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)

The contribution of the changes in the diffuse double layer potential (surface potential) to the resting membrane potential of the mouse neuroblastoma (N-18 clone) was estimated with the use of fluorescent dyes and from the shift of the threshold potential of the Ca-spike. The membrane potential monitored by Rhodamine 6G was unchanged with variations of external K+ concentration [( K+]o) below about 10 mM, and changed linearly with log [K+]o above this concentration, similar to the changes observed with a microelectrode. This result indicates that the independence of the membrane potential of [K+]o at low [K+]o is not brought about by the artifacts caused by insertion of a microelectrode into the cell. The changes in the surface potential in response to various polyvalent cations (Mg2+, Ca2+, Mn2+, Cd2+ and La3+) were monitored by the fluorescence of ANS. The behavior of the surface potential thus observed was closely correlated with that of the membrane potential for the respective polyvalent cations. The surface potential changes in response to increase in [Ca2+]o from 1.8 to 100 mM and in [Mg2+]o from 0.8 to 100 mM were 88% and 85% in magnitude compared with the corresponding changes in the membrane potential, respectively. The effect of variation of [Ca2+]o on the threshold potential of the Ca-spike was compared with that of [Ca2+]o on the resting membrane potential. The magnitude of the surface potential change determined by the shift of the threshold potential was comparable to the magnitude of the membrane potential change. The results in the present study suggest that the surface potential change produced at the membrane surface of N-18 cells is detected as a transmembrane potential change without a large reduction in magnitude.
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PMID:Contribution of surface potential to resting potential in mouse neuroblastoma cells: estimation with fluorescent dyes and from shift of threshold potential for Ca-spike. 632 48

The metabolism of Ca2+ was studied in a neuronal model system, the clonal mouse neuroblastoma x rat glioma hybrid cell line 108CC5. 1. Homogenates of the hybrid cells exhibit a specific activity of Ca2+-ATPase considerably higher than that of homogenates of the parental cells. 2. Uptake and release of 45Ca2+ by the hybrid cells display two and three distinct phases, respectively, and indicate that 40--50% of the cell-associated Ca2+ is located at the cell surface. 3. The influx of 45Ca2+ is insignificantly affected by Mg2+ or Na+, slightly diminished by Ba2+ or Sr2+, strongly inhibited by La3+, Co2+ or prenylamine, and considerably enhanced by high (i.e., depolarizing) concentrations of K+. The efflux of 45Ca2+ is reduced by La3+. 4. The hybrid cells tend to maintain Ca2+ homeostasis with an overall cellular Ca2+ concentration of 0.5--0.7 mM. At 1.8 mM Ca2+ in the medium this implies the necessity of an extrusion pump in the plasma membrane. 5. A reduction in the hybrid cells of the level of ATP is paralleled by a decline in the content of Ca2+. This can only be explained by the existence of energy-dependent intracellular Ca2+ stores that effectively compete for Ca2+ with a Ca2+ pump located in the plasma membrane. The internal stores are not identical with the mitochondria because mitochondrial inhibitors hardly change Ca2+ metabolism. 6. Micromolar concentrations of the ionophore A23187 can switch off the internal Ca2+ stores without affecting considerably the influx of Ca2+ through the plasma membrane. 7. With switched-off Ca2+ stores it is possible to increase the cellular Ca2+ content distinctly and to bring it back again to the control values in an ATP-dependent manner, i.e. to demonstrate the action of a Ca2+-extrusion pump in the plasma membrane. 8. Under some conditions active extrusion of Ca2+ depends not only on ATP but also on the presence of extracellular Na+. 9. Similar results as with hybrid cells are also obtained with rat glioma cells. The methodology of combining energy deprivation with the application of the ionophore A23187 is possibly generally applicable to obtain insight into the Ca2+ metabolism of various cell types.
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PMID:Uptake and energy-dependent extrusion of calcium in neural cells in culture. 644 79

Na+ has been implicated as a requirement for the inhibition of adenylate cyclase by hormones and neurotransmitters. This study examines effects of salt concentration on neuroblastoma plasma membranes that occur in the absence of an inhibitory hormone. The adenylate cyclase response to stimulatory agonists (GTP plus PGE1 (3), PGI2 or PGE2) was influenced by NaCl. As the [NaCl] increased to 150 mM, an increase in maximal activity and a decrease in apparent affinity was observed. At concentrations above 150 mM, NaCl decreased prostaglandin affinity and progressively decreased maximal activation. The GTP requirement was not altered by 30 or 150 mM NaCl in the presence of PGE1 or PGI2. The rate of Gpp(NH)p stimulated activity increased as the [NaCl] was increased in the assay. This increased rate was conserved when membranes activated in the presence of Gpp(NH)p and NaCl were reassayed in the absence of guanine nucleotide or salt. The salt evoked rate increase was proportionally greater at submaximal MgCl2 concentrations. The concentration requirement for Mg2+ was reduced by salt for adenylate cyclase in the presence of GTP or Gpp(NH)p. However, the enzyme stimulated by hormone exhibited a Mg2+ requirement that was low in the absence of salt and could not be further reduced by increased [NaCl]. Alternative monovalent cations (150 mM Li+, K+, Cs+, but not choline or tetramethylammonium) and anions (SO4=) substituted for NaCl. The observed effects were reversible upon washing the membranes and neither ouabain nor tetrodotoxin altered the response. These effects may result from a conformational alteration of a protein particularly sensitive to neutral salts in the assay.
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PMID:Effects of NaCl concentration on adenylate cyclase regulation by prostaglandins and guanine nucleotides. 675 90

Kinetic analyses were made on intracellular Na+-dependent Ca2+ uptake by myocardial cells and neuroblastoma cells (N-18 strain) in culture. Cells loaded with various concentrations of Na+ could be prepared by incubating them in Ca2+-free medium containing various concentrations of Na+. Cells pre-loaded with various concentrations of Na+ were incubated in medium containing Ca2+ and 45Ca. The resulting 45Ca uptake by the two types of cell depended greatly on the initial intracellular concentrations of Na+. Lineweaver-Burk plots of the initial rate of Ca2+ uptake against the external concentration of Ca2+ fitted well to straight lines obtained by linear regression (r greater than 0.95). This result shows that Ca2+ uptake by the two types of cell was achieved by a carrier-mediated transport system. This Na+-dependent Ca2+ uptake was accompanied by Na+ release and the ratio of Na+ release to Ca2+ uptake was close to 3 : 1. A comparison of the kinetic data between myocardial cells and N-18 cells suggested that N-18 cells possess a carrier showing the same properties as that of myocardial cells, i.e.: (1) a similar dependency on the intracellular concentration of Na+; (2) the coincidence of the apparent Michaelis constants for Ca2+ (0.1 mM); (3) the similarities of the Ki values for Co2+, Sr2+ and Mg2+ (Co2+ less than Sr2+ less than Mg2+) and (4) a similar dependency on pH. However, the maximal initial rate, V, of N-18 cells was about 1/100 that of myocardial cells. The rate of Na+-dependent Ca2+ uptake by non-excitable cells was much lower than that by myocardial cells.
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PMID:Kinetic studies on sodium-dependent calcium uptake by myocardial cells and neuroblastoma cells in culture. 678 64

The ATP signaling mechanism in neuroblastoma x glioma hybrid NG108-15 cells differentiated by exposure to dibutyryl-cAMP was characterized. In cells loaded with fura-2, ATP rapidly raised the cytosolic Ca2+ concentration ([Ca2+]i); the magnitude of the rise was inversely proportional to the extracellular Na+ concentration. Large increases in cytosolic Na+ concentration, measured with the fluorescent Na+ indicator sodium-binding benzofuran isophthalate, were dose-dependently elicited by ATP. ATP also evoked the entry of ethidium bromide into cells, and this process was inhibited by Mg2+. Inositol-1,4,5-trisphosphate (IP3) generation induced by ATP was totally blocked by removal of extracellular Ca2+, but residual IP3 generation still remained in nondifferentiated cells. In addition, ATP produced a concentration-, time-, and Mg(2+)-dependent biphasic uptake of 45Ca2+. A range of nucleotides and ATP analogues, including CTP, UTP, and GTP, induced only 9-29% of the ATP response. However, adenosine 5'-thiotriphosphate evoked 79% of ATP-induced 45Ca2+ uptake. 45Ca2+ uptake elicited by ATP could be potently blocked by purinoceptor antagonists, but other tested reagents less effectively blocked the action of ATP. When bradykinin was used as an agonist, the [Ca2+]i rise was transient and was insensitive to the extracellular Na+ concentration. Na+ influx, entry of ethidium bromide, and 45Ca2+ uptake were unaffected by bradykinin. Furthermore, bradykinin-evoked IP3 generation was insensitive to extracellular Ca2+. Neither ATP nor bradykinin had any effect on cAMP levels within cells. These data suggest that ATP induces a [Ca2+]i rise in differentiated NG108-15 cells via two distinct Ca2+ influx mechanisms, i.e., a receptor-operated cation channel and pores formed by ATP4-. These mechanisms are distinct from those elicited by bradykinin.
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PMID:Two distinct ATP signaling mechanisms in differentiated neuroblastoma x glioma hybrid NG108-15 cells. 751 80

The changes in ionic permeability induced by the application of alpha-latrotoxin to NG108-15 neuroblastoma x glioma cells were examined using the nystatin perforated-patch technique for whole-cell recording. Complex single channel activity appeared in the plasmalemmas after delays that ranged from 1-20 min in Krebs' solution. The conductance of a channel fluctuated among at least three broad, approximately equispaced bands, the maximum conductance being about 300 pS, and the reversal potential approximately 0 mV. The channels were permeable to Na+, K+, Ca2+ and Mg2+, poorly permeable to glucosamineH+ and Cl-, and were blocked by La3+. The channels stayed fully open in Ca(2+)-free solutions with 4 mM Mg2+, in solutions with no divalent cations and in solutions with 2 mM Ca2+ and 96 mM Mg2+. They opened infrequently if both internal and external Cl- were replaced by glutamate-. If alpha-latrotoxin opened similar channels in nerve terminals, the flux of ions through them could account for the massive release of neurotransmitter induced by the toxin.
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PMID:Alpha-latrotoxin channels in neuroblastoma cells. 751 70

We have investigated the regulation by divalent cations Mg2+, Ca2+ and Mn2+ of the functional activity of the human integrin VLA-1 expressed on neuroblastoma NB100 cells. VLA-1-mediated adhesion of NB100 cells to ligand collagen type I was supported by either mM concentrations of extracellular Mg2+ or microM levels of Mn2+. In contrast, Ca2+ alone did not induce activation of VLA-1 but exerted a potent inhibitory effect on the Mg(2+)-supported cell adhesion. We have also demonstrated that VLA-1 can be directly activated by the stimulatory monoclonal antibody TS2/16 specific for the integrin beta 1 subunit, resulting in effective adhesion of NB100 cells to type I collagen. This study has been possible by using a novel blocking VLA-alpha 1 specific monoclonal antibody, 5E8D9.
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PMID:Functional regulation of the human integrin VLA-1 (CD49a/CD29) by divalent cations and stimulatory beta 1 antibodies. 751 98

Cell-adhesion activity of the bovine propolypeptide of von Willebrand factor (pp-vWF) was assessed by means of an in vitro assay with several cell lines of both normal and tumor-cell origin. pp-vWF promoted adhesion and spreading of B16 mouse melanoma cells and G-361 human melanoma cells. However, it could not induce adhesion of any other cell lines tested including endothelial cells, normal fibroblasts, and tumor cells of sarcoma, carcinoma, neuroblastoma and leukemia origin. A monospecific polyclonal antibody against pp-vWF, but not against fibronectin, laminin, and von Willebrand factor (vWF), completely blocked the pp-vWF-mediated adhesion, indicating that the cell adhesion was due to the pp-vWF molecule and not due to possible contamination of these three well-known adhesive proteins. The cell-adhesion activity was also observed with human pp-vWF and, furthermore, the adhesion to both bovine and human pp-vWF was not affected by a peptide containing the Arg-Gly-Asp sequence while the peptide abolished the cell adhesion to vWF. The adhesion was completely dependent on Mg2+ and inhibited by Ca2+. Inhibition by an anti-(beta 1 integrin) mAb (4B4) indicates that the receptor for this protein belongs to the beta 1-integrin family. A monoclonal antibody (TC4) among several antibodies directed against bovine pp-vWF inhibited the B16 adhesion to immobilized pp-vWF. The epitope for this monoclonal antibody lies in a central 8-kDa portion of pp-vWF, suggesting that this region is important for the cell-adhesion activity. This idea was supported by the finding that purified 8-kDa fragment promoted adhesion of B16 cells in a concentration-dependent manner. As pp-vWF shows unique cell-type specificity in its adhesion activity, which is completely different from that of fibronectin, laminin, vWF and collagen, it may be a novel type of adhesive glycoprotein that utilizes a beta 1-integrin receptor.
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PMID:Beta 1-integrin-mediated adhesion of melanoma cells to the propolypeptide of von Willebrand factor. 751 67

Because of the importance of collagens in mediating cell-substrate interactions and the association of collagens with neural recognition molecules in the peripheral nervous system, the ability of neural recognition molecules to modify the substrate properties of collagens, in particular collagen type I, for cell adhesion was determined. Two cell lines, the N2A neuroblastoma and PC12 pheochromocytoma, were investigated for their capacity to adhere to different collagen types in the absence or presence of several neural recognition molecules. Adhesion of N2A or PC12 cells and membrane vesicles from PC12 cells to collagen type I was reduced when the collagen had been preincubated prior to its application as substrate with the extracellular domain of myelin-associated glycoprotein (s-MAG) or, as control, fibroblast tenascin-C (F-tenascin). In mixture with other collagen types, s-MAG was only able to reduce the adhesiveness of collagen types III and V, but not of collagen types II and IV. F-tenascin reduced the adhesiveness of all collagen types tested. In contrast to F-tenascin, s-MAG had to be present during fibrillogenesis to exert its effect, indicating that it must be coassembled into the collagen fibril to block the binding site. Cell adhesion to collagen type I was dependent on Mg2+ or Mn2+ and inhibited by a monoclonal antibody to the alpha 1 integrin subunit. The combined observations indicate that s-MAG and F-tenascin interfere with cell binding, most probably by modifying the integrin binding site, and that the two molecules act by different mechanisms, both leading to reduction of adhesion.
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PMID:Recognition molecules myelin-associated glycoprotein and tenascin-C inhibit integrin-mediated adhesion of neural cells to collagen. 754 51

The molecular events associated with beta-amyloid-induced neuronal injury remain incompletely characterized. Using a substantia nigra/neuroblastoma hybrid cell line (MES 23.5) synthetic beta-amyloid 1-40 induced a time and dose-dependent apoptotic cell death which was characterized by cell shrinkage and fragmentation of DNA, and was inhibited by aurintricarboxylic acid (ATA), and cycloheximide (CHX). Following beta-amyloid 1-40 treatment, cyclic GMP, an index of NO synthesis, was increased in MES 23.5 cells. The NO scavenger hemoglobin, as well as the NO synthase inhibitors NG-monomethyl-L-arginine acetate (L-NMMA) and L-N5-(1-iminoethyl)ornithine hydrochloride (L-NI0) attenuated such increases. These same inhibitors and scavengers also significantly prevented cytotoxicity. beta-Amyloid also induced an early and transient increase in intracellular calcium as monitored with laser scanning confocal microscopy and Fluo-3 imaging. These induced calcium transients could be significantly blocked by the N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801. Pretreatment with MK-801 or removal of extracellular Ca2+ also reduced beta-amyloid-induced NO production and neurotoxicity. Furthermore, beta-amyloid neurotoxicity was greatly enhanced in the absence of Mg2+ or in the presence of glutamate or NMDA. These data suggest that beta-amyloid can lead to apoptotic cell death through a NO mediated process possibly triggered by Ca2+ entry through activated NMDA-gated channels.
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PMID:Cell death induced by beta-amyloid 1-40 in MES 23.5 hybrid clone: the role of nitric oxide and NMDA-gated channel activation leading to apoptosis. 758 71


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