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

Lead exposure has devastating effects on the developing nervous system, and has been implicated in variety of behavioral and cognitive deficits as well as neural morphological abnormalities. Since lead impacts many calcium-dependent processes, one likely mechanism of lead toxicity is its disruption of calcium dependent processes, among which is neuronal differentiation. We investigated the effects of inorganic lead on survival and several parameters of differentiation of cultured neurons. Three different cell types were used: Rat hippocampal neurons (a primary CNS cell type), B50 rat neuroblastoma cells (a transformed CNS-derived cell line), and N1E-115 mouse neuroblastoma cells (a transformed peripherally-derived cell line). Lead concentrations ranged from low nM to 1 mM. Lead effects differed considerably among the three cell types, with B50 cells least affected. Lead effects were generally multimodal, with fewest effects observed at intermediate concentrations. Lead inhibited neurite initiation in hippocampal neurons, but stimulated initiation in N1E-115 cells. In those cells that differentiated, lead increased dendrite numbers in hippocampal neurons and neurite numbers in N1E-115 cells. Lead exposure increased both the length and the degree of branching of axons in hippocampal neurons and the length of neurites in N1E-115 cells. We hypothesize that lead impacts multiple regulatory processes that influence neuron survival and differentiation, and that its effects show differing dose-dependencies. The differing responses of the different cell types to lead suggests that differentiation may be regulated in different ways by the three types of cells. Alternatively, or additionally, the cell types may differ in their ability to compensate for, sequester, or expel lead.
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PMID:Effects of inorganic lead on the differentiation and growth of cultured hippocampal and neuroblastoma cells. 166 May 84

Treatment of three neuroblastoma cell types in culture with neuraminidase resulted in enhanced neurite outgrowth. These included the mouse Neuro-2A and rat B104 and B50 lines. The morphological changes depended on the presence of exogenous Ca2+ and were accompanied by modest but statistically significant increases in 45Ca2+ influx. Neuraminidase-stimulated neuritogenesis was blocked by the B subunit of cholera toxin (cholera B) and anti-GM1 antibody, a finding suggesting the effect was due to an increased amount of GM1 on the cell surface. Cholera B also blocked the increase in 45Ca2+ influx. The mouse N1A-103 line, previously characterized as "neurite minus," did not respond to neuraminidase with either neurite outgrowth or enhanced Ca2+ influx. These results point to an influence of GM1 on neuritogenesis in cells with differentiation potential and suggest a mechanism involving modulation of Ca2+ flux.
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PMID:Stimulation of neurite outgrowth in neuroblastoma cells by neuraminidase: putative role of GM1 ganglioside in differentiation. 198 26

Inositol uptake was studied in the rat CNS neuroblastoma B50 cell line. Eadie-Hofstee analysis of the uptake pattern reveals two defined modes of inositol entry into the cell. The high-affinity uptake component requires the presence of extracellular sodium and is inhibited by phloridzin. Analysis of the uptake velocities of the high-affinity uptake component provided the following apparent kinetic parameters: Km = 13.7 microM and Vmax = 14.7 pmol/mg of protein/min (without correcting for residual diffusion) and Km = 12.9 microM and Vmax = 12.3 pmol/mg of protein/min (with correction). At physiological concentrations, the high-affinity transport process contributes approximately 70% to total uptake; the remainder is due to a low-affinity diffusion-like process. Uptake inhibition studies reveal that the uptake process is sensitive to ouabain, amiloride, and dichlorobenzamil inhibition but relatively insensitive to cytochalasin B or phloretin. When neuroblastoma B50 cells are induced to differentiate morphologically with high extracellular calcium or with dibutyryl cyclic AMP, a significant decrease in inositol uptake is observed. The dibutyryl cyclic AMP-mediated inhibition of uptake affects only the high-affinity uptake component and is noncompetitive in nature. The high extracellular calcium-mediated inhibition is less specific; it involves "disappearance" of the high-affinity process, some inhibition of the low-affinity process, and an increase of inositol efflux. The significance of these observations is discussed in the context of neuroblastoma B50 cell differentiation.
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PMID:Inositol metabolism during neuroblastoma B50 cell differentiation: effects of differentiating agents on inositol uptake. 216 74

Previous work demonstrated two stimulatory effects of methyl mercury on nucleic acid synthesis: (1) in isolated nuclei, methyl mercury stimulates RNA synthesis which is catalyzed by RNA polymerase II [Frenkel and Randles, J. Biol. Chem. 257, 6275-6279 (1982)]. (2) Brief exposure of purified DNA to methyl mercury increases the rate of its transcription by purified RNA polymerase II [Frenkel, Cain, and Chao, Biochem. Biophys. Res. Commun. 127, 849-856 (1985)]. The latter effect was considered as a possible mechanism of the former. Two lines of evidence are presented here which demonstrate that the latter effect is not a sufficient explanation for the former. (1) Mercuric perchlorate has been found to increase the rate of DNA transcription by purified polymerase and the template properties of the mercuric perchlorate-exposed DNA have been found to resemble those of methyl mercury-exposed DNA. Nevertheless, mercuric perchlorate has been shown not to stimulate RNA synthesis in isolated HeLa nuclei. (2) In isolated nuclei of the B50 rat neuroblastoma cell line, RNA synthesis has been found to be stimulated only minimally by methyl mercury. Nevertheless, RNA polymerase II purified from the B50 cells has been found to transcribe methyl mercury-exposed DNA at a higher rate than unexposed control DNA.
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PMID:The enhanced rate of transcription of methyl mercury-exposed DNA by RNA polymerase is not sufficient to explain the stimulatory effect of methyl mercury on RNA synthesis in isolated nuclei. 244 20

The rat CNS neuroblastoma B50 cell line is known to differentiate on addition of 1 mM dibutyryl cyclic AMP or on withdrawal of serum. In this report it is shown that high levels of extracellular calcium (10-25 mM) cause neurite extension, an important component of morphological differentiation. Stimulation of calcium influx with the ionophore A 23187 or blockade of calcium efflux with lanthanum are less efficient than extracellular calcium in stimulating neurite extension. These data suggest that intracellular calcium is not sufficient to cause full expression of a calcium-dependent differentiated state. Furthermore, phosphatidylinositol turnover is sharply altered as early as 1 h after addition of calcium to the medium while cyclic nucleotide levels remain unaffected. This suggests that activation of the phosphatidylinositol second-messenger system by calcium at the level of the cell membrane is the initial step in the cascade of events leading to neurite extension. Later events include a decrease in DNA synthesis (6-10 h after addition of calcium), and increase in intracellular calcium levels (12-24 h after calcium addition) concurrent with neurite extension. The intracellular increase in calcium levels is facilitated by synergistic action of 1 mM dibutyryl cyclic AMP with high external calcium (10-25 mM). This combined treatment results in a more complex pattern of neurite formation characterized by many synaptic-like junctions; this pattern is not obtained when either dibutyryl cyclic AMP or calcium is used as sole inducer.
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PMID:Extracellular calcium-induced neuroblastoma cell differentiation: involvement of phosphatidylinositol turnover. 300 98

1. In nuclei isolated from cells of the B50 rat neuroblastoma line the stimulatory effect of methyl mercury on alpha-amanitin-sensitive RNA synthesis is very much reduced compared to the stimulatory effect in HeLa nuclei (see: Frenkel G. D. and Randles K. (1982) Specific stimulation of alpha-amanitin-sensitive RNA synthesis in isolated HeLa nuclei by methyl mercury. J. biol. Chem. 257, 6275-6279). 2. The stimulatory effect of another mercury compound, p-hydroxymercuribenzoate, was also much less pronounced in the B50 nuclei. 3. Similar results were obtained with nuclei isolated from B50 cells which had been induced to differentiate by exposure to dibutaryl cyclic AMP. 4. Nuclei isolated from cells of another rat neuroblastoma line (B35), and nuclei from cells of a human neuroblastoma line both exhibited levels of stimulation similar to that of HeLa nuclei. 5. The B50 and HeLa cells were also compared as to their sensitivity to other effects of methyl mercury.
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PMID:A cell line with decreased sensitivity to the methyl mercury-induced stimulation of alpha-amanitin sensitive RNA synthesis in isolated nuclei. 323 25

A number of neural and nonneural tumor cell lines of rat and human origin were assayed for neuron-specific enolase (NSE) by radioimmunoassay. Most neural tumor cell lines had appreciably higher levels of NSE than did the nonneural tumor cell lines, the highest levels being found in two anaplastic rat glioma lines ( F98 and T24). These two lines contained more than twice the amount of NSE found in a rat pheochromocytoma line (PC12) and in neuroblastoma lines derived from rats ( B35 and B50 ) or humans (IMR-32 and SHSY - 5Y ). Several of the rat glioma and schwannoma lines were inoculated intracerebrally into syngeneic rats. In the resulting tumors, NSE was demonstrable by immunohistochemistry only in those from the F98 and T24 cell lines. A number of ethylnitrosourea-induced rat tumors were also examined immunohistochemically for NSE: NSE was demonstrated in three anaplastic gliomas; three astrocytomas; and two mixed gliomas. Reactive astrocytes were also positive. Fibroadenomas of apocrine and mammary glands in rats were weakly positive, but other extraneural tumors tested were negative. Since normal neuronal elements, axonal swellings, and amine precursor uptake and decarboxylation cells are strongly positive for NSE, whereas glia and most other normal cells are negative, we hypothesize that the elevated metabolic demands imposed on neoplastic and reactive glial cells and on some extraneural tumors necessitate the opening up of metabolic pathways that are normally operative only in neurons and neuroendocrine cells, therefore resulting in the synthesis of the more stable neuron-specific form of enolase.
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PMID:Immunoradiometric and immunohistochemical demonstration of neuron-specific enolase in experimental rat gliomas. 672 96

1. The accumulation of cyclic AMP stimulated by salmeterol, a long-acting beta 2-adrenoceptor agonist and by isoprenaline, a non-selective beta-adrenoceptor agonist have been compared in the B50 neuroblastoma cell line. 2. Salmeterol produced a concentration-dependent increase in the accumulation of total [3H]-cyclic AMP in B50 cells yielding an EC50 value of 37 nM which was lower than that obtained with isoprenaline (294 nM). The maximum response to salmeterol was only 46% of that obtained with isoprenaline. 3. The beta 2-adrenoceptor antagonist, ICI 118551, inhibited the responses to both salmeterol (apparent KD 2.2 nM) and isoprenaline (apparent KD 1.6 nM). However, the beta 1-adrenoceptor antagonist, atenolol, produced no significant effect at concentrations up to 100 microM. 4. Salmeterol (1 microM) changed the concentration-response curve of isoprenaline in the manner of a partial agonist interacting with a full agonist. The KD of salmeterol obtained from the interaction was 55.6 nM. 5. Whereas salmeterol has a slow onset of action in airway smooth muscle compared to other beta 2-adrenoceptor agonists, in B50 monolayers both salmeterol and isoprenaline produced a rapid increase in cyclic AMP accumulation (t1/2 1.1 min and 0.4 min respectively). 6. Despite the existence of cyclic AMP efflux mechanisms that exist in this cell line it was possible to investigate the duration of agonist action by measuring intracellular levels of the second messenger. Replacement of drug-containing medium with fresh buffer led to a rapid reduction in intracellular levels of cyclic AMP in isoprenaline-stimulated cells whereas cyclic AMP accumulation was sustained for much longer periods in salmeterol-stimulated cells. However, the persistent action of salmeterol could be reversed by the addition of a beta2-selective antagonist.7. These results confirm that salmeterol has a high affinity, but low efficacy (relative to isoprenaline) for beta2-adrenoceptors coupled to cyclic AMP accumulation and that the drug persists at its site of action for long periods in the B50 neuronal cell line.
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PMID:Salmeterol, a long-acting beta 2-adrenoceptor agonist mediating cyclic AMP accumulation in a neuronal cell line. 790 76

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

The study of oxygen radical generation and effects during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) metabolism was undertaken in an in vitro test system. Three neurochemically discrete neuronal cell lines, B50 (cholinergic) and B65 rat cell lines and SKNSH human neuroblastoma (both catecholaminergic), were exposed to MPTP (0-200 microM). Parallel experiments were performed using reagent H2O2, an intermediate which may be generated during MPTP metabolism, to determine whether MPTP and H2O2 had any selectivity of toxicity and whether the mechanisms of cell death were similar. MPTP toxicity was shown to be reduced by monoamine oxidase B inhibitors, pargyline (P < 0.01) and selegiline (P < 0.05), indicating that toxicity was due to metabolism of MPTP rather than the parent compound. Cytotoxicity was also decreased in the presence of antioxidants, most notably in the presence of superoxide dismutase and catalase together (P < 0.01), suggesting that reactive oxygen species (ROS) play a role in MPTP-induced cell death. Attempts to determine the intracellular target for oxidative attack did not identify significant levels of lipid peroxidation products, but did demonstrate nucleoid expansion, possibly the result of double stranded DNA breaks induced by ROS.
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PMID:An investigation into the role of reactive oxygen species in the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity using neuronal cell lines. 845 68


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