Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Embryonic rat hippocampal neurons were cultured in a serum-free defined medium (MEM/N3) either directly on poly-D-lysine (PDL) or on a confluent monolayer of postnatal cortical astrocytes, C6 glioma cells, or Rat2 fibroblasts. Neurons on PDL were grown in MEM/N3 or in MEM/N3 conditioned for 24 h by astrocytes or C6 cells. Membrane capacitance (Cm) and gamma-aminobutyric acid (GABA)-, glycine-, kainate-, and N-methyl-D-aspartate (NMDA)-induced currents were quantified using whole-cell patch-clamp recordings. Cm as well as the amplitude and the density of these currents in neurons cultured on astrocytes were significantly greater than those in neurons grown on PDL after 24 and 48 h. C6 cells mimicked astrocytes in promoting Cm and GABA-, glycine-, and NMDA-evoked, but not kainate-evoked, currents. Cm and currents in neurons grown on Rat2 cells were comparable to those in neurons on PDL. Astrocytes maintained in culture for 3 months were noticeably less effective than freshly prepared ones just grown to confluence. Suppression of spontaneous cytoplasmic Ca2+ (Ca[c]2+) elevations in astrocytes by 1,2-bis(2-aminophenoxy) ehane-N, N, N, N-tetraacetic acid acetoxymethyl ester (BAPTA-AM) loaded intracellularly blocked the observed modulatory effects. Medium conditioned by either astrocytes or C6 cells mimicked the effects of direct coculture of neurons on these cells in promoting Cm and amino acid-evoked currents. Inclusion of antagonists at GABA and glutamate receptors in coculture experiments blocked the observed effects. Thus, diffusible substances synthesized and/ or secreted by astrocytes in a Ca(c)2+-dependent manner can regulate neuronal growth and aminoacid receptor function, and these effects may involve neuronal GABA and glutamate receptors.
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PMID:Astrocytes regulate amino acid receptor current densities in embryonic rat hippocampal neurons. 936 56

The therapeutic efficacy of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate), an isomer of the intracellular messenger IP3, was analyzed for cytotoxic swelling and damage of glial cells in vitro from lactacidosis or glutamate. Lactacidosis and the interstitial accumulation of glutamate are prominent sequelae in ischemic or traumatic brain tissue. C6 glioma cells harvested from culture and suspended in a physiological medium were either exposed to pH 5.0 by administration of lactic acid, or to 1 mM glutamate at normal pH. Cell swelling and viability were quantified by blood flow cytometry. Addition of alpha-trinositol (3 mM) under control conditions at pH 7.4 resulted in transient cell shrinking to 96.5 +/- 1.3% of control within 3 min (p < 0.05). Lactacidosis of pH 5.0 led to an increase in cell volume to 139.7 +/- 1.3% within 20 min, whereas alpha-trinositol reduced the swelling response by approximately 25% (p < 0.01). In addition, cell viability was severely affected at pH 5.0 amounting to only 53.8 +/- 3.1% after 60 min. alpha-Trinositol was found to markedly improve cell viability; at 60 min 70.2 +/- 1.6% of the cells were still viable (p < 0.01). Addition of glutamate (1 mM) led to a steady increase in cell size, reaching 110% of control after 120 min, irrespective of wether alpha-trinositol was present or not. The attenuation of cell swelling may be attributed to an interference with pH-regulatory mechanisms, such as the Na+/H(+)-antiporter, while protection of cell viability might be caused be effects of alpha-trinositol on Ca(2+)-overload. On the other hand, the increase in cell volume by glutamate associated with its intracellular uptake was not influenced by alpha-trinositol.
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PMID:Effect of alpha-trinositol on swelling and damage of glial cells by lactacidosis and glutamate. 941 15

C6 glioma cells treated with 10 mM glutamate reduced intracellular GSH to one-seventh of the initial level, and induced cytolysis accompanied by apoptosis. The treated cells produced extracellular H2O2. The cytolysis of the C6 cells induced by glutamate was prevented by antioxidants such as N-acetylcysteine (NAC), ascorbic acid (ASC), catalase, and NaN3, iron chelators such as deferoxamine and 1,10-phenanthroline, and oxygen radical scavengers such as 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) and alpha-phenyl-tert-butyl nitrone (PBN). The effect of these antioxidants, iron chelators, and oxygen radical scavengers on the cytolysis of C6 cells was dependent on the dose and the intracellular GSH level. Furthermore, 1-2 Mbp chromosomal DNA (giant DNA) fragments were observed during cytolysis. The giant DNA fragments were further cleaved into smaller DNA fragments of 200-800 kbp, and then to fragments of less than 300 kbp in size including chromosomal ladder DNA fragments. Such serial chromosomal DNA degradations induced by glutamate were also inhibited by addition of these antioxidants, iron chelators, and oxygen radical scavengers. These findings suggest that glutamate induces GSH depletion, and consequently, apoptosis through endogenously produced active oxygen species in C6 glioma cells and that the apoptosis is accompanied by 1-2 Mbp giant DNA fragmentation prior to the internucleosomal DNA fragmentation.
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PMID:Active oxygen-mediated chromosomal 1-2 Mbp giant DNA fragmentation into internucleosomal DNA fragmentation in apoptosis of glioma cells induced by glutamate. 943 54

Increased ammonia has been considered a key factor in the pathogenesis of hepatic encephalopathy. The high concentration of ammonia interferes with oxidative metabolism in the brain through an inhibitory effect on the tricarboxylic acid cycle (TCA). Inhibition of the TCA cycle may result in depletion of ATP. Due to the involvement of astrocytes in brain detoxification of ammonia, these cells are good candidates for studying ammonia's effect on energy stores in the brain. C6-glioma cells, which have altered glycolytic rates, may show greater sensitivity to the toxicity of ammonium chloride than astrocytes. To study the effect of ammonium chloride on energy storage of both astrocytes and C6-glioma, we observed the acute and chronic effects of NH4Cl (7.5 or 15 mM) on the metabolism of isolated astrocytes and C6-glioma cells. Primary astrocytes were isolated from the cerebral hemispheres of 1-2 day old Sprague-Dawley rats, and C6-glioma cells were purchased from the American Type Culture Collection (ATCC). Following treatment of the cells with ammonia, glucose, lactate, glutamate, ATP, and PCr were assayed. Our data showed that at 15 min following treatment with NH4Cl, there were no significant differences in the concentration of metabolites measured in astrocytes. However, following 15 min of treatment with NH4Cl, the concentration of some metabolites, for example, ATP and lactate, changed significantly in C6-glioma cells. We have shown that 24 h of treatment was sufficient time to see significant biochemical changes but not morphological changes in either cell type. Simultaneous biochemical and morphological changes were observed 48 h following treatment in C6-glioma cells and at 9-10 days following treatment in primary astrocytes. In primary astrocytes at 24 h following treatment, glucose utilization increased. This high utilization of glucose was in accordance with the increase in lactate and glutamate production and the decrease in ATP and PCr formation. In C6-glioma cells the utilization of glucose increased but this high utilization of glucose was consistent with a significant decrease in the concentration of lactate, glutamate and ATP.
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PMID:Effect of ammonium chloride on energy metabolism of astrocytes and C6-glioma cells in vitro. 947 2

Neuronal and glial sodium-dependent transporters are crucial for the control of extracellular glutamate levels in the CNS. The regulation of these transporters is relatively unexplored, but the activity of other transporters is regulated by protein kinase C (PKC)- and phosphatidylinositol 3-kinase (PI3K)-mediated trafficking to and from the cell surface. In the present study the C6 glioma cell line was used as a model system that endogenously expresses the excitatory amino acid carrier 1 (EAAC1) subtype of neuronal glutamate transporter. As previously observed, phorbol 12-myristate 13-acetate (PMA) caused an 80% increase in transporter activity within minutes that cannot be attributed to the synthesis of new transporters. This increase in activity correlated with an increase in cell surface expression of EAAC1 as measured by using a membrane-impermeant biotinylation reagent. Both effects of PMA were blocked by the PKC inhibitor bisindolylmaleimide II (Bis II). The putative PI3K inhibitor, wortmannin, decreased L-[3H]-glutamate uptake activity by >50% within minutes. Wortmannin decreased the Vmax of L-[3H]-glutamate and D-[3H]-aspartate transport, but it did not affect Na+-dependent [3H]-glycine transport. Wortmannin also decreased cell surface expression of EAAC1. Although wortmannin did not block the effects of PMA on activity, it prevented the PMA-induced increase in cell surface expression. This trafficking of EAAC1 also was examined with immunofluorescent confocal microscopy, which supported the biotinylation studies and also revealed a clustering of EAAC1 at cell surface after treatment with PMA. These studies suggest that the trafficking of the neuronal glutamate transporter EAAC1 is regulated by two independent signaling pathways and also may suggest a novel endogenous protective mechanism to limit glutamate-induced excitotoxicity.
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PMID:Multiple signaling pathways regulate cell surface expression and activity of the excitatory amino acid carrier 1 subtype of Glu transporter in C6 glioma. 950 8

Addition of 30mM glutamate to the culture medium decreased growth of rat glioma C6 cells accompanied by a decrease of DNA synthesis and an increase of lactate dehydrogenase (LDH) detected in the conditioned medium. The presence of 1 microM deprenyl attenuated the glutamate effect on cell growth only during the first 24-48 h incubation and had a minor influence on the glutamate-induced decrease of DNA synthesis. Clorgyline (1 microM) potentiated glutamate-induced DNA synthesis during the first 24 h incubation without significant influence on the cell growth. Deprenyl slightly attenuated the glutamate-induced LDH increase during 24 h incubation but potentiated the glutamate effect at 96 h. Clorgyline decreased the glutamate influence at 24 h and especially 96 h. All these effects were observed in the absence of exogenous monoamines in the culture medium. These results suggest that in transformed cells monoamine oxidase (MAO) inhibitors may influence processes of cell death via MAO-independent mechanisms.
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PMID:Modulation of glutamate neurotoxicity in the transformed cell culture by monoamine oxidase inhibitors, clorgyline and deprenyl. 956 11

Tumorous and contralateral rat brain was examined by in vivo single voxel proton NMR spectroscopy. Magnetization transfer (MT) experiments cause attenuation of various metabolite signals. Selective saturation of immobile metabolites was achieved by pulsed RF preirradiation. The method is compared with continuous wave MT generation. In contralateral tissue, MT attenuation is detected for both the CH3 and the CH2 protons of (phospho-)creatine (Cr + PCr) and for a signal at 3.44 ppm ascribed to taurine. Significant attenuation is also observed for a signal at 3.78 ppm that is commonly ascribed to the alphaCH proton of glutamate and glutamine (Glx); however, no effect is observed for the gammaCH2 protons of Glx. Within implanted F98 glioma tumors, only the CH3 signal of Cr + PCr shows significant MT attenuation. Although the MT effect detected for lactate in the tumors fails to reach significance, a significant effect is observed for the lactate signal acquired during 3 to 9 min postmortem.
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PMID:Magnetization transfer attenuates metabolite signals in tumorous and contralateral animal brain: in vivo observations by proton NMR spectroscopy. 958 5

The polyamines putrescine, spermidine and spermine are involved in the regulation of various metabolic processes. It is therefore desirable to detect and quantify the polyamines with NMR. We present the proton and carbon assignments for all polyamine signals obtained from PCA extracts of F98 glioma cells with high resolution using a semi-selective HSQC 2D-experiment. The biosynthesis of the polyamines in cell culture was examined using the labeled substrates [U-13C]glucose and [U-13C]glutamate. In such studies the high resolution of the semi-selective HSQC experiment at very high magnetic fields (14-19 T) allows the analysis of carbon-carbon couplings, and isotopomer patterns. The different effects of osmotic stress on the concentrations of polyamines and amino acids are also reported.
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PMID:A 1H/13C inverse 2D method for the analysis of the polyamines putrescine, spermidine and spermine in cell extracts and biofluids. 960 88

Exposure of rat C6 glioma cells to the beta-adrenergic receptor agonist isoproterenol potentiates basal and metabotropic glutamate receptor-stimulated phospholipase C activity in rat C6 glioma cells. After treatment of cells for 24 h with 10 microM isoproterenol, metabotropic glutamate receptors and phospholipase C activity were determined in C6 plasma membranes. Isoproterenol treatment caused an increase of 67% in the total number of binding sites (Bmax=12.1+/-1. 8 pmol/mg protein versus Bmax=20.27+/-0.88 pmol/mg protein) with Kd values of the same order (Kd=1250+/-101 nM versus Kd=1401+/-211 nM), using l-[3H]glutamate as radioligand. On the other hand, basal, guanylyl imidodiphosphate (Gpp[NH]p)- and trans-aminocyclopentane-1, 3-dicarboxylic acid (trans-ACPD)-stimulated phospholipase C activities were also significantly increased in membranes from isoproterenol-treated cells compared to control cells, by 337%, 33% and 40% respectively. Moreover, a significant increase of 94% in the steady-state level of phospholipase C beta1 in membranes from isoproterenol-treated cells compared to control was also detected by immunoblot. These results show that metabotropic glutamate receptors and its effector system, phospholipase C, are affected by isoproterenol treatment, showing the existence of cross-talk between these signal transduction pathways.
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PMID:Cross-talk between beta-adrenergic and metabotropic glutamate receptors in rat C6 glioma cells. 971

Cells from major types of gliomas, i.e. oligodendrogliomas and glioblastomas, are able to generate action potentials upon a current injection similar to neurons (Patt et al. (1996) Neuroscience, 71, 601-611; Labrakakis et al. (1997b) J. Neuropath. Exp. Neurol., 56, 243-254. Here, we report that activation of ionotropic glutamate receptors by the selective agonist, kainate, or by glutamate itself, depolarized the tumour cells in culture and living slices from tumour tissue, and can elicit volleys of action potentials, as recorded with the patch-clamp technique. Sixty-six percent of the glioblastoma cells, 44% of the astocytoma and 86% of the oligodendroglioma cells responded to glutamate and the specific agonist of AMPA/kainate receptors, kainate. The involvement of non-NMDA (N-methyl-D-aspartate) receptors is further supported by the observation that both kainate and glutamate currents were blocked by CNQX (6-cyano-7-nitroquinoxaline-2,3-dione). The receptor activation was accompanied by an increase in cytosolic Ca2+, as recorded with a fura-2 microfluorometric system. The Ca2+ elevation was mediated by the activation of Ca2+ channels due to membrane depolarization. The presence of voltage-gated Ca2+ channels was confirmed by patch-clamp experiments. Taken together, these findings imply that the electrophysiological properties of glioma cells are more reminiscent of those of neurons than of glial cells.
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PMID:Glutamate receptor activation can trigger electrical activity in human glioma cells. 975 1


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