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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytotoxic effects of L-glutamate and related compounds were investigated on rat glioma C6 cells in vitro. Within 12-24 h, addition of glutamate to the culture medium, resulted in degeneration of the C6 cells. The ED50 for glutamate-induced damage was about 4 mM. Seventeen structural analogues of glutamate, including agonists and antagonists for glutamate receptors as well as glutamate-uptake inhibitor, were examined concerning their toxicity on C6 cells. Among them, L-aminoadipic acid, DL-aminopimelic acid, DL-homocysteic acid, L-cysteic acid, quisqualic acid, L-glutamic acid diethyl ester and 2-amino-4-phosphonobutyric acid elicited similar degeneration at comparable concentrations. The D-isomer of glutamate was not cytotoxic. Following differentiation of C6 cells with 1 mM dibutyryl cyclic AMP or 3 mM sodium butyrate, they were no longer susceptible to L-glutamate and L-aminoadipate. C6 cells treated with 10 microM hydrocortisone, which is known to induce glutamine synthetase activity, were also resistant to L-glutamate, but not to L-aminoadipate. The decomposition of cellular DNA in glutamate-treated cultures was confirmed by flow cytometer analysis. The results demonstrate that the sensitivity of C6 cells to glutamate-induced cytotoxicity was modified by cellular metabolic conditions. This indicates that cultured glioma C6 cells are a useful model system to investigate the molecular mechanism of glutamate gliotoxicity in vitro.
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PMID:Sensitive and insensitive states of cultured glioma cells to glutamate damage. 614 80

The phenotypic expression of cells derived from human anaplastic astrocytomas, rat glioma, normal human adult and foetal brain tissue have been examined for differentiated and malignancy-associated properties. Glial fibrillary acidic protein (GFAP), high affinity glutamate and gamma-amino butyric acid (GABA) uptake and glutamine synthetase were used as indicators of astroglial differentiation. Plasminogen activator and tumour angiogenesis factor were the malignancy-associated markers. The normal adult brain-derived lines showed some differentiated astroglial features and expressed low levels of the malignancy-associated properties. The foetal cultures contained highly differentiated astroglia while the glioma lines showed considerable phenotypic heterogeneity from highly differentiated to undifferentiated. The least differentiated glioma cells exhibited the highest plasminogen activator activities. The density-dependent control of phenotypic expression was also investigated. High affinity GABA uptake, and GFAP in rat C6 glioma cultures, increased with increasing monolayer cell density, events probably mediated by an increase in the formation of cell-cell contacts at confluence. Plasminogen activator activity decreased with increasing cell density.
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PMID:Interrelationship between differentiation and malignancy-associated properties in glioma. 620 Jan 30

The transport of radiolabeled L-glutamic acid by LRM55 glioma cells in culture was examined. Time course studies indicated that L-[3H]glutamic acid is rapidly accumulated, and then 3H is lost from the cell, presumably in the form of glutamate metabolites. Kinetic analysis of L-glutamate uptake provided evidence for two components of transport. A low affinity component was found to persist at 0 to 4 degrees C and was not saturable, influx being proportional to the substrate concentration. A high affinity component, resolved by subtraction of the influx at 0 to 4 degrees C, followed Michaelis-Menten kinetics having a Km of 123 microM and a Vmax of 2.99 nmol/min/mg of protein. The transport system was highly substrate-specific: At least 27-fold larger concentrations of the most potent analogues--cysteic acid, cysteine sulfinic acid, and L-aspartic acid--were required to compete effectively with glutamate. Second, the system was not severely affected by exposure to inhibitors of oxidative phosphorylation or gamma-glutamyltranspeptidase. Third, only 65% of the high affinity uptake was dependent upon the presence of sodium, the other 35% being dependent upon chloride. These observations were supported by the findings that uptake was only partially inhibited by ouabain and quite effectively reduced by several inhibitors of chloride transport. The results of this study provide information on the properties of low affinity glutamate transport, as well as the first description of sodium-independent, chloride-dependent high affinity glial transport. The high affinity component of influx is stimulated by elevated potassium and inhibited by several pharmacological agents. The sodium independence of a significant proportion of high affinity glutamate transport suggests that glutamate binding studies done in sodium-free medium with intact cells may be confounded by a considerable amount of intracellular uptake.
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PMID:Characterization of L-glutamic acid transport by glioma cells in culture: evidence for sodium-independent, chloride-dependent high affinity influx. 620 76

The effects of triethyltin (TET) on the transport of taurine, glutamate, lysine, Na+, K+ (using 86Rb+ as tracer), and Cl- by LRM55 glioma cells were examined. Taurine transport was inhibited by TET at much lower concentrations (IC50 = 2.5 microM) than either glutamate or lysine transport (135 and 110 microM, respectively). TET had no significant effect on Na+, Cl-, or 86Rb+ influx at the low concentrations greater than 100 microM. The failure of low concentrations (less than or equal to 10 microM) of TET to affect ion transport indicated that inhibition of taurine transport was not secondary to effects of TET on ion movements or gradients. This conclusion was supported by the observation that neither ouabain nor furosemide, which do affect ion movement and gradients, strongly inhibited taurine transport. Uncouplers and inhibitors of oxidative phosphorylation (cyanide, 2,4-dinitrophenol, and carbonyl cyanide-m-chlorophenyl hydrazone) also had only small effects on taurine transport, suggesting that inhibition by TET was not secondary to possible effects on oxidative phosphorylation. TET had no effect on the efflux of taurine from LRM55 cells at the low concentrations that inhibit uptake, but it induced a nonspecific increase in membrane permeability at much higher concentrations (greater than 100 microM). Tri-n-propyltin and tri-n-butyltin were also potent inhibitors of taurine transport (IC50 = 2.3 and 11 microM, respectively), but trimethyltin was much less potent (144 microM).
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PMID:Inhibitory effect of triethyltin on taurine transport by glioma cells. 663 82

SITS, an inhibitor of anion exchange, was found to be a potent and selective inhibitor of L-glutamic acid uptake by cultured LRM55 glioma cells and rat brain astrocytes. Synaptosomal uptake of glutamate was relatively insensitive to inhibition by SITS. This differential effect indicates that the glutamate transport system in glia differs from that in neurons and that SITS may provide a tool for investigating the exclusive neuronal transport and metabolism of L-glutamic acid.
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PMID:Selective inhibition of glial versus neuronal uptake of L-glutamic acid by SITS. 687 92

Diffusion-weighted in vivo 1H-NMR spectroscopy of F98 glioma cells embedded in basement membrane gel threads showed that the initial cell swelling to about 180% of the original volume induced under hypotonic stress was followed by a regulatory volume decrease to nearly 100% of the control volume in Dulbecco's modified Eagle's medium (DMEM) but only to 130% in Krebs-Henseleit buffer (KHB, containing only glucose as a substrate) after 7 h. The initial cell shrinkage to approx. 70% induced by the hypertonic stress was compensated by a regulatory volume increase which after 7 h reached almost 100% of the control value in KHB and 75% in DMEM. 1H-, 13C- and 31P-NMR spectroscopy of perchloric acid extracts showed that these volume regulatory processes were accompanied by pronounced changes in the content of organic osmolytes. Adaptation of intra- to extracellular osmolarity was preferentially mediated by a decrease in the cytosolic taurine level under hypotonic stress and by an intracellular accumulation of amino acids under hypertonic stress. If these solutes were not available in sufficient quantities (as in KHB), the osmolarity of the cytosol was increasingly modified by biosynthesis of products and intermediates of essential metabolic pathways, such as alanine, glutamate and glycerophosphocholine in addition to ethanolamine. The cellular nucleoside triphosphate level measured by in vivo 31P-NMR spectroscopy indicated that the energy state of the cells was more easily sustained under hypotonic than hypertonic conditions.
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PMID:Changes in organic solutes, volume, energy state, and metabolism associated with osmotic stress in a glial cell line: a multinuclear NMR study. 747 72

In the present study the effect of cocaine on thymidine, uridine and leucine incorporation was assessed in primary cortical glial and C6 glioma cells. Cocaine exposure for 24 h inhibited thymidine and uridine incorporation in cortical glial and C6 glioma cells. However, the effect of cocaine on uridine incorporation was less prominent compared to thymidine incorporation. High concentrations of cocaine inhibited leucine incorporation in C6 glioma cells but not in cortical glia. Cocaine exposure for four days decreased cell proliferation of cortical glial and C6 glioma cells. Cocaine-induced attenuation of macromolecular syntheses was not due to cell death since cocaine-treated cells were not stained with Trypan Blue and did not release lactate dehydrogenase into culture supernatants. Furthermore, cocaine had no effect on glutamate uptake either in cortical glia or in C6 glioma cells. These results indicate that cocaine inhibits macromolecular syntheses in glial cells. The inhibition of macromolecular syntheses in glial cells may be the mechanism involved in cocaine-induced fetal brain growth retardation.
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PMID:Effect of cocaine on macromolecular syntheses and cell proliferation in cultured glial cells. 750 70

The changes in ionic permeability induced by the application of alpha-latrotoxin to NG108-15 neuroblastoma x glioma cells were examined using the nystatin perforated-patch technique for whole-cell recording. Complex single channel activity appeared in the plasmalemmas after delays that ranged from 1-20 min in Krebs' solution. The conductance of a channel fluctuated among at least three broad, approximately equispaced bands, the maximum conductance being about 300 pS, and the reversal potential approximately 0 mV. The channels were permeable to Na+, K+, Ca2+ and Mg2+, poorly permeable to glucosamineH+ and Cl-, and were blocked by La3+. The channels stayed fully open in Ca(2+)-free solutions with 4 mM Mg2+, in solutions with no divalent cations and in solutions with 2 mM Ca2+ and 96 mM Mg2+. They opened infrequently if both internal and external Cl- were replaced by glutamate-. If alpha-latrotoxin opened similar channels in nerve terminals, the flux of ions through them could account for the massive release of neurotransmitter induced by the toxin.
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PMID:Alpha-latrotoxin channels in neuroblastoma cells. 751 70

It was recently shown that addition of L-glutamate in millimolar amounts to a culture of C6 glioma cells induced cell death within 24 h. The mechanism for glutamate toxicity in the C6 glioma cells is linked to the inhibition of cystine uptake, leading to glutathione depletion through the cystine/glutamate antiporter (Xc) system. In the present study, neurotransmitters, whose receptors were localized on the glioma (glial) cells, were evaluated for their ability to protect C6 cells from glutamate toxicity through this amino acid antiporter. Among them, only 100 microM serotonin suppressed cell death by glutamate in a constant co-existence culture. The suppressive dose of serotonin was relatively low and the half-effective dose was about 35 microM. 8-Hydroxy-2-(DL-n-propylamino)tetralin, a specific serotonin1A agonist, showed a comparable suppression to glutamate damage, while 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, a specific serotonin2 agonist, and quipazine, a non-selective serotonin1B agonist, did not suppress it. Furthermore, propranolol and pindolol significantly blocked the serotonin effect, but spiperone, mianserin and ketanserin did not block it. These results strongly indicate that this protective action of serotonin to glutamate toxicity was receptor (serotonin1A) mediated. Serotonin did not protect the C6 cells from glutathione depletion by glutamate. The cellular level of glutathione was depleted even under the co-existence of serotonin and glutamate. Serotonin induced a significant inhibition of lipid peroxide accumulation in the C6 glioma cells to glutamate exposure and the low rate of lipid peroxide accumulation was controlled.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin protects C6 glioma cells from glutamate toxicity. 752 Jan 31

We found in cultured glioma (C6BU-1) cells that excitatory amino acids (EAAs) such as glutamate, N-methyl-D-aspartate (NMDA), aspartate, and metabotropic glutamate receptor agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylate caused an increase in the inositol 1,4,5-trisphosphate formation and the intracellular Ca2+ concentration ([Ca2+]i) in the absence of extracellular Mg2+ and Ca2+. Pertussis toxin treatment abolished this glutamate-induced [Ca2+]i increase. Various antagonists against NMDA receptor-ion channel complex, such as Mg2+, D-2-amino-5-phosphonovalerate (D-APV), HA-966, and MK-801, also inhibited the increase in [Ca2+]i induced by glutamate. These results indicate that these metabotropic EAA receptors coupled to pertussis toxin-susceptible GTP-binding protein and phospholipase C system in C6BU-1 glioma cells have the pharmacological properties of NMDA receptor-ion channel complexes. We also found that in the presence of Mg2+ these metabotropic receptors resemble the NMDA receptor-ion channel complex interacted with 5-hydroxytryptamine2 (5-HT2) receptor signaling. EAAs inhibited 5-HT2 receptor-mediated intracellular Ca2+ mobilization and inositol 1,4,5-trisphosphate formation in a concentration-dependent manner. The inhibitory effect of glutamate was reversed by various NMDA receptor antagonists (D-APV, MK-801, phencyclidine, and HA-966), but L-APV failed to block the inhibitory effect of glutamate. The same result was observed in the absence of extracellular Ca2+. In addition, this inhibitory effect on 5-HT2 receptor-mediated signal transduction was abolished by treatment of C6BU-1 cells with pertussis toxin, whereas 5-HT2 receptor-mediated [Ca2+]i increase was not abolished by pertussis toxin treatment. We can, therefore, conclude that the inhibitory effect of glutamate is not a result of the influx of Ca2+ through the ion channel and that it operates via metabotropic glutamate receptors, having NMDA receptor-ion channel complex-like properties and being coupled with pertussis toxin-sensitive GTP-binding protein and phospholipase C.
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PMID:Metabotropic glutamate receptor in C6BU-1 glioma cell has NMDA receptor-ion channel complex-like properties and interacts with serotonin2 receptor-stimulated signal transduction. 752 90


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