suggesting a more general cellular function for paralemmin. Taken together, paralemmin has been implicated as a potent modulator of cellular cAMP signaling within the brain. 相似文献
99.
McClure KF Letavic MA Kalgutkar AS Gabel CA Audoly L Barberia JT Braganza JF Carter D Carty TJ Cortina SR Dombroski MA Donahue KM Elliott NC Gibbons CP Jordan CK Kuperman AV Labasi JM Laliberte RE McCoy JM Naiman BM Nelson KL Nguyen HT Peese KM Sweeney FJ Taylor TJ Trebino CE Abramov YA Laird ER Volberg WA Zhou J Bach J Lombardo F 《Bioorganic & medicinal chemistry letters》2006,16(16):4339-4344
The synthesis, structure-activity relationship, in vivo activity, and metabolic profile for a series of triazolopyridine-oxazole based p38 inhibitors are described. The deficiencies of the lead structure in the series, CP-808844, were overcome by changes to the C4 aryl group and the triazole side-chain culminating in the identification of several potential clinical candidates. 相似文献
100.
Nicoletta Bodrato Luisa Franco Chiara Fresia Lucrezia Guida Cesare Usai Annalisa Salis Iliana Moreschi Chiara Ferraris Claudia Verderio Giovanna Basile Santina Bruzzone Sonia Scarf�� Antonio De Flora Elena Zocchi 《The Journal of biological chemistry》2009,284(22):14777-14787
Abscisic acid (ABA) is a phytohormone regulating important functions in
higher plants, notably responses to abiotic stress. Recently, chemical or
physical stimulation of human granulocytes was shown to induce production and
release of endogenous ABA, which activates specific cell functions. Here we
provide evidence that ABA stimulates several functional activities of the
murine microglial cell line N9 (NO and tumor necrosis factor-α
production, cell migration) through the second messenger cyclic ADP-ribose and
an increase of intracellular calcium. ABA production and release occur in N9
cells stimulated with bacterial lipopolysaccharide, phorbol myristate acetate,
the chemoattractant peptide f-MLP, or β-amyloid, the primary plaque
component in Alzheimer disease. Finally, ABA priming stimulates N9 cell
migration toward β-amyloid. These results indicate that ABA is a
pro-inflammatory hormone inducing autocrine microglial activation, potentially
representing a new target for anti-inflammatory therapies aimed at limiting
microglia-induced tissue damage in the central nervous system.Microglial cells are the monocyte/macrophage equivalent of the central
nervous system and represent the first line of defense in the brain, by
removing infectious agents and damaged cells
(1). Microglia can also release
a variety of trophic factors and cytokines able to regulate the communication
between neuronal and other glial cells and can contribute to tissue repair and
neuroprotection
(2–4).
Pathologic microglial activation, however, confers neurotoxic properties to
these cells, thereby causing neuronal degeneration
(5). Excessive activation of
microglia, under conditions of chronic inflammation, can contribute to the
pathogenesis of neurodegenerative diseases, such as multiple sclerosis and
Alzheimer and Parkinson diseases, by producing and releasing a number of
potentially cytotoxic substances, including pro-inflammatory cytokines and NO
(4,
6–8).
Therefore, identification of the molecular mechanisms underlying microglial
activation might lead to the development of new anti-inflammatory drugs for
the treatment of these diseases.Abscisic acid
(ABA)2 is a plant
hormone regulating important biological functions in higher plants, including
response to abiotic stress, control of stomatal closure, regulation of seed
dormancy, and germination (9).
Recently, ABA was shown to behave as an endogenous pro-inflammatory hormone in
human granulocytes (10),
stimulating several functional activities of these cells (migration,
phagocytosis, reactive oxygen species, and NO production) through a signaling
cascade that involves a protein kinase A-mediated ADP-ribosyl cyclase
phosphorylation and consequent overproduction of the universal Ca2+
mobilizer cyclic ADP-ribose (cADPR)
(11). This mechanism leads to
an increase of the intracellular Ca2+ concentration, which is
ultimately responsible for granulocyte activation
(10).The facts that microglial cells play a defensive role in the central
nervous system similar to that of granulocytes in other tissues and that cADPR
has been described as the second messenger involved in the activation of
microglia induced by lipopolysaccharide (LPS)
(12) prompted us to
investigate the effect of ABA in these cells.Indeed, exogenous ABA, at concentrations ranging from 250 nm to
20 μm, elicits functional activation of murine N9 cells,
stimulating TNF-α release and cell migration through activation of the
ADP-ribosyl cyclase CD38 and overproduction of cADPR. Moreover, N9 cells
produce and release ABA when stimulated with LPS, amyloid β-peptide
(βA), phorbol myristate acetate (PMA), or the chemoattractant peptide
f-MLP. These results indicate that ABA behaves as an endogenous,
pro-inflammatory hormone in murine microglia and provide a new target for
future investigations into the role of this hormone in inflammatory and
degenerative diseases of the central nervous system accompanied by microglial
activation. 相似文献