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1.
Carlos Hermenegildo Goizane Marcaida Carmina Montoliu Santiago Grisolía María-Dolores Miñana Vicente Felipo 《Neurochemical research》1996,21(10):1237-1244
We proposed that acute ammonia toxicity is mediated by activation of NMDA receptors. To confirm this hypothesis we have tested
whether different NMDA receptor antagonists, acting on different sites of NMDA receptors, prevent death of mice induced by
injection of 14 mmol/Kg of ammonium acetate, a dose that induces death of 95% of mice. MK-801, phencyclidine and ketamine,
which block the ion channel of NMDA receptors, prevent death of at least 75% of mice. CPP, AP-5, CGS 19755, and CGP 40116,
competitive antagonists acting on the binding site for NMDA, also prevent death of at least 75% of mice. Butanol, ethanol
and methanol which block NMDA receptors, also prevent death of mice. There is an excellent correlation between the EC50 for preventing ammonia-induced death and the IC50 for inhibiting NMDA-induced currents. Acute ammonia toxicity is not prevented by antagonists of kainate/AMPA receptors, of
muscarinic or nicotinic acetylcholine receptors or of GABA receptors. Inhibitors of nitric oxide synthase afford partial protection
against ammonia toxicity while inhibitors of calcineurin, of glutamine synthetase or antioxidants did not prevent ammonia-induced
death of mice. These results strongly support the idea that acute ammonia toxicity is mediated by activation of NMDA receptors. 相似文献
2.
Elena Kosenko Yuri Kaminsky Eugenio Grau María-Dolores Miñana Goizane Marcaida Santiago Grisolía Vicente Felipo 《Journal of neurochemistry》1994,63(6):2172-2178
Abstract: Injection of large doses of ammonia into rats leads to depletion of brain ATP. However, the molecular mechanism leading to ATP depletion is not clear. The aim of the present work was to assess whether ammonium-induced depletion of ATP is mediated by activation of the NMDA receptor. It is shown that injection of MK-801, an antagonist of the NMDA receptor, prevented ammonia-induced ATP depletion but did not prevent changes in glutamine, glutamate, glycogen, glucose, and ketone bodies. Ammonia injection increased Na+ ,K+ -ATPase activity by 76%. This increase was also prevented by previous injection of MK-801. The molecular mechanism leading to activation of the ATPase was further studied. Na+ ,K+ -ATPase activity in samples from ammonia-injected rats was normalized by "in vitro" incubation with phorbol 12-myristate 13-acetate, an activator of protein kinase C. The results obtained suggest that ammonia-induced ATP depletion is mediated by activation of the NMDA receptor, which results in decreased protein kinase C-mediated phosphorylation of Na+ ,K+ -ATPase and, therefore, increased activity of the ATPase and increased consumption of ATP. 相似文献
3.
Ricardo Sánchez David Pantoja-Uceda Jesús Prieto Tammo Diercks María J. Marcaida Guillermo Montoya Ramón Campos-Olivas Francisco J. Blanco 《The Journal of biological chemistry》2010,285(29):22196-22201
Gadd45α is a nuclear protein encoded by a DNA damage-inducible gene. Through its interactions with other proteins, Gadd45α participates in the regulation of DNA repair, cell cycle, cell proliferation, and apoptosis. The NMR structure of human Gadd45α has been determined and shows an α/β fold with two long disordered and flexible regions at the N terminus and one of the loops. Human Gadd45α is predominantly monomeric in solution but exists in equilibrium with dimers and other oligomers whose population increases with protein concentration. NMR analysis shows that Aurora A interacts through its N-terminal domain with a region of human Gadd45α encompassing the site of dimerization, suggesting that the oligomerization of Gadd45α could be a regulatory mechanism to modulate its interactions with Aurora A, and possibly with other proteins too. However, Gadd45α appears to interact only weakly with PCNA through its flexible loop, in contrast with previous and contradictory reports. 相似文献
4.
Goizane Marcaida Elena Kosenko María-Dolores Miñana Santiago Grisolía Vicente Felipo 《Journal of neurochemistry》1996,66(1):99-104
Abstract: In primary cultures of cerebellar neurons glutamate neurotoxicity is mainly mediated by activation of the NMDA receptor, which allows the entry of Ca2+ and Na+ into the neuron. To maintain Na+ homeostasis, the excess Na+ entering through the ion channel should be removed by Na+ ,K+ -ATPase. It is shown that incubation of primary cultured cerebellar neurons with glutamate resulted in activation of the Na+ ,K+ -ATPase. The effect was rapid, peaking between 5 and 15 min (85% activation), and was maintained for at least 2 h. Glutamate-induced activation of Na+ ,K+ -ATPase was dose dependent: It was appreciable (37%) at 0.1 µ M and peaked (85%) at 100 µ M . The increase in Na+ ,K+ -ATPase activity by glutamate was prevented by MK-801, indicating that it is mediated by activation of the NMDA receptor. Activation of the ATPase was reversed by phorbol 12-myristate 13-acetate, an activator of protein kinase C, indicating that activation of Na+ ,K+ -ATPase is due to decreased phosphorylation by protein kinase C. W-7 or cyclosporin, both inhibitors of calcineurin, prevented the activation of Na+ ,K+ -ATPase by glutamate. These results suggest that activation of NMDA receptors leads to activation of calcineurin, which dephosphorylates an amino acid residue of the Na+ ,K+ -ATPase that was previously phosphorylated by protein kinase C. This dephosphorylation leads to activation of Na+ ,K+ -ATPase. 相似文献
5.
Marcaida MJ Schlarb-Ridley BG Worrall JA Wastl J Evans TJ Bendall DS Luisi BF Howe CJ 《Journal of molecular biology》2006,360(5):968-977
Cytochrome c6A is a unique dithio-cytochrome present in land plants and some green algae. Its sequence and occurrence in the thylakoid lumen suggest that it is derived from cytochrome c6, which functions in photosynthetic electron transfer between the cytochrome b6f complex and photosystem I. Its known properties, however, and a strong indication that the disulfide group is not purely structural, indicate that it has a different, unidentified function. To help in the elucidation of this function the crystal structure of cytochrome c6A from Arabidopsis thaliana has been determined in the two redox states of the heme group, at resolutions of 1.2 A (ferric) and 1.4 A (ferrous). These two structures were virtually identical, leading to the functionally important conclusion that the heme and disulfide groups do not communicate by conformational change. They also show, however, that electron transfer between the reduced disulfide and the heme is feasible. We therefore suggest that the role of cytochrome c6A is to use its disulfide group to oxidize dithiol/disulfide groups of other proteins of the thylakoid lumen, followed by internal electron transfer from the dithiol to the heme, and re-oxidation of the heme by another thylakoid oxidant. Consistent with this model, we found a rapid electron transfer between ferro-cytochrome c6A and plastocyanin, with a second-order rate constant, k2=1.2 x 10(7) M(-1) s(-1). 相似文献
6.
Molecular basis of histone H3K4me3 recognition by ING4 总被引:1,自引:0,他引:1
Palacios A Muñoz IG Pantoja-Uceda D Marcaida MJ Torres D Martín-García JM Luque I Montoya G Blanco FJ 《The Journal of biological chemistry》2008,283(23):15956-15964
7.
Grossmann JG Callaghan AJ Marcaida MJ Luisi BF Alcock FH Tokatlidis K Moulin M Haertlein M Timmins P 《European biophysics journal : EBJ》2008,37(5):719-611
Many macromolecules in the cell function by forming multi-component assemblies. We have applied the technique of small angle neutron scattering to study a nucleic acid-protein complex and a multi-protein complex. The results illustrate the versatility and applicability of the method to study macromolecular assemblies. The neutron scattering experiments, complementing X-ray solution scattering data, reveal that the conserved catalytic domain of RNase E, an essential ribonuclease in Escherichia coli (E. coli), undergoes a marked conformational change upon binding a 5'monophosphate-RNA substrate analogue. This provides the first evidence in support of an allosteric mechanism that brings about RNA substrate cleavage. Neutron contrast variation of the multi-protein TIM10 complex, a mitochondrial chaperone assembly comprising the subunits Tim9 and Tim10, has been used to determine a low-resolution shape reconstruction of the complex, highlighting the integral subunit organization. It shows characteristic features involving protrusions that could be assigned to the six subunits forming the complex. 相似文献
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9.
María-Dolores Miñana Elena Kosenko Goizane Marcaida Carlos Hermenegildo Carmina Montoliu Santiago Grisolía Vicente Felipo 《Cellular and molecular neurobiology》1997,17(4):433-445
1. Previous results suggest that glutamine synthesis in brain could be modulated by nitrix oxide. The aim of this work was to assess this possibility.2. As glutamine synthetase in brain is located mainly in astrocytes, we used primary cultures of astrocytes to assess the effects of increasing or decreasing nitrix oxide levels on glutamine synthesis in intact astrocytes.3. Nitric oxide levels were decreased by adding nitroarginine, an inhibitor of nitric oxide synthase. To increase nitric oxide we used S-nitroso-N-acetylpenicillamine, a nitric oxide generating agent.4. It is shown that S-nitroso-N-acetylpenicillamine decreases glutamine synthesis in intact astrocytes by 40–50%. Nitroarginine increases glutamine synthesis slightly in intact astrocytes.5. These results indicate that brain glutamine synthesis may be modulated in vivo by nitric oxide. 相似文献
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