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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate toxicity was studied in neuronal (SC9), glial (WC5), and neuroblastoma-glioma hybrid cell lines. In all three cell types, glutamate had a dual effect, depending on the concentration of glutamine in the culture medium. An expected dose-dependent cytotoxicity of the amino acid was observed when cells were cultured in medium containing the standard glutamine concentration (1-4 mM), but when the culture's glutamine content was decreased to 0.15-0.5 mM, glutamate had an apparent opposite, growth-promoting effect. The specificity of glutamate effect was indicated by the following: (a) it was stereospecific, with the L and not the D isomer being active; (b) monosodium aspartate was inactive in the presence of either high or low glutamine; and (c) monosodium glutamate and monopotassium glutamate had a similar dual effect. Furthermore, the glutamate receptor antagonist gamma-glutamylglycine blocked the amino acid cytotoxicity in a dose-dependent fashion. As glial cells are a major source of glutamine in the brain, neuronal-glial co-cultures were used to analyze the possible role of glial cells in glutamate neurotoxicity. It was found that SC9 cells were more sensitive to glutamate when co-cultured with WC5 cells. Continuous depolarization of the SC9 cells with KCl decreased cell number, but glutamate had no additive neurotoxic effect when added with KCl. We suggest that glutamine, glial cells, and neuronal activation play roles in modulating glutamate neurotoxicity, in developing as well as aged brains. It is tempting to speculate also that alterations in the glutamate/glutamine ratio under pathological conditions may take part in the etiology of some neurodegenerative diseases.
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PMID:Glutamate neurotoxicity in culture depends on the presence of glutamine: implications for the role of glial cells in normal and pathological brain development. 256 47

Glutamate binds to both excitatory neurotransmitter binding sites and a Cl(-)-dependent, quisqualate- and cystine-inhibited transport site on brain neurons. The neuroblastoma-primary retina hybrid cells (N18-RE-105) are susceptible to glutamate-induced cytotoxicity. The Cl(-)-dependent transport site to which glutamate and quisqualate (but not kainate or NMDA) bind has a higher affinity for cystine than for glutamate. Lowering cystine concentrations in the cell culture medium results in cytotoxicity similar to that induced by glutamate addition in its morphology, kinetics, and Ca2+ dependence. Glutamate-induced cytotoxicity is directly proportional to its ability to inhibit cystine uptake. Exposure to glutamate (or lowered cystine) causes a decrease in glutathione levels and an accumulation of intracellular peroxides. Like N18-RE-105 cells, primary rat hippocampal neurons (but not glia) in culture degenerate in medium with lowered cystine concentration. Thus, glutamate-induced cytotoxicity in N18-RE-105 cells is due to inhibition of cystine uptake, resulting in lowered glutathione levels leading to oxidative stress and cell death.
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PMID:Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. 257 75

Glutamate is thought to be a major excitatory neurotransmitter in the central nervous system. To study the glutamate receptor and its regulation under carefully controlled conditions, the specific binding of [3H]glutamate was characterized in washed membranes isolated from a neuroblastoma X retina hybrid cell line, N18-RE-105. [3H]Glutamate bound in a saturable and reversible fashion with an apparent dissociation constant, KD, of 650 nM and a maximum binding capacity, Bmax, of 16 pmol/mg of protein. Pharmacologic characterization of the site indicates that it closely resembles the Na+-independent binding site for glutamate found on brain membranes and thought to be an excitatory amino acid neurotransmitter receptor. Thus, while kainate, N-methyl-DL-aspartate, and nonamino acid ligands did not displace [3H]glutamate, quisqualate and ibotenate were potent inhibitors of specific binding. Furthermore, this binding site is regulated by ions in a manner which resembles that described in the hippocampus (Baudry, M., and Lynch, G. (1979) Nature (Lond.) 282, 748-750). Calcium (10 mM) increased the number of binding sites 2.6-fold with no change in receptor-ligand affinity. Lanthanum (1 mM) was the only other cation added which enhanced (3-fold) the binding of [3H]glutamate. Monovalent cations resulted in a decrease in the number of glutamate binding sites. Incubation of membranes in the presence of chloride ions caused a marked increased in [3H] glutamate binding, an effect which was synergistic with that of calcium incubation. Thus, N18-RE-105 cells possess a binding site for [3H]glutamate pharmacologically similar to an excitatory neurotransmitter binding site in brain and which exhibits regulatory properties resembling those previously described in hippocampal membranes, providing an excellent model for mechanistic studies.
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PMID:Characterization of a glutamic acid neurotransmitter binding site on neuroblastoma hybrid cells. 614 15

Glutamate is thought to be a major excitatory neurotransmitter in the vertebrate brain. In the preceding paper (Malouf, A. T., Schnaar, R. L., and Coyle, J. T. (1984) J. Biol. Chem. 259, 12756-12762), we demonstrated specific binding of [3H]glutamate to membranes from a neuroblastoma hybrid cell line, N18-RE-105. These sites are pharmacologically and kinetically similar to those seen on rat brain membranes and are regulated by ions added to the isolated membranes. In the current paper, we describe an additional level of regulation for the glutamate receptor in this cell line. Long-term incubation (72 h) of intact N18-RE-105 cells with glutamate (10 mM) results in a 2- to 3-fold increase in [3H]glutamate binding. Scatchard analysis reveals that the increase in binding is due to an increase in the number of glutamate receptors without significant change in their affinity. The ability of glutamate analogs to induce such up-regulation mirrors their ability to compete for [3H]glutamate binding to isolated membranes, suggesting that up-regulation is receptor-mediated. Binding of [3H]glutamate to membranes isolated from cells grown in the presence of glutamate can be further up-regulated by brief exposure (10 min) of the isolated membranes to calcium ions. This suggests that agonist-induced and calcium-induced up-regulation occur via independent mechanisms. The short-term ion-induced up-regulation and the long-term agonist-induced up-regulation described in this paper may model two levels of synaptic potentiation reported to occur in the vertebrate hippocampus. The N18-RE-105 cell line may offer a homogeneous cell type in which to study the molecular mechanisms underlying these phenomena.
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PMID:Agonists and cations regulate the glutamic acid receptors on intact neuroblastoma hybrid cells. 614 16

Culture of neuroblastoma cells in a medium of low-thiamine concentration (6 nM) and in the presence of the transport inhibitor amprolium leads to the appearance of overt signs of necrosis; i.e., the chromatin condenses in dark patches, the oxygen consumption decreases, mitochondria are uncoupled, and their cristae are disorganized. Glutamate formed from glutamine is no longer oxidized and accumulates, suggesting that the thiamine diphosphate-dependent alpha-ketoglutarate dehydrogenase activity is impaired. When thiamine (10 microM) is added to the cells, the O2 consumption increases, respiratory control is restored, and normal cell and mitochondrial morphology is recovered within 1 h. Succinate, which is oxidized via the thiamine diphosphate-independent succinate dehydrogenase, is also able to restore a normal O2 consumption (with respiratory control) in digitonin-permeabilized thiamine-deficient cells. Our results therefore suggest that the slowing of the citric acid cycle is the main cause of the biochemical lesion induced by thiamine deficiency as observed in Wernicke's encephalopathy.
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PMID:Thiamine deficiency--induced partial necrosis and mitochondrial uncoupling in neuroblastoma cells are rapidly reversed by addition of thiamine. 759 5

The 26-kDa protein encoded by the bcl-2 gene is a regulator of cell survival and blocks cell death induced by numerous stimuli. Amyloid beta protein (ABP) and glutamate are believed to play important roles in the neuronal cell death that occurs in Alzheimer's disease and stroke, respectively. Glutamate induces apoptosis in some neuronal cell systems, but it remains controversial whether ABP-mediated cell death occurs through apoptosis or necrosis. To further explore the pathways for cell death that are activated by these neurotoxins, we examined the effects of elevated levels of the p26-Bcl-2 protein on the susceptibility of neuronal cell lines to killing by glutamate and ABP. Gene transfer methods were used to elevate p26-Bcl-2 protein levels in the rat nerve lines PC-12 and B50 and the human neuroblastoma IMR-5. Bcl-2 protected all 3 cell lines from glutamate induced cell death but had no effect on killing mediated by ABP.
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PMID:BCL-2 prevents killing of neuronal cells by glutamate but not by amyloid beta protein. 790 32

In the present study, we have attempted to clarify whether neuroblastoma glioma hybrid NG 108-15 cells (NG cells) possess the NMDA receptor complex using [45Ca2+]influx and [3H]MK-801 binding as functional measures. Glutamate and NMDA dose-dependently increased [45Ca2+]influx and these increases were further enhanced by glycine. Scatchard analysis revealed the presence of a high-affinity binding site for [3H]MK-801 with a KD of 18.8 nM and a Bmax of 0.328 pmol/mg protein. This [3H]MK-801 binding was also increased by NMDA in a dose-dependent manner and this increase was further enhanced by glycine. Both ketamine and MK-801 inhibited glutamate- and NMDA-induced [45Ca2+]influx as well as the increase of [3H]MK-801 binding in a dose-dependent manner. Similarly, Mg2+ and Zn2+ dose-dependently reduced both glutamate-induced [45Ca2+]influx and [3H]MK-801 binding. Spermine, one of the polyamines, showed a biphasic stimulatory effects on glutamate-induced [45Ca2+]influx and [3H]MK-801 binding. These results indicate that NG cells possess a pharmacologically distinct NMDA receptor complex and suggest that these cells may be useful for the analyses on pharmacological and biochemical characteristics of the NMDA receptor complex.
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PMID:Presence of N-methyl-D-aspartate (NMDA) receptors in neuroblastoma x glioma hybrid NG108-15 cells-analysis using [45Ca2+]influx and [3H]MK-801 binding as functional measures. 791

1. The effects of hypoosmotic stress on cell volume and amino acid efflux were evaluated in the human neuroblastoma cell line CHP-100 with the Coulter Counter Multisizer and radiolabeled amino acid efflux, respectively. 2. CHP-100 cells swelled by approximately 35 +/- 5% (means +/- SE) when the osmolarity of the solution was decreased from 290 to 190 mOsm/kg H2O. The rapid swelling was followed by a biphasic regulatory volume decrease (RVD). 3. In cells loaded with 14C-taurine, hypoosmotic stress induced a 300 +/- 22% (n = 23, P < 0.05) increase in taurine efflux compared with controls. This efflux was inhibited by the chloride channel blockers 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), 4,4'-diisothio-cyanostilbene-2,2'-disulfonic acid (DIDS), niflumic acid and by the volume-activated anion channel blocker tamoxifen. In addition, the swelling-activated taurine efflux was dependent upon extracellular calcium. 4. Similarly, in cells loaded with 14C-glycine, hypoosmotic stress significantly increased glycine efflux, which was also sensitive to NPPB. In contrast, efflux of 3H-glutamate was not significantly altered after hypoosmotic stress. 5. With the use of patch clamp recording techniques, Cl- channels were activated in cell attached patches after exposure to hypoosmotic solutions. 6. In nystatin perforated patches, permeability of the hypoosmotically activated anion channel was observed to be SCN- > I- > Br- > Cl- >> Glutamate. 7. It is concluded that in CHP-100 cells, anion channels are activated during hypoosmotic stress and these channels represent a pathway for efflux of amino acids.
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PMID:Swelling-activated amino acid efflux in the human neuroblastoma cell line CHP-100. 887 Nov 97

Na+-K+-2Cl- cotransporters are important in renal salt reabsorption and in salt secretion by epithelia. They are also essential in maintenance and regulation of ion gradients and cell volume in both epithelial and nonepithelial cells. Expression of Na+-K+-2Cl- cotransporters in brain tissues is high; however, little is known about their function and regulation in neurons. In this study, we examined regulation of the Na+-K+-2Cl- cotransporter by the excitatory neurotransmitter glutamate. The cotransporter activity in human neuroblastoma SH-SY5Y cells was assessed by bumetanide-sensitive K+ influx, and protein expression was evaluated by Western blot analysis. Glutamate was found to induce a dose- and time-dependent stimulation of Na+-K+-2Cl- cotransporter activity in SH-SY5Y cells. Moreover, both the glutamate ionotropic receptor agonist N-methyl-D-aspartic acid (NMDA) and the metabotropic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) significantly stimulated the cotransport activity in these cells. NMDA-mediated stimulation of the Na+-K+-2Cl- cotransporter was abolished by the selective NMDA-receptor antagonist (+)-MK-801 hydrogen maleate. trans-ACPD-mediated effect on the cotransporter was blocked by the metabotropic receptor antagonist (+)-alpha-methyl-(4-carboxyphenyl)glycine. The results demonstrate that Na+-K+-2Cl- cotransporters in neurons are regulated by activation of both ionotropic and metabotropic glutamate receptors.
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PMID:Stimulation of Na+-K+-2Cl- cotransporter in neuronal cells by excitatory neurotransmitter glutamate. 973 Sep 61

Oxidative stress may be an important factor in several pathological brain conditions. A contributing factor in many such conditions is excessive glutamate release, and subsequent glutamatergic neuronal stimulation, that causes increased production of reactive oxygen species (ROS), oxidative stress, excitotoxicity and neuronal damage. Glutamate release is also associated with illnesses such as Alzheimer's disease, stroke, and brain injury. Glutamate may interact with an environmental toxin, lead, and this interaction may result in neuronal damage. Glutamate-induced ROS production is greatly amplified by lead in cultured neuronal cells. Alterations in protein kinase C (PKC) activity seem to be important both for glutamate-induced ROS production, and for the amplification of glutamate-induced ROS production by lead. It is possible that the neurotoxic effects of lead are amplified through glutamate-induced neuronal excitation. Cholinergic stimulation can also trigger ROS production in neuronal cells. PKC seems to play a key-role also in cholinergic-induced ROS production superoxide anion being the primary reactive oxygen species. There seems to be a close relationship between the responses of cholinergic muscarinic and glutamatergic receptors because glutamate receptor antagonists inhibit cholinergic-induced activation of human neuroblastoma cells. Glutamatergic neuronal stimulation may be a common final pathway in several brain conditions in which oxidative stress and ensuing excitotoxicity plays a role.
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PMID:Glutamate-stimulated ROS production in neuronal cultures: interactions with lead and the cholinergic system. 974 27


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