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

Calcineurin is a calcium/calmodulin-regulated protein phosphatase. By using enzyme-immunoassay and immunocytochemistry with an affinity-purified specific antibody to this protein, we have found that calcineurin is expressed in the central and peripheral neuroendocrine cells, also termed amine precursor uptake and decarboxylation cells. In addition, calcineurin immunoreactivity was found in the central neuroendocrine neoplasms such as pineocytoma, olfactory neuroblastoma and paraganglioma. The present findings indicate that the activity of phosphatase regulated by calcium and calmodulin is involved in neuroendocrine functions, and that the enzyme can be useful for the identification and characterization of neuroendocrine cell tumors.
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PMID:Calcineurin, a calcium/calmodulin-regulated protein phosphatase, in mammalian neuroendocrine cells and neoplasms. 133 5

High-threshold (HVA) Ca2+ channels of human neuroblastoma IMR32 cells were effectively inhibited by noradrenaline. At potentials between -20 mV and +10 mV, micromolar concentrations of noradrenaline induced a 50%-70% depression of HVA Ba2+ currents and a prolongation of their activation kinetics. Both effects were relieved at more positive voltages or by applying strong conditioning pre-pulses (facilitation). Facilitation restored the rapid activation of HVA channels and recruited about 80% of the noradrenaline-inhibited channels at rest. Re-inhibition of Ca2+ channels after facilitation was slow (tau r 36-45 ms) and voltage-independent between -30 mV and -90 mV. The inhibitory action of noradrenaline was dose-dependent (IC50 = 84 nM), mediated by alpha 2-adrenergic receptors and selective for omega-conotoxin-sensitive Ca2+ channels, which represent the majority of HVA channels expressed by IMR32 cells. The action of noradrenaline was mimicked by intracellular applications of GTP[gamma S] and prevented by GDP[beta S] or by pre-incubation with pertussis toxin. The time course of noradrenaline inhibition measured during fast application (onset) and wash-out (offset) of the drug were independent of saturating agonist concentrations (10-50 microM) and developed with mean time constants of 0.56 s (tau on) and 3.6 s (tau off) respectively. The data could be simulated by a kinetic model in which a G protein is assumed to modify directly the voltage-dependent gating of Ca2+ channels. Noradrenaline-modified channels are mostly inhibited at rest and can be recruited in a steep voltage-dependent manner with increasing voltages.
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PMID:Voltage-dependent noradrenergic modulation of omega-conotoxin-sensitive Ca2+ channels in human neuroblastoma IMR32 cells. 133 78

Insulin and insulin-like growth factors are neuroactive peptides. We investigated the effect of insulin-like growth factor I (IGF-I) on Ca2+ channel currents in 108CC15 neuroblastoma x glioma (N x G) cells and a possible role of protein kinase C (PKC). Whereas the native IGF-I enhanced the Ca2+ channel current density in N x G cells, the boiled IGF-I had no effect. The effect of IGF-I occurred after 1-2 h incubation and reversed within 24 h. Ca2+ channel currents recorded in control cells were mainly of a low-threshold fast inactivating type and showed a mean density of 5.9 +/- 0.3 pA/pF. Current density in cells incubated with IGF-I (0.2 micrograms/ml) for 2 h increased to 9.2 +/- 0.8 pA/pF. Ca2+ channel currents in cells treated with IGF-I showed an enhanced amount of a high-threshold slowly inactivating Ca2+ current type sensitive to the dihydropyridine isradipine and the snail toxin omega-conotoxin. The effect of IGF-I was suppressed by coincubation with the PKC inhibitors 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) and staurosporin which were both without effect on current density in control cells. Whereas the inactive phorbol ester phorbol 12-myristate 13-acetate (PMA) failed to modulate Ca2+ channels in N x G cells, stimulation of PKC by the active phorbol ester PMA mimicked the effect of IGF-I. The effects of IGF-I and phorbol ester were not additive. Our data suggest an intracellular mechanism dependent on PKC and we propose a physiological relevance of the observed Ca2+ channel modulation by IGF-I in the neuroactivity of the peptide.
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PMID:Insulin-like growth factor I modulates voltage-dependent Ca2+ channels in neuronal cells. 133 4

The effects of aluminium on inositol phosphate formation were examined in murine neuroblastoma cells labelled with [3H]-myo-inositol. In aluminium-pretreated cells, the bradykinin-triggered inositol triphosphate, IP3, release and the change in intracellular [Ca2+] were appreciably less compared with the control group. Stimulating digitonin-permeabilized cells with non-hydrolyzable guanosine 5'-[gamma-thio]-triphosphate, GTP[S], inositol phosphate formation decreased in the presence of aluminium. A primary target of aluminium toxicity may reside on the guanine nucleotide-binding protein(Gp)/phospholipase C system, at a site different from that of the GTP[S] binding site.
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PMID:Aluminium interferes with signal transduction in neuroblastoma cells. 133 97

The immortalized septal cell line, SN56 B5 G4, generated by the fusion of mouse septal area cells and neuroblastoma cells, was used to determine if nimodipine, an antagonist of voltage sensitive calcium 'L' channels, might act in a neuroprotective fashion when intracellular calcium levels were raised by incubation in ouabain and monensin. Fluorescent indicator dyes and the automated spectrofluorometer, the CytoFluor 2300, were used to analyze specific cellular targets and functions affected by ouabain and monensin and possible protection by prior incubation with nimodipine. Ouabain and monensin were used together to create a time- and dose-dependent toxic episode. Increases in the emission intensity of Fluo3-AM demonstrated that the concentration of intracellular calcium was monotonically increased by increasing levels of ouabain-monensin. The calcein-AM fluorescent probe indicated that there were no changes in plasma membrane permeability during the toxic episode. Lysosomal integrity decreased as indicated by decreases in neutral red retention. The concentration of free radicals increased as shown by the increase in emission intensity of 2',7'-dichlorfluorescein. Nimodipine pretreatment of the cells incubated with ouabain and monensin resulted in apparent protection of lysosomes and a reduction in the level of free radicals. While nimodipine, by itself, produced a small decrease in intracellular calcium, it actually augmented the ouabain-monensin induced increase in intracellular calcium. The data suggest that in immortalized septal cells, (a) nimodipine offers protection to certain of the responses induced by ouabain-monensin, (b) the protection offered by nimodipine may be independent of antagonism of voltage sensitive calcium channels, and (c) that the protective changes can occur at the same time that intracellular calcium is increasing. These latter observations question the hypothesis that the protection against cell death and dysfunction offered by nimodipine is due solely to maintaining calcium homeostasis.
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PMID:Cellular alterations produced by the experimental increase in intracellular calcium and the nature of protective effects from pretreatment with nimodipine. 133 95

The ability of two enantiomeric fluoro-analogues of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] to mobilize intracellular Ca2+ stores in SH-SY5Y neuroblastoma cells has been investigated. (-)-D-2,2-difluoro-2-deoxy-myo-Ins(1,4,5)P3 [D-2,2-F2-Ins(1,4,5)P3] was a full agonist [EC50 0.21 microM] and slightly less potent than D-Ins(1,4,5)P3 [EC50 0.13 microM]. (+)-L-2,2-F2Ins(1,4,5)P3 was a very poor agonist, confirming the stereospecificity of the Ins(1,4,5)P3 receptor. D-2,2-F2-Ins(1,4,5)P3 mobilized Ca2+ with broadly similar kinetics to Ins(1,4,5)P3 and was a substrate for Ins(1,4,5)P3 3-kinase inhibiting Ins(1,4,5)P3 phosphorylation (apparent Ki = 10.2 microM) but was recognised less well than Ins(1,4,5)P3. L-2,2-F2-Ins(1,4,5)P3 was a potent competitive inhibitor of 3-kinase (Ki = 11.9 microM). Whereas D-2,2-F2-Ins(1,4,5)P3 was a good substrate for Ins(1,4,5)P3 5-phosphatase, L-2,2-F2Ins(1,4,5)P3 was a relatively potent inhibitor (Ki = 19.0 microM).
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PMID:Synthetic D- and L-enantiomers of 2,2-difluoro-2-deoxy-myo-inositol 1,4,5-trisphosphate interact differently with myo-inositol 1,4,5-trisphosphate binding proteins: identification of a potent small molecule 3-kinase inhibitor. 133 23

To elucidate the mechanisms of the intracellular signal transduction elicited with bradykinin in NG108-15 neuroblastoma x glioma hybrid cells, we examined the activation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) by bradykinin stimulation. When the extract of NG108-15 cells was immunoprecipitated with the affinity-purified antibody to brain CaM kinase II, a 50-kDa protein in the immunoprecipitate mainly became autophosphorylated in a Ca2+/calmodulin-dependent manner. The results suggest that the 50-kDa protein is the subunit of CaM kinase II in NG108-15 cells. The Ca2+/calmodulin-independent activity (autonomous activity) of the enzyme increased twice within 10 s by stimulation with 1 microM bradykinin in the cells. The increase in the autonomous activity of the enzyme had two phases: the transient early-peak phase and the long late-plateau phase. The former was abolished by the pretreatment of the cells with 10 mM caffeine or 20 microM BAPTA-AM, and the latter was abolished by the removal of the extracellular Ca2+ with 1 mM EGTA or by the pretreatment with 1 microM nifedipine. Stimulation of 32P-labeled NG108-15 cells with 1 microM bradykinin increased the autophosphorylation of CaM kinase II and this increase was abolished by pretreatment with caffeine or BAPTA-AM. These results suggest that CaM kinase II is activated via the inositol phospholipid signaling pathway induced with bradykinin in NG108-15 cells.
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PMID:Activation of Ca2+/calmodulin-dependent protein kinase II by stimulation with bradykinin in neuroblastoma x glioma hybrid NG108-15 cells. 133 47

Toki-shakuyaku-san (Tsumura TJ-23) is a Chinese medicine which has been used for the treatment of gynecological symptoms in aged women. There are several reports on the usefulness of this drug in the treatment of cognitive disorders. We studied the effects of toki-shakuyaku-san on electrical activity in NG108-15 cells, a cell line of differentiated neuroblastoma x glioma hybrid cells, and on frog neuromuscular transmission. In the hybrid cells, an extract of toki-shakuyaku-san slightly depolarized the membrane potential, and strongly decreased the peak heights of the Na+ and Ca2+ current components of the action potential. The order of potency for NG108-15 cells of the 5 ingredients in toki-shakuyaku-san was soujyutsu >> shakuyaku, takusha, toki, senkyu. In voltage-clamped NG108-15 cells, toki-shakuyaku-san and soujyutsu decreased the Na+, K+, and Ca2+ current components. Toki-shakuyaku-san and soujyutsu also induced an increase in the intracellular calcium concentration. However, toki-shakuyaku-san did not affect neuromuscular transmission in the frog sartorius muscle. The results suggest that the effects of toki-shakuyaku-san on neurons are multiple, and tissue- and species-specific, and its effect derives mainly from soujyutsu.
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PMID:Effects of toki-shakuyaku-san (Tsumura TJ-23) on electrical activity in neuroblastoma cells and frog neuromuscular junctions. 133 88

Signal transduction pathways from bradykinin (BK) receptors were investigated in NG108-15 neuroblastoma x glioma hybrid cells by buffering the intracellular calcium (Ca2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a Ca2+ chelator. BK increased inositol-1,4,5-trisphosphate (Ins(1, 4,5)P3) formation at the same rate in the control and in BAPTA-acetoxy methyl ester (AM)-treated NG108-15 cells. However, a transient increase of intracellular Ca2+ concentrations in response to BK was significantly suppressed in Ca(2+)-buffered hybrid cells. Accordingly the BK-induced outward current was inhibited in BAPTA-AM-treated hybrid cells, while the subsequent inward current associated with a fall in membrane conductance was apparently increased. The initial phase of acetylcholine release from NG108-15 cells in response to BK was markedly inhibited in BAPTA-AM-treated coculture dishes when detected as miniature end-plate potentials of myotubes, though the late phase of acetylcholine secretion was observed. These results indicate that BK induces two distinct responses in NG108-15 cells: Ins(1,4,5)P3-dependent intracellular Ca2+ rise-sensitive and -insensitive components.
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PMID:Dissection of bradykinin-evoked responses by buffering intracellular Ca2+ in neuroblastoma x glioma hybrid NG108-15 cells. 133 34

A study of the intracellular Ca2+ ([Ca2+]i) response of differentiated neuroblastoma x glioma hybrid cells (NG108-15 cell) to enkephalin (EK) was carried out by fura-2 video-imaging. EK alone did not influence [Ca2+]i in single cells. The opioid did, however, induce a marked [Ca2+]i rise, when the cells were incubated with bradykinin (BK) prior to the EK treatment. Such BK-assisted stimulation of the differentiated hybridoma cells by EK was completely abolished by pertussis toxin treatment. These results suggest that in single NG108-15 cells, EK induces Ca2+ mobilization which is assisted by cross-talk between the EK and BK receptor systems via a pertussis toxin-sensitive G protein.
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PMID:Enkephalin induces Ca2+ mobilization in single cells of bradykinin-sensitized differentiated neuroblastoma hybridoma (NG108-15) cells. 133 52


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