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

Both glial and neuronal cells maintained in primary culture were found to accumulate [3H]GABA by an efficient "high-affinity" uptake system (apparent Km = 9 muM, Vmax = 0.018 and 0.584 nmol/mg/min, respectively) which required sodium ions and was inhibited by 1 mM ouabain. Strychnine and parachloromercuriphenylsulfonate (pCS) (both at 1mM) also strongly inhibited uptake of [3H]GABA, but metabolic inhibitors (2,4-dinitrophenol, potassium cyanide, and malonate) were without effect. Only three structural analogs of GABA (nipecotate, beta-alanine, and 2,4-diaminobutyrate) inhibited uptake of [3H]GABA, while several other compounds with structural similarities to GABA (e.g. glycine, L-proline, and taurine) did not interact with the system. The kinetic studies indicated presence of a second uptake (Km = 92 muM, Vmax = 0.124 nmol/mg/min) in the primary cultures containing predominantly glioblasts. On the other hand, only one of the neuronal cell lines transformed by simian virus SV40 appeared to accumulate [3H]GABA against a concentration gradient. Apparent Km of this uptake was relatively high (819 muM), and it was only weakly inhibited by 1 mM ouabain and 1 mM pCS. The structural specificity also differed from that of the uptake observed in the primary cultures. Significantly, non of the nontransformed continuous cell lines of either tumoral (glioma, C6; neuroblastoma, M1; M1NN) or normal (NN;I6) origin actively accumulated [3H]GABA. It is suggested that for the neurochemical studies related to GABA and requiring homogeneous cell populations, the primary cultures offer a better experimental model than the continuous cell lines.
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PMID:High-affinity uptake of gamma-aminobutyric acid in cultured glial and neuronal cells. 22 77

The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG):cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06-0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.
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PMID:Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line. 179 58

Guanylate cyclase was activated 3- to 10-fold by hemin in a dose-dependent manner in membranes prepared from homogenates of rat lung, C6 rat glioma cells, or B103 rat neuroblastoma cells. Maximum activation was observed with 50 to 100 microM hemin with higher concentrations being inhibitory. Activation was observed when Mg2+-GTP but not when Mn2+-GTP was used as the substrate. Increased enzyme activity reflected selective activation of the particulate form of guanylate cyclase; hemin inhibited the soluble form of guanylate cyclase 70 to 90% over a wide range of concentrations. Activation was not secondary to proteolysis since a variety of protease inhibitors failed to alter stimulation by hemin. Protophorphyrin IX had little effect on particulate guanylate cyclase activity and sodium borohydride almost completely abolished hemin-dependent activation. These data suggest a requirement for the ferric form of the porphyrin-metal chelate for activation. However, agents which interact with the iron nucleus of porphyrins, such as cyanide, had little effect on the ability of hemin to activate guanylate cyclase. The stimulatory effects of hemin were observed in the presence of detergents such as Lubrol-PX, and highly purified particulate enzyme could be activated to the same extent as enzyme in native membranes. These data suggest that the interaction of porphyrins with particulate guanylate cyclase is complex in nature and different from that with the soluble enzyme.
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PMID:Selective activation of particulate guanylate cyclase by a specific class of porphyrins. 614 94

The neuroblastoma x glioma hybrid clone NG108-15 is able to release acetylcholine upon depolarization and form cholinergic neuromuscular synapses in culture. Normal functioning of cholinergic synapses is thought to be dependent on the ability of a neuron to take up extracellular choline, since neurons are unable to synthesize choline de novo. For these two reasons it became important to characterize the choline uptake system of NG108-15 cells. The uptake system appears to bear little if any resemblance to the Na+-dependent high-affinity choline uptake system normally associated with cholinergic neurons. Although the cells appear to possess both high- and low-affinity choline uptake systems, neither system is dependent on Na+ and uptake actually is increased about 60% by the substitution of sucrose for NaCl. Acetylcholine synthesis also is not dependent on Na+, since sucrose, substituted for NaCl, also stimulates acetylcholine synthesis. Changes in the concentrations of the other ions in the uptake medium have little effect on uptake, with the exception that elevated Ca2+ or Mg2+ reverses the stimulation of choline uptake produced by substitution of sucrose for NaCl. Choline uptake is inhibited by hemicholinium-3, but only at high concentrations of the drug (IC50 = 30-80 microM). The metabolic poisons cyanide and iodoacetate inhibit uptake by only 30-40%. Growth of the cells in N6,O2' dibutyryladenosine-3',5'-cyclic monophosphate, which promotes functional and morphological differentiation of the cells, decreased slightly the total amount of choline taken up but had no additional effect on the uptake system. Thus, it appears that NG108-15 cells are capable of forming functional cholinergic synapses with muscle cells even though the neuroblastoma does not possess the high-affinity choline uptake system normally associated with cholinergic neurons.
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PMID:Choline uptake by the neuroblastoma x glioma hybrid, NG108-15. 625 99

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

1. The effect on membrane potential (Em) of low external [K+]o, [Na+]o and [Ca2+]o and of metabolic inhibitors was studied in cultured human glial cells (U-787CG) and human glioma cells (Tp-483MG and U-251MG). Whole cells were voltage or current clamped with the tight-seal recording technique. 2. Em was -76 and -80 mV in glial and glioma cells (mean values in U-787CG and U-251MG, respectively) in a reference external solution with 3.0 mM K+. K(+)-free external solution caused a rapid and reversible depolarization of these cells by about 26 and 42 mV (respectively). 3. Block of K+ channels with 1 mM Ba2+ in external solution rapidly depolarized the cells (U-251MG) by about 35 mV. 4. Na(+)-free solutions caused a delayed depolarization by 40-50 mV, which was slowly reversible (in 2 min). 5. Ouabain (1 mM) depolarized the cells by about 4 mV. It did not prevent the effect of K(+)-free solution. 6. Ca(2+)-free external solution rapidly depolarized the cells to Em about -17 mV. The combination of either Na(+)-K(+)-free or Na(+)-Ca(2+)-free solution transiently repolarized the cell, which indicated that the K+ selectivity of the membrane was decreased in both K(+)- and Ca(2+)-free solutions. 7. Metabolic inhibitors (carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP) and 2,4-dinitrophenol (DNP)) rapidly and reversibly depolarized the cells. This effect was not prevented by intracellular perfusion of a strong Ca(2+)-buffering solution. 8. Voltage clamp revealed only minor changes (< 20%) in the leak conductance (g) of cells that were depolarized by the above-mentioned solutions. 9. Positive polarizing current elicited (in some cells) a regenerative depolarization. The threshold for depolarization was less in low external [K+]o. 10. It is concluded (a) that the resting potential of these glial cells depends on ion channels that are K+ selective only in the presence of external Ca2+ and K+ and (b) that this K+ selectivity may require that Em is near the reversal potential for potassium (EK), and (c) that the action of metabolic inhibitors (DNP and FCCP) is different from that in neurones.
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PMID:Effect of external cation concentration and metabolic inhibitors on membrane potential of human glial cells. 848

We report that 2,3-naphthalenedicarboxaldehyde reacts rapidly with glutathione and its precursor, gamma-glutamylcysteine, to form highly fluorescent derivatives under physiological conditions. In contrast to previous accounts of 2,3-naphthalenedicarboxaldehyde labeling of primary amines, no additional CN- ion or any other additional nucleophile is required. The fluorescence spectral properties of the chromophores (lambda exc max = 472 nm, lambda em max = 528 nm) make these derivatives amenable to excitation and detection by optical instrumentation that is optimized for fluorescein wavelengths. This selective labeling chemistry enabled quantitative determination and histochemical localization of glutathione in neurobiological samples. Intracellular glutathione was labeled by incubating cultured cells or cell suspensions in a 2,3-naphthalenedicarboxaldehyde-supplemented, DMSO-containing physiological buffer (pH = 7.4) for 2-10 min. Applications include imaging of cultured NG 108-15 cells (mouse neuroblastoma x rat glioma) and primary glial and neuronal cell cocultures (rat hippocampus) using epiluminescent and confocal fluorescence microscopy. Quantitative determination of glutathione in single NG 108-15 cells was accomplished using laser-induced fluorescence detection and capillary electrophoresis.
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PMID:Use of 2,3-naphthalenedicarboxaldehyde derivatization for single-cell analysis of glutathione by capillary electrophoresis and histochemical localization by fluorescence microscopy. 863 71

Studies were conducted to determine the effects of bath application of the protonophores carbonyl cyanide m-chlorophenylhydrazone (CCCP) and carbonyl cyanide p-(trifluoromethoxy)-phenylhydrazone (FCCP) on membrane electrical characteristics of differentiated NG108-15 (neuroblastoma X glioma hybrid) cells. Membrane resting potential (Vm), input resistance (R(in)) and electrically induced action potential generation were measured using intracellular micro-electrode techniques. Both compounds produced concentration-dependent depolarization rather than the hyperpolarization commonly found with other central mammalian neurons. CCCP and FCCP also reduced R(in) and disrupted the generation of action potentials in a concentration-dependent manner. The contribution of the observed alterations to the in vivo toxicity of these compounds remains to be established.
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PMID:Effects of protonophores on membrane electrical characteristics in NG108-15 cells. 1078 11

The store-operated calcium influx into electrically non-excitable cells is greatly modified under the condition of deenergized mitochondria in situ. The rate of calcium influx into cells with empty intracellular calcium stores is greatly diminished when cells were pretreated with 2 microM carbonyl cyanide m-chlorophenylhydrazone (a mitochondrial uncoupler) or with 4 microM myxothiazol (an inhibitor of the respiratory chain). We demonstrate that this general phenomenon takes place in the case of transformed (glioma C6 and Ehrlich ascites tumor cells) as well as non-transformed (human fibroblasts) cells. We also demonstrate that the deenergization of mitochondria affects the cellular calcium influx rate and not the calcium pump on the plasma membrane.
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PMID:The role of mitochondrial dysfunction in regulation of store-operated calcium channels in glioma C6 and human fibroblast cells. 1093 May 75

The effects of different calcium-mobilizing agents on cell death were characterized in NG108-15 neuroblastoma x glioma hybrid cells. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) increased the cytosolic Ca(2+) concentration ([Ca(2+)](i)) and caused cell death. Thapsigargin (TG) not only increased the [Ca(2+)](i) and caused cell death but also induced neurite outgrowth via activation of phospholipase A(2) and cytochrome P450 epoxygenase. In contrast, bradykinin increased the [Ca(2+)](i), but had no effect on cell morphology or cell death. Cell death occurred by two different mechanisms, one of which was caspase-3-dependent and the other caspase-3-independent. Caspase-3 activation was Ca(2+)-dependent, whereas neurite outgrowth was Ca(2+)-independent. TG- or FCCP-induced caspase-3 activation occurred at the same time, but the cell death induced by TG was delayed. TG treatment did not enhance the generation of nitric oxide or cAMP or secretion of glial-derived neurotrophic factor or neurotrophin-3, but activated sphingosine kinase. Furthermore, inhibition of sphingosine kinase accelerated TG-induced cell death, and exogenous sphingosine 1-phosphate (S1P) protected cells from FCCP-induced cell death by about 60%. These results indicate that, in these cells, depletion of intracellular nonmitochondrial or mitochondrial Ca(2+) stores causes cell death, that TG activates phospholipase A(2) and sphingosine kinase, and that arachidonic acid induces neurite outgrowth, whereas S1P delays cell death.
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PMID:Distinct effects of different calcium-mobilizing agents on cell death in NG108-15 neuroblastoma X glioma cells. 1185 28


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