Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the cellular mechanisms that lead to the generation of synaptic plasticity of neuronal cells, it is important to understand the intracellular responses of neuronal cells stimulated via synaptic transmission. The stimulation of mouse cerebellar granule cells via NMDA (N-methyl-D-aspartate) receptors caused an increase in deoxyribonucleic acid (DNA)-binding activities to TRE (12-O-tetradecanoylphorbol-13-acetate-responsive element) and CRE (adenosine 3',5'-cyclic monophosphate-responsive element) motifs, depending upon the presence of extracellular Ca2+. The increases in TRE- and CRE-binding activities were also detected with the stimulation of non-NMDA receptors by kainate. The increases in TRE- and CRE-binding activities were both mediated by the same DNA-binding complexes whose binding affinity to CRE was about three-fold higher than that to TRE. On the other hand, the stimulation of neuroblastoma x glioma hybrid NG108-15 via muscarinic acetylcholine receptors, alpha 2-adrenergic receptors and bradykinin receptors caused a rapid induction of zif/268. An additive effect on the induction of zif/268 was observed when the different stimuli were simultaneously added. Thus, it is extremely likely that signals transduced via synaptic transmission are transferred to the level of gene expression and evoke some events which might contribute to the generation of synaptic plasticity in neuronal cells. In addition, we have found that the direct injection of plasmid DNAs into mouse skeletal muscle with fructose, glucose or NaCl solution led to a long-term expression of the introduced gene in muscle cells.
 ...
PMID:[Genetical responses of neuronal cells to synaptic transmission]. 132 98

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.
 ...
PMID:Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. 257 75

The anti-hypertensive drug ifenprodil is known to interact potently with the alpha 1-adrenergic receptor as well as a number of other second messenger-linked receptors. In addition to these properties, ifenprodil has been shown to prevent glutamate-mediated excitotoxicity via non-competitive antagonism of NMDA receptors [Legendre and Westbrook (1991) Molec. Pharmac. 40: 289-298; Shalaby et al. (1992) J. Pharmac. Exp. Ther. 260: 925-932]. With these things in mind, we have begun to examine the specificity of ifenprodil for various ligand-gated ion channels using electrophysiological methods. While ifenprodil effectively inhibits NMDA-mediated currents in cortical neurons in culture, it does not interact with either kainate or GABA receptors. Surprisingly, ifenprodil also acts as a relatively potent antagonist of the 5-hydroxytryptamine3 (5-HT3) receptor in the NG108-15 neuroblastoma x glioma cell line. Furthermore, several aspects of ifenprodil action on the 5-HT3 receptor resemble its interaction with the NMDA receptor. Namely, inhibition of 5-HT3-mediated cation currents is readily reversible, has relatively slow onset, is non-competitive, and is not voltage dependent. Since most of the known 5-HT3 antagonists are competitive, it is possible that ifenprodil may define a unique modulatory site(s) on this neurotransmitter receptor.
 ...
PMID:Ifenprodil inhibition of the 5-hydroxytryptamine3 receptor. 756 98

The metabolism of L-tryptophan to the neuroactive kynurenine pathway metabolites, L-kynurenine, kynurenate and quinolinate, and the effects of two inhibitors of quinolinate synthesis (6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate) were investigated by mass spectrometric assays in cultured cells and in vivo. Cell lines obtained from astrocytoma, neuroblastoma, macrophage/monocytes, lung, and liver metabolized L-[13C6]-tryptophan to L-[13C6]kynurenine and [13C6]kynurenate, particularly after indoleamine-2,3-dioxygenase induction by interferon-gamma. Kynurenine aminotransferase activity was measurable in all cell types examined but was unaffected by interferon-gamma. These results suggest that many cell types can be sources of kynurenate following immune activation. In vivo synthesis of L-[13C6]kynurenine and [13C6]kynurenate from L-[13C6]tryptophan was studied in the CSF of macaques infected with poliovirus, as a model of inflammatory neurologic disease. The effects of 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate on the synthesis of kynurenate were different. 6-Chlorotryptophan attenuated formation of L-[13C6]kynurenine and [13C6]kynurenate and was converted to 4-chlorokynurenine and 7-chlorokynurenate. It may be an effective prodrug for the delivery of 7-chlorokynurenate, which is a potent antagonist of NMDA receptors. In contrast, 4-chloro-3-hydroxyanthranilate did not reduce accumulation of L-[13C6]kynurenine and [13C6]kynurenate. 6-Chlorotryptophan and 4-chloro-3-hydroxyanthranilate are useful tools to manipulate concentrations of quinolinate and kynurenate in the animal models of neurologic disease to evaluate physiological roles of these neuroactive metabolites.
 ...
PMID:Metabolism of L-tryptophan to kynurenate and quinolinate in the central nervous system: effects of 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate. 759 10

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.
 ...
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

The cytotoxic effects of the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 were studied in human CHP100 neuroblastoma cell cultures. Incubation of neuroblastoma cultures with gp120 (1 pM-10 nM) induces cell death which is not concentration-related. The significant cell death evoked by 10 pM gp120 was prevented by neutralization of the viral protein with a monoclonal anti-gp120 (IgG) antibody. In addition, gp120-induced cytotoxicity was inhibited by [DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] (CGP37849; 100 microM), [(+/-)-3R*, 4as*, 6R*, 8aR*-6-(phosphonomethyl) decahydro-isoquinoline-3-carboxylic acid] (LY274614; 100 microM), MK801 (dizocilpine; 200 nM) and 7-chloro kynurenic acid (100 microM), selective antagonists of the NMDA receptor complex; by contrast, (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 100 microM), a non-NMDA antagonist, was ineffective. Prevention of the lethality elicited by the HIV-1 coat protein was also obtained by incubating neuroblastoma cells with gp120 in Ca(2+)-free medium. The lethal effects induced by gp120 involve activation of L-arginine-nitric oxide (NO) pathway since these were prevented by haemoglobin (10 microM), a NO-trapping agent, and by D-arginine (1 mM), the less active enantiomer of the endogenous precursor of NO synthesis. Cytoprotection was also afforded by N omega-nitro-L-arginine methyl ester (L-NAME; 200 microM), an inhibitor of NO synthase, and this was reversed by L-arginine (1 mM). Interestingly, indomethacin and flufenamic acid (10 microM), two inhibitors of cyclooxygenase, protected neuroblastoma cells from death induced by gp120. Furthermore, indomethacin prevented the neuroblastoma cell death evoked by exposure of cultures to sodium nitroprusside (SNP; 0.2-1.6 mM), a NO donor. Finally significant cytotoxic effects were observed after incubation of neuroblastoma cells with prostaglandin E2 (0.1-10 microM). In conclusion, the present data suggest that death of human CHP100 neuroblastoma cells in culture produced by gp120 involves NO and PGE2 production.
 ...
PMID:Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is prevented by NMDA receptor antagonists and inhibitors of nitric oxide and cyclooxygenase. 858 64

To understand the mechanism of interaction of the dopamine D2L receptors with NMDA receptors, we have developed a model by transfecting human neuroblastoma SH-SY5Y cells with the human dopamine D2L receptor gene. In vitro blockade of NMDA receptors by the specific antagonists MK-801 and (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) on human neuroblastoma SH-SY5Y cells expressing human dopamine D2L receptors resulted in a significant increase in the density of D2L receptors without a significant change in receptor affinity. Moreover, the dopamine receptor mRNA level increased by approximately 50% by the blockade of NMDA with MK-801. These results suggest a possible interaction of NMDA and dopamine D2L receptors in neuroblastoma SH-SY5Y cells. This system would serve as an excellent model to study the molecular mechanisms involved in the interaction of these two receptors.
 ...
PMID:Interaction of NMDA and dopamine D2L receptors in human neuroblastoma SH-SY5Y cells. 863 61

In order to clarify the role of cytosolic Ca2+ buffering, a property that in living cells is sustained primarily by high affinity binding proteins, in NMDA receptor-sustained neuron excitotoxicity, cultures of the neuroblastoma line CHP 100 (which is known to express the receptor) were loaded with the chelator BAPTA by incubation with various concentrations (0.03-1 microM) of its acetoxymethylester derivative. The effectiveness of the loading in terms of cytosolic buffering was confirmed by fura-2 measurement experiments in which the [Ca2+]i transients induced by cell exposure to ATP were blunted in the initial peak (up to -75%) and also in the following plateau. When the BAPTA-loaded neuroblastoma cells were exposed to NMDA (1 mM), excitotoxicity was reduced dose-dependently up to almost 70%, while the generation of cGMP was inhibited up to completion. The latter result suggested the possible involvement of nitric oxide in the NMDA-induced excitoxicity, a mechanism confirmed by the dose-dependent inhibitory effect induced by the nitric oxide synthase blocker, L-N-(1-iminoethyl)-ornithine, which protected the cells completely when administered at 300 microM. Flow cytometry analysis of DNA revealed that the mechanism of excitotoxicity in CHP100 cells does not involve apoptosis. We conclude that cytosolic Ca2+ buffering, a property known to vary considerably among neuronal cells and to change in some neurons also during ageing, has a general protective effect. Such a protection appears to take place via the blunting of the glutamate-induced [Ca2+]i responses mediated by the NMDA receptor, with prevention of the ensuing overactivation of nitric oxide synthase and of the irreversible derangement of the ionic homeostasis of the cell.
 ...
PMID:Cytosolic Ca2+ buffering, a cell property that in some neurons markedly decreases during aging, has a protective effect against NMDA/nitric oxide-induced excitotoxicity. 876 26

1. Crude synaptosomes (P2) and synaptosomal membranes were prepared from normal C57/B110 mouse brains and Wistar rats respectively. 2. [3H]Pro binding to mouse brain synaptic membranes was examined in the presence of competitive NMDA antagonist, MK-801, or HA-966. Conversely, the effects of l-proline on [3H]MK-801 binding were also probed. The effects of l-proline on glutamate-medicated [Ca+2]i levels were tested. 3. The authors could not detect any effect of proline on glutamate-mediated [CA+2]i levels using FURA-2 in synaptosomes or neuroblastoma cells. 4. NMDA competitive antagonists, AP-7, CPP, and CGS 19755 inhibit [3H]Pro binding to mouse brain synaptic membranes. 5. MK-801, a NMDA channel blocker, also inhibits [3H]Pro binding, but 200 mM proline is incapable of inhibiting [3H]MK-801 binding. 6. HA-966, a glycine site partial agonist inhibits [3H]Pro binding. Proline has modest effects on [3H]glycine binding.
 ...
PMID:Proline-glutamate interactions in the CNS. 907 63

Sabeluzole was described to have antiischemic, antiepileptic, and cognitive-enhancing properties, and is currently under development for Alzheimer's disease. Recently, it was reported that repeated treatments with sabeluzole protect cultured rat hippocampal neurons against NMDA- and glutamate-induced neurotoxicity. We evaluated the possibility that sabeluzole elicits neuroprotection by acting, either directly or indirectly, on tau proteins. We found that repeated treatments during development of primary cultures of cerebellar granule cells with nanomolar concentrations of sabeluzole resulted in mature cells that were resistant to the excitotoxicity induced by glutamate. Also, sabeluzole treatment specifically prevented the glutamate-induced increase of tau expression without modifying the basal pattern of expression of tau proteins, as shown by measurement of mRNA and protein levels. In human neuroblastoma cell line SH-SY5Y, differentiated by treatment with retinoic acid, doxorubicin increased tau immunoreactivity, and later induced cell death. Both effects were prevented by sabeluzole. Our data indicate that increased tau expression is a common response to different types of cells to neurotoxic agents, and that sabeluzole-induced neuroprotection is functionally associated with the prevention of the injury-mediated increase of tau expression.
 ...
PMID:Priming of cultured neurons with sabeluzole results in long-lasting inhibition of neurotoxin-induced tau expression and cell death. 913 69


1 2 3 4 5 Next >>