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

We used 31P-NMR spectroscopy to investigate the response of living C6 glioma cells to stimulation by a beta-adrenergic agonist, isoproterenol. In the presence of 3-isobutyl-1-methylxanthine, stimulation induced an accumulation of cAMP, making possible the NMR detection of the second messenger in living cells grown on microcarrier beads and perfused in the NMR tube. The cAMP signal rose to a maximum level within 20-25 min of stimulation; thereafter it decreased to the detection threshold within 60 min. At the same time, 40% increases of phosphomonoester and diphosphodiester signals were observed, whereas no significant change in phosphocreatine and nucleotide signals was detected. The kinetics of changes of the cellular content in phosphorylated metabolites were analyzed after recording 31P-NMR spectra of cell perchloric acid extracts as a function of time of stimulation. cAMP accumulation in stimulated cells was evidenced by a near linear increase of its NMR signal as a function of incubation time (from 0 to 60 min). Concomitantly with the production of cAMP, the data showed 30% decreases of phosphocreatine and ATP levels within 60 min of stimulation, and an unexpected redistribution of pyrimidine and purine nucleoside triphosphates. At the same time, levels of phosphomonoesters (phosphorylcholine and phosphorylethanolamine) and phosphodiesters (glycerophosphorylcholine and glycerophosphorylethanolamine) rose (50% increase). 13C-NMR spectra of cell perchloric acid extracts prepared after isoproterenol stimulation of cells incubated in the presence of [1-13C]glucose indicated a higher glucose content in stimulated cells, whereas the resonance of ribose C1 was diminished. Moreover, the resonances of C1 of ethanolamine and choline (and their derivatives) were increased in spectra of stimulated cells, whereas that of C3 of serine was decreased. In addition, the 13C-NMR data indicated that neither the pattern of glutamate carbon enrichment nor the glutamate/glutamine ratio was modified in stimulated cells. On the other hand, the heteronuclear coupling pattern of the lactate (methyl group) resonance in 1H-NMR spectra of cell incubation media indicated that no change occurred in the carbon flux through the pentose-phosphate shunt under stimulation. The results of this multinuclear NMR approach are discussed in terms of metabolic responses of C6 cells to beta-adrenergic stimulation and cAMP overproduction.
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PMID:Beta-adrenergic stimulation of C6 glioma cells: effects of cAMP overproduction on cellular metabolites. A multinuclear NMR study. 133 May 56

Experimental brain tumors produced in rats (n = 10) by stereotactic implantation of cells from the F98 anaplastic glioma clone into the right caudate nucleus were studied in vivo using localized proton NMR and in vitro using high-resolution proton NMR, bioluminescent imaging of lactate, ATP and glucose distributions, and fluorescent imaging of regional pH. In vivo spectra from normal brain contralateral to the tumor regions showed resonances assignable to N-acetyl aspartate (NAA), creatines, choline-containing compounds, myo-inositol, glutamate and glucose in a pattern similar to those obtained from normal anaesthetized rats. In vivo tumor spectra were characterized by the almost complete absence of NAA, a substantial reduction of total creatine and glucose, and an increase of cholines. Based on the in vitro spectra the increase of the myo-inositol signal observed in vivo was mainly attributed to glycine. Histological examination as well as bioluminescent and fluorescent imaging indicated two stages of tumor development, i.e., solid vital tumors and tumors with necrosis. However, there was no consistent relationship between proton NMR observations and tumor development.
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PMID:Localized proton NMR spectroscopy of experimental gliomas in rat brain in vivo. 133 73

Electrophysiological techniques and Xenopus oocytes were used to study the expression of neurotransmitter receptors encoded by mRNAs isolated from three human glioma cell lines. Oocytes injected with mRNAs from two glioblastoma cell lines did not show electrical responses to the various neurotransmitters tested. In contrast, oocytes injected with mRNA from an astrocytoma cell line (R-111) acquired acetylcholine and glutamate receptors as well as a small number of N-methyl-D-aspartate (NMDA) receptors. Acetylcholine elicited oscillatory Cl- currents that were abolished by muscarinic antagonists. The muscarinic receptors are coupled to the inositol phosphate-Ca2+ receptor-channel coupling system. Glutamate and its analogs kainate, quisqualate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid induced smooth currents. The non-NMDA responses were potently blocked by 6,7-dinitroquinoxaline-2,3 dione. Our results show that human astrocytoma cells contain mRNAs coding for functional acetylcholine and glutamate receptors that have properties similar to those of neurons. In contrast, human glioblastoma cells lacked those mRNAs. These differences might be useful for the development of new diagnostic and therapeutic procedures.
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PMID:mRNA coding for neurotransmitter receptors in a human astrocytoma. 134 61

We have demonstrated that addition of L-glutamate in millimolar amounts to a culture of C6 glioma cells induced cell death within 24 h. The glutamate-induced toxicity in the C6 glioma cells was completely suppressed by adding L-cystine (0.4-1.0 mM), while the C6 cells degenerated in L-cystine-deprived culture medium. Kinetic studies of [35S]cystine and [3H]glutamate uptake showed that cystine competitively inhibited glutamate uptake, and conversely glutamate inhibited cystine uptake competitively, suggesting that C6 cells have a cystine/glutamate antiporter (system CG or Xc) similar to that already described in the periphery. Exogenous cystine (1 mM) stimulated a release of endogenous glutamate from C6 cells in a Na(+)-independent Cl(-)-dependent fashion. Thus, the antiporter normally transports glutamate out of and cystine into the cells. With the glutamate analogues tested, there was a good correlation between cytotoxicity and inhibition of cystine uptake. The de novo synthesis of glutathione was largely dependent upon the uptake of extracellular cystine. Intracellular levels of glutathione were dramatically decreased within 8-10 h by culture in glutamate-added or cystine-free medium. Vitamin E (100 microM), an antioxidant, rescued the death of C6 cells induced by glutamate exposure or by culture in cystine-deprived medium, but did not restore the apparent decrease of intracellular glutathione. Taken together, the present data strongly indicate that glutamate-induced cell death is initially due to inhibition of cystine uptake through the antiporter Xc system; such inhibition leads to glutathione depletion exposing the cells to oxidative stress. Excess of extracellular glutamate introduced from endogenous or exogenous roots might disorder this mechanism, resulting in cell death.
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PMID:A mechanism for glutamate toxicity in the C6 glioma cells involving inhibition of cystine uptake leading to glutathione depletion. 135 66

The synthesis of nerve growth factor (NGF) and nerve growth factor receptor (NGFR) were studied in a C6 glioma cell line by Northern blot hybridization. In response to a glutamate agonist N-methyl-D-aspartic acid (NMDA), NGF mRNA increased by up to 2-fold after 4-12 h of culture. The non-NMDA receptor agonists, quisqualate and kainate, did not induce any increase of NGF mRNA, and kainate actually produced a decrease. The increase in NGF mRNA in response to NMDA was dose-dependent at 1, 5 and 10 microM. NGF receptor (NGFR) mRNA showed changes in expression which were similar to those for NGF mRNA, but were less marked. The specific glutamate antagonist 2-aminophosphonovaleric acid (APV) blocked the increase of NGF mRNA produced by NMDA. In the absence of Ca2+, an increase of NGF mRNA was still observed but in the presence of 1 mM ethylglycol-bis-(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA), NGF mRNA production abolished. The mechanism producing an increase in NGF mRNA by NMDA may be mediated by cyclic AMP since intracellular cyclic AMP and NGF mRNA levels both increased following treatment with NMDA or dibutyryl cyclic AMP.
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PMID:Regulation of nerve growth factor and nerve growth factor receptor production by NMDA in C6 glioma cells. 135 54

Phosphatidylserine synthesis was studied in glioma C6 cells with [14C]serine and in the presence or absence of agents which increase the level of [Ca2+]i. It was found that glutamate and acetylcholine inhibited this synthesis by up to 40%, whereas thapsigargin and the ionophore A23187 inhibited by up to 70%. The inhibitory effect of thapsigargin and the A23187 was observed in Ca(2+)-free medium. The data show that the inhibition of this synthesis is caused by the Ca(2+)-depletion from endoplasmic reticulum, suggesting that the synthesis of phosphatidylserine occurs on the luminal side of these structures and can be regulated by transmembrane signaling systems.
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PMID:Inhibition of phosphatidylserine synthesis by glutamate, acetylcholine, thapsigargin and ionophore A23187 in glioma C6 cells. 135 59

The mechanisms of glutamate-induced glial swelling have been studied using an in vitro model that permits detection of cell volume changes with high accuracy. The model allows for a close control of the extracellular environment to study in isolation the effect of defined extracellular alterations occurring in brain under pathophysiologic conditions. Glutamate was applied in concentrations between 50 microM and 10 mM to either C6 glioma cells or astrocytes from primary culture. Glutamate uptake was assessed by HPLC measurements of amino acids in the extracellular medium. Glutamate at all concentrations tested caused glial swelling, which, however, was moderate, with maximal average volume increases between 5.0 +/- 1.92 and 18.38 +/- 1.6% of control at 50 microM and 5 mM glutamate, respectively. Swelling was concentration dependent and correlated with glutamate uptake. After removal of all extracellular glutamate by glial uptake, cell volume spontaneously normalized. Pretreatment of the cells for 90 min with ouabain (1 mM) to abolish the extracellular/intracellular Na+ gradient, prevented glutamate-induced swelling. It is concluded that while glial cells readily accumulate glutamate from the extracellular environment to protect neurons from excitotoxic effects, swelling results from the increase of intracellular osmotic activity due to the uptake of Na+ and glutamate.
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PMID:Mechanisms of glial swelling induced by glutamate. 136 32

In order to establish new interferon therapy against malignant glioma by selective transfection of its gene, we developed a novel transfection system using liposomes bearing positive charges on their surface and entrapping plasmids containing the HuIFN- beta gene (pSV2IFN-beta). The liposomes were composed of N-(alpha -trimethylammonioacetyl) -didodecyl-D-glutamate chloride (TMAG), dilauroylphosphatidylcholine (DLPC), and dioleoylphosphatidylethanolamine (DOPE) as a molar ratio of 1:2:3. The liposomes were not observed to have cytotoxicity for human glioma cells, when applied at a rate less than 15nmol/ml. This liposome-mediated transfection of the gene into the cultured glioma cells (U-251-MG) resulted in the secretion of HuIFN- beta into the medium. The HuIFN- beta level in the culture media of glioma cells reached 23 IU/ml after 96h of incubation. When the pSV2IFN-beta containing liposomes were coupled with a monoclonal antibody (G-22 MCA) against glioma-associated antigen (G-22), the level of HuIFN-beta in the medium was 181 IU/ml, resulting in a 7-fold increase. It was indicated that this transfection system was a safe and selective method in the case of TMAG/DLPC/DOPE liposomes.
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PMID:[Basic research for interferon gene therapy against malignant glioma]. 159 30

Nuclear magnetic resonance (NMR) spectroscopy was used to study the metabolism of cells from the central nervous system both in vitro on perchloric acid extracts obtained either from cultured tumoral cells (C6 rat glioma) or rat astrocytes in primary culture, and in vivo within the human brain. Analysis of carbon 13 NMR spectra of perchloric acid extracts prepared from cultured cells in the presence of NMR [1-13C] glucose as substrate allowed determination of the glutamate and glutamine enrichments in both normal and tumoral cells. Preliminary results indicated large changes in the metabolism of these amino acids (and also of aspartate and alanine) in the C6 cell as compared to its normal counterpart. Localized proton NMR spectra of the human brain in vivo were obtained at 1.5 T, in order to evaluate the content of various metabolites, including glutamate, in peritumoral edema from a selected volume of 2 x 2 x 2 cm3. N-acetyl aspartate, glutamate, phosphocreatine, creatine, choline and inositol derivative resonances were observed in 15 min spectra. N-acetyl-aspartate was found to be at a lower level in contrast to glutamate which was detected at a higher level in the injured area as compared to the contralateral unaffected side.
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PMID:Magnetic resonance spectroscopy and metabolism. Applications of proton and 13C NMR to the study of glutamate metabolism in cultured glial cells and human brain in vivo. 167 32

Clonal lines of murine neuroblastoma (NBP2) and rat glioma (C6) were used to investigate the effects of methylmercuric chloride (CH3HgCl). Glioma cells were more sensitive to CH3HgCl than NB cells on the criterion of growth inhibition, but these cells were equally sensitive to inorganic mercury (HgCl1), Tri-n-butyl lead acetate and acrylamide on the same criterion. Alpha-tocopherol, alpha-tocopheryl++ succinate and inhibitors of cAMP phosphodiesterase protected glioma cells against the growth-inhibitory effect of CH3HgCl, but they failed to protect NB cells in culture. Glioma factors, sodium ascorbate, non-inhibitory concentrations of prostaglandins E1 (PGE1), and glutamate enhanced the growth-inhibitory effect of CH3HgCl on both NB and glioma cells in culture. The levels of certain specific cAMP-dependent and -independent protein phosphorylations appear to be very sensitive to CH3HgCl, and can be altered in both cell types by concentrations of CH3HgCl which do not affect growth or morphology of these cells.
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PMID:New opportunities with neuronal cultures to study the mechanisms of neurotoxic injuries. 174 37


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