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Mg2+ Concentration (mg2+ + concentration)
Selected AbstractsThe NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidenceINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue S1 2003Wojciech Danysz Abstract There is increasing evidence for the involvement of glutamate-mediated neurotoxicity in the pathogenesis of Alzheimer's disease (AD). We suggest that glutamate receptors of the N-methyl-D-aspartate (NMDA) type are overactivated in a tonic rather than a phasic manner in this disorder. This continuous mild activation may lead to neuronal damage and impairment of synaptic plasticity (learning). It is likely that under such conditions Mg2+ ions, which block NMDA receptors under normal resting conditions, can no longer do so. We found that overactivation of NMDA receptors using a direct agonist or a decrease in Mg2+ concentration produced deficits in synaptic plasticity (in vivo: passive avoidance test and/or in vitro: LTP in the CA1 region). In both cases, memantine,an uncompetitive NMDA receptor antagonists with features of an ,improved' Mg2+ (voltage-dependency, kinetics, affinity),attenuated this deficit. Synaptic plasticity was restored by therapeutically-relevant concentrations of memantine (1,,M). Moreover, doses leading to similar brain/serum levels provided neuroprotection in animal models relevant for neurodegeneration in AD such as neurotoxicity produced by inflammation in the NBM or ,-amyloid injection to the hippocampus. As such, if overactivation of NMDA receptors is present in AD, memantine would be expected to improve both symptoms (cognition) and to slow down disease progression because it takes over the physiological function of magnesium. Copyright © 2003 John Wiley & Sons, Ltd. [source] Evidence for two conductive pathways in P2X7 receptor: differences in modulation and selectivityJOURNAL OF NEUROCHEMISTRY, Issue 3 2010Susanna Alloisio J. Neurochem. (2010) 113, 796,806. Abstract The P2X7 receptor (P2X7R) is an ATP-gated cation channel whose biophysical properties remain to be unravelled unequivocally. Its activity is modulated by divalent cations and organic messengers such as arachidonic acid (AA). In this study, we analysed the differential modulation of magnesium (Mg2+) and AA on P2X7R by measuring whole-cell currents and intracellular Ca2+ ([Ca2+]i) and Na+ ([Na+]i) dynamics in HEK293 cells stably expressing full-length P2X7R and in cells endowed with the P2X7R variant lacking the entire C-terminus tail (trP2X7R), which is thought to control the pore activation. AA induced a robust potentiation of the P2X7R- and trP2X7R-mediated [Ca2+]i rise but did not affect the ionic currents in both conditions. Extracellular Mg2+ reduced the P2X7R- and trP2X7R-mediated [Ca2+]i rise in a dose-dependent manner through a competitive mechanism. The modulation of the magnitude of the P2X7R-mediated ionic current and [Na+]i rise were strongly dependent on Mg2+ concentration but occurred in a non-competitive manner. In contrast, in cells expressing the trP2X7R, the small ionic currents and [Na+]i signals were totally insensitive to Mg2+. Collectively, these results support the tenet of a functional structure of P2X7R possessing at least two distinct conductive pathways one for Ca2+ and another for monovalent ions, with the latter which depends on the presence of the receptor C-terminus. [source] Glutamate-induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neuronsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2010Yutaka Shindo Abstract Excess administration of glutamate is known to induce Ca2+ overload in neurons, which is the first step in excitotoxicity. Although some reports have suggested a role for Mg2+ in the excitotoxicity, little is known about its actual contribution. To investigate the role of Mg2+ in the excitotoxicity, we simultaneously measured intracellular Ca2+ and Mg2+, using fluorescent dyes, Fura red, a fluorescent Ca2+ probe, and KMG-104, a highly selective fluorescent Mg2+ probe developed by our group, respectively. Administration of 100 ,M glutamate supplemented with 10 ,M glycine to rat hippocampal neurons induced an increase in intracellular Mg2+ concentration ([Mg2+]i). Extracellular Mg2+ was not required for this glutamate-induced increase in [Mg2+]i, and no increase in intracellular Ca2+ concentration ([Ca2+]i) or [Mg2+]i was observed in neurons in nominally Ca2+ -free medium. Application of 5 ,M carbonyl cyanide p -(trifluoromethoxy) phenylhydrazone (FCCP), an uncoupler of mitochondrial inner membrane potential, also elicited increases in [Ca2+]i and [Mg2+]i. Subsequent administration of glutamate and glycine following FCCP treatment did not induce a further increase in [Mg2+]i but did induce an additive increase in [Ca2+]i. Moreover, the glutamate-induced increase in [Mg2+]i was observed only in mitochondria localized areas. These results support the idea that glutamate is able to induced Mg2+ efflux from mitochondria to the cytosol. Furthermore, pretreatment with Ru360, an inhibitor of the mitochondrial Ca2+ uniporter, prevented this [Mg2+]i increase. These results indicate that glutamate-induced increases in [Mg2+]i result from the Mg2+ release from mitochondria and that Ca2+ accumulation in the mitochondria is required for this Mg2+ release. © 2010 Wiley-Liss, Inc. [source] Structure of d(GCGAAAGC) (hexagonal form): a base-intercalated duplex as a stable structureACTA CRYSTALLOGRAPHICA SECTION D, Issue 1 2004d(GCGAAAGC) A DNA fragment d(GCGAAAGC), postulated to adopt a stable mini-hairpin structure on the basis of its extraordinary properties, has been X-ray analyzed. Two octamers related by a crystallographic twofold symmetry are aligned in an antiparallel fashion and associate to form a duplex, which is maintained by two Watson,Crick G·C base pairs and a subsequent sheared G·A pair at both ends. The central two A residues are free from base-pair formation. The corresponding base moieties of the two strands are intercalated and stacked on each other, forming a long column of G1 -C2 -G3 -A4 -A -A5 -A -G -C -G (asterisks indicate the counter-strand). The Watson,Crick and major-groove sites of the four stacked adenine bases are exposed to the solvent region, suggesting a functional role. Since this structural motif is similar to those found in the nonamers d(GBrCGAAAGCT) and d(GICGAAAGCT), the base-intercalated duplex may be a stable form of the specific sequence. Electrophoresis results suggest that the octamer has two states, monomeric and dimeric, in solution depending on the Mg2+ concentration. The present duplex is preferred under the crystallization conditions, which correspond to physiologically allowed conditions. [source] Biosynthesis reaction mechanism and kinetics of deoxynucleoside triphosphates, dATP and dGTPBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2005Jie Bao Abstract The enzyme reaction mechanism and kinetics for biosyntheses of deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP) from the corresponding deoxyadenosine diphosphate (dADP) and deoxyguanosine diphosphate (dGDP) catalyzed by pyruvate kinase were studied. A kinetic model for this synthetic reaction was developed based on a Bi-Bi random rapid equilibrium mechanism. Kinetic constants involved in this pyruvate kinase catalyzed phosphorylation reactions of deoxynucleoside diphosphates including the maximum reaction velocity, Michaelis-Menten constants, and inhibition constants for dATP and dGTP biosyntheses were experimentally determined. These kinetic constants for dATP and dGTP biosyntheses are of the same order of magnitude but significantly different between the two reactions. Kinetic constants involved in ATP and GTP biosyntheses as reported in literature are about one order of magnitude different from those involved in dATP and dGTP biosyntheses. This enzyme reaction requires Mg2+ ion and the optimal Mg2+ concentration was also determined. The experimental results showed a very good agreement with the simulation results obtained from the kinetic model developed. This kinetic model can be applied to the practical application of a pyruvate kinase reaction system for production of dATP and dGTP. There is a significant advantage of using enzymatic biosyntheses of dATP and dGTP as compared to the chemical method that has been in commercial use. © 2005 Wiley Periodicals, Inc. [source] Comparison of Intrinsic Optical Signals Associated with Low Mg2+, and 4-Aminopyridine,Induced Seizure-Like Events Reveals Characteristic Features in Adult Rat Limbic SystemEPILEPSIA, Issue 6 2000Katharina Buchheim Summary: Purpose: To analyze the intrinsic optical signal change associated with seizure-like events in two frequently used in vitro models,the low-Mg2+ and the 4-aminopyridine (4-AP) models,and to monitor regions of onset and spread patterns of these discharges by using imaging of intrinsic optical signals (IOS). Methods: Combined hippocampal,entorhinal,cortex slices of adult rats were exposed to two different treatments: lowering extracellular Mg2+ concentrations or application of 100 ,M 4-AP. The electrographic features of the discharges were monitored using extracellular microelectrodes. Optical imaging was achieved by infrared transillumination of the slice and analysis of changes in light transmission using a subtraction approach. The electrographic features were compared with the optical changes. Regions of onset and spread patterns were analyzed in relevant anatomic regions of the slice. Results: Both lowering extracellular Mg2+ concentrations and application of 4-AP induced seizure-like events. The relative duration of the intrinsic optical signal change associated with seizure-like events in the low-Mg2+ model was significantly longer compared with that seen with those occurring in the 4-AP model, although duration of field potentials did not differ significantly in the two models. Seizure-like events of the low-Mg2+ model originated predominantly in the entorhinal cortex, with subsequent propagation toward the subiculum and neocortical structures. In contrast, no consistent region of onset or spread patterns were seen in the 4-AP model, indicating that the seizure initiation is not confined to a particular region in this model. Conclusions: We conclude that different forms of spontaneous epileptiform activity are associated with characteristic optical signal changes and that optical imaging represents an excellent method to assess regions of seizure onset and spread patterns. [source] High extracellular [Mg2+]-induced increase in intracellular [Mg2+] and decrease in intracellular [Na+] are associated with activation of p38 MAP kinase and ERK2 in guinea-pig heartEXPERIMENTAL PHYSIOLOGY, Issue 12 2008Shang-Jin Kim High extracellular Mg2+ concentrations ([Mg2+]o) caused a remarkable concentration-dependent and reversible increase in intracellular Mg2+ concentrations ([Mg2+]i) in beating and quiescent guinea-pig papillary muscles, accompanied by a definite decrease in intracellular Na+ concentrations ([Na+]i). A change in 1 mm[Mg2+]o evoked a direct change in 0.0161 mm[Mg2+]i and an inverse change in 0.0263 mm[Na+]i. Imipramine completely abolished the high [Mg2+]o -induced decrease in [Na+]i and remarkably diminished the high [Mg2+]o -induced increase in [Mg2+]i in papillary muscles. High [Mg2+]o also produced a significant activation of p38 mitogen-activated protein (MAP) kinase and extracellular signal-related kinase 2 (ERK2) that was inhibited by pretreatment with imipramine. These results suggest that the high [Mg2+]o -induced increase in [Mg2+]i could be coupled with the decrease in [Na+]i, which might involve activation of the reverse mode of Na+,Mg2+ exchange, accompanied by activation of p38 MAP kinase and ERK2 in the guinea-pig heart. [source] Role of Mg2+ and pH in the modification of Salmonella lipid A after endocytosis by macrophage tumour cellsMOLECULAR MICROBIOLOGY, Issue 2 2005Henry S. Gibbons Summary Lipid A of Salmonella typhimurium is covalently modified with additional acyl and/or polar substituents in response to activation of the PhoP/PhoQ and/or PmrA/PmrB signalling systems, which are induced by growth at low Mg2+ concentrations and mild acid pH respectively. Although these conditions are thought to exist within macrophage phagolysosomes, no direct evidence for lipid A modification after endocytosis has been presented. To address this issue, we grew S. typhimurium inside RAW264.7 cells in the presence of 32Pi, and then isolated the labelled lipid A fraction, which was found to be extensively derivatized ,with phosphoethanolamine, aminoarabinose, 2-hydroxymyristate and/or palmitate moieties. S. typhimurium grown in tissue culture medium synthesized lipid A molecules lacking all these substituents with the exception of the 2-hydroxymyristate chain, which was still present. Using defined minimal media to simulate the intracellular pH and Mg2+ concentrations of endosomes, we found that lipid A of S. typhimurium grown in an acidic, low-Mg2+ medium closely resembled lipid A isolated from bacteria internalized by RAW264.7 cells. A subset of S. typhimurium lipid A modifications were induced by low Mg2+ alone. Escherichia coli K-12 W3110 modified its lipid A molecules in response to growth under acidic but not low-Mg2+ conditions. Growth in a high-Mg2+, mildly alkaline medium resulted in suppression of most lipid A modifications with the exception of the 2-hydroxymyristate in S. typhimurium. Although lpxO transcription was stimulated by growth on low Mg2+, the biosynthesis of lipid A species containing 2-hydroxymyristate was independent of PhoP/PhoQ and PmrA/PmrB in S. typhimurium. Our labelling methods should be applicable to studies of lipid A modifications induced by endocytosis of diverse bacteria. [source] Sperm quality of Brazilian flounder Paralichthys orbignyanus throughout the reproductive seasonAQUACULTURE RESEARCH, Issue 9 2010Carlos Frederico Ceccon Lanes Abstract The aim of this study was to evaluate the sperm quality of Brazilian flounder Paralichthys orbignyanus throughout its reproductive season. Sperm was collected at the beginning, middle and end of the breeding period. Spermatozoa density was maximum at the beginning (12.7 ± 0.92 × 109 cells mL,1) and at the end (11.8 ± 0.39 × 109 cells mL,1) of the breeding season (P<0.05). Sperm production and the percentage of spermatozoa moving fast forward increased significantly towards the end of the breeding season (P<0.05). The mean duration of progressive motility of spermatozoa was around 10 min. No difference was observed during the reproductive season in the percentage of motile cells, pH, osmolality and K+, Cl, and Mg2+ concentrations in seminal plasma. The concentration of Na+ increased throughout the breeding season, reaching 174.62 ± 12.68 mmol L,1 at the end (P<0.05). There was a decline in the concentration of Ca2+ (12.31 ± 3.08 mmol L,1) in the middle of the breeding season, which coincided with the shortest motility duration of spermatozoa. The information reported in this study should help to improve management and optimize the development of protocols for short-term storage and cryopreservation of Brazilian flounder semen. [source] | |||||||||||||