排序方式: 共有43条查询结果,搜索用时 189 毫秒
1.
V Macchia A Rocino E Gulletta E Consiglio S Varrone 《Comptes rendus des séances de la Société de biologie et de ses filiales》1978,172(5):860-867
Guanylate cyclase activity is present in crude E. coli extract. Guanylate cyclase has been purified 3500 fold from this extract, through ammonium sulfate fractionation, DEAE-cellulose chromatography. Sephadex G-75 gel-filtration and polyacrylamide gel preparative microelectrophoresis. During the purification a guanylate cyclase inhibitor has been separated. 相似文献
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Feliciello A Cardone L Garbi C Ginsberg MD Varrone S Rubin CS Avvedimento EV Gottesman ME 《FEBS letters》1999,464(3):174-178
A yeast two-hybrid screen revealed that regulatory subunits (RII) of PKAII bind the Yotiao protein. Yotiao interacts with the NR1 subunit of the NMDA receptor. A purified C-terminal fragment of Yotiao binds PKAII, via an RII binding site constituted by amino acid residues 1452-1469, with a dissociation constant (K(d)) between 50 and 90 nM in vitro. A stable complex composed of Yotiao, RII and NR1 was immunoprecipitated from whole rat brain extracts. Immunostaining analysis disclosed that Yotiao, RIIbeta and NR1 colocalize in striatal and cerebellar neurons. Co-assembly of Yotiao/PKAII complexes with NR1 subunits may promote cAMP-dependent modulation of NMDA receptor activity at synapses, thereby influencing brain development and synaptic plasticity. 相似文献
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T de Cristofaro A Affaitati L Cariello E V Avvedimento S Varrone 《Biochemical and biophysical research communications》1999,260(1):150-158
A common feature of CAG-expansion neurodegenerative diseases is the presence of intranuclear aggregates in neuronal cells. We have used a synthetic fusion protein containing at the NH2 terminus the influenza hemoagglutinin epitope (HA), a polyglutamine stretch (polyQ) of various size (17, 36, 43 CAG) and a COOH tail encoding the green fluorescent protein (GFP). The fusion proteins were expressed in COS-7 and neuroblastoma SK-N-BE cells. We found that the formation of aggregates largely depends on the length of polyglutamine tracts and on the levels of expression of the fusion protein. Moreover, transglutaminase overexpression caused an increase of insoluble aggregates only in cells expressing the mutant expanded protein. Conversely, treatment of cells with cystamine, a transglutaminase inhibitor, reduced the percentage of aggregates. We found also that the inhibition of the proteasome ubiquitin-dependent degradation increased the formation of intranuclear aggregates. These data suggest that length of polyglutamine tract, its expression, unbalance between cellular transglutaminase activity, and the ubiquitin-degradation pathway are key factors in the formation of intranuclear aggregates. 相似文献
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Affaitati A Cardone L de Cristofaro T Carlucci A Ginsberg MD Varrone S Gottesman ME Avvedimento EV Feliciello A 《The Journal of biological chemistry》2003,278(6):4286-4294
A-Kinase anchor proteins (AKAPs) immobilize and concentrate protein kinase A (PKA) isoforms at specific subcellular compartments. Intracellular targeting of PKA holoenzyme elicits rapid and efficient phosphorylation of target proteins, thereby increasing sensitivity of downstream effectors to cAMP action. AKAP121 targets PKA to the cytoplasmic surface of mitochondria. Here we show that conditional expression of AKAP121 in PC12 cells selectively enhances cAMP.PKA signaling to mitochondria. AKAP121 induction stimulates PKA-dependent phosphorylation of the proapoptotic protein BAD at Ser(155), inhibits release of cytochrome c from mitochondria, and protects cells from apoptosis. An AKAP121 derivative mutant that localizes on mitochondria but does not bind PKA down-regulates PKA signaling to the mitochondria and promotes apoptosis. These findings indicate that PKA anchored by AKAP121 transduces cAMP signals to the mitochondria, and it may play an important role in mitochondrial physiology. 相似文献
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Renan Idalencio Fabiana Kalichak Jo?o Gabriel Santos Rosa Tiago Acosta de Oliveira Gessi Koakoski Darlan Gusso Murilo Sander de Abreu Ana Cristina Varrone Giacomini Heloísa Helena de Alcantara Barcellos Angelo L. Piato Leonardo José Gil Barcellos 《PloS one》2015,10(10)
The presence of drugs and their metabolites in surface waters and municipal effluents has been reported in several studies, but its impacts on aquatic organisms are not yet well understood. This study investigated the effects of acute exposure to the antipsychotic risperidone on the stress and behavioral responses in zebrafish. It became clear that intermediate concentration of risperidone inhibited the hypothalamic-pituitary-interrenal axis and displayed anxiolytic-like effects in zebrafish. The data presented here suggest that the presence of this antipsychotic in aquatic environments can alter neuroendocrine and behavior profiles in zebrafish. 相似文献
6.
Nag S Lehmann L Kettschau G Heinrich T Thiele A Varrone A Gulyas B Halldin C 《Bioorganic & medicinal chemistry》2012,20(9):3065-3071
The aim of this study was to synthesize and evaluate a novel fluorine-18 labeled analogue of rasagiline (6) as a PET radioligand for monoamine oxidase B (MAO-B). The corresponding non-radioactive fluorine-19 ligand, (1S,2S)-2-fluoro-N-(prop-2-yn-1-yl)indan-1-amine (4), was characterized in in vitro assays. The precursor compound (3aS,8aR)-3-(prop-2-yn-1-yl)-3,3a,8,8a-tetrahydroindeno[1,2-d][1,2,3]oxathiazole 2,2-dioxide (3) and reference standard 4 were synthesized in multi-step syntheses. Recombinant human MAO-B and MAO-A enzyme preparations were used in order to determine IC(50) values for compound 4 by use of an enzymatic assay employing kynuramine as substrate. Radiolabeling was accomplished by a two-step synthesis, compromising a nucleophilic substitution followed by hydrolysis of the sulphamidate group. Human whole hemisphere autoradiography (ARG) was performed with [(18)F]fluororasagiline. Blocking experiments with pirlindole (MAO-A), L-deprenyl and rasagiline (MAO-B) were conducted to demonstrate the specificity of the binding. A positron emission tomography (PET) study was carried out in a cynomolgus monkey where time activity curves for whole brain and regions with high and low MAO-B activity were recorded. Radiometabolites were measured in monkey plasma using gradient HPLC. Compound 4 inhibited MAO-B with an IC(50) of 27 nM and MAO-A with an IC(50) of 2.3 μM. Radiolabeling of precursor 3 and subsequent hydrolysis of the protecting group towards (1S,2S)-2-[(18)F]fluoro-N-(prop-2-yn-1-yl)indan-1-amine (6) was successfully accomplished with an radiochemical yield of 40-70%, a radiochemical purity higher than 99% and a specific radioactivity higher than 200GBq/μmol. ARG demonstrated selective binding for [(18)F]fluororasagiline (6) to MAO-B containing brain regions, for example, striatum. The initial uptake in the monkey brain was 250% SUV at 4 min post injection. The highest amounts of radioactivity were observed in the striatum and thalamus as expected whereas in the cortex and cerebellum lower levels were observed. Metabolite studies demonstrated 30% unchanged radioligand at 90 min post injection. Our investigations demonstrated that the new ligand [(18)F]fluororasagiline (6) binds specifically to MAO-B in vitro and has a MAO-B specific binding pattern in vivo. Thus, it could serve as a novel potential candidate for human PET studies. 相似文献
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Magnus Schou Carsten Steiger Andrea Varrone Denis Guilloteau Christer Halldin 《Bioorganic & medicinal chemistry letters》2009,19(16):4843-4845
A new dopamine transporter (DAT) ligand, (E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4′-methyl-phenyl) nortropane (FE-PE2I, 6), derived from PE2I (1), was prepared and found to be a potent inhibitor of rodent DAT in vitro. Compound 6 was radiolabelled with fluorine-18 (t1/2 = 109.8 min) for PET studies in monkeys. In vivo PET measurements showed a regional distribution in brain that corresponds to the known distribution of DAT. This binding was specific, reversible and the kinetics of [18F]6 binding in brain were faster than for its lead compound, [11C]1. The possible presence of a hydroxymethyl-radiometabolite formed by oxidation in the 3β-benzylic position of [18F]6 warrants further detailed evaluation of the metabolism of [18F]6. [18F]6 is a potential radioligand for imaging DATs in the human brain with PET. 相似文献
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Simon N. Haydar Chiara Ghiron Laura Bettinetti Hendrick Bothmann Thomas A. Comery John Dunlop Salvatore La Rosa Iolanda Micco Martina Pollastrini Joanna Quinn Renza Roncarati Carla Scali Michela Valacchi Maurizio Varrone Riccardo Zanaletti 《Bioorganic & medicinal chemistry》2009,17(14):5247-5258
Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment associated with a variety of disorders including Alzheimer’s disease and schizophrenia. Alpha 7 nAChRs are expressed in brain regions associated with cognitive function, regulate cholinergic neurotransmission and have been shown to be down regulated in both schizophrenia and Alzheimer’s disease. Herein we report a novel, potent small molecule agonist of the alpha 7 nAChR, SEN12333/WAY-317538. This compound is a selective agonist of the α7 nAChR with excellent in vitro and in vivo profiles, excellent brain penetration and oral bioavailability, and demonstrates in vivo efficacy in multiple behavioural cognition models. The SAR and biological evaluation of this series of compounds are discussed. 相似文献