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)

1. Addition of 3.5 mM ATP to mouse neuroblastoma Neuro-2A cells results in a selective enhancement of the plasma membrane permeability for Na+ relative to K+, as measured by cation flux measurements and electro-physiological techniques. 2. Addition of 3.5 mM ATP to Neuro-2A cells results in a 70% stimulation of the rate of active K+ -uptake by these cells, partly because of the enhanced plasma membrane permeability for Na+. Under these conditions the pumping activity of the Neuro-2A (Na+ +K+)-ATPase is optimally stimulated with respect to its various substrate ions. 3. External ATP significantly enhances the affinity of the Neuro-2A (Na+ +K+)-ATPase for ouabain, as measured by direct [3H]ouabain-binding studies and by inhibition studies of active K+ uptake. In the presence of 3.5 mM ATP and the absence of external K+ both techniques indicate an apparent dissociation constant for ouabain of 2 X 10(-6)M. Neuro-2A cells contain (3.5 +/- 0.7) X 10(5) ouabain-binding sites per cell, giving rise to an optimal pumping activity of (1.7 +/- 0.4) X 10(-20) mol K+/min per copy of (Na+ +K+)-ATPase at room temperature.
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PMID:Effect of external ATP on the plasma membrane permeability and (Na+ +K+)-ATPase activity of mouse neuroblastoma cells. 628 92

Three clones of neuroblastoma-glioma cells that contain low amounts of calmodulin were selected from the NG108-15 cells after several treatments with high concentrations of chlorpromazine. Purified membranes of the three clones had decreased numbers of both alpha-adrenergic and opiate receptors, monitored with [3H]yohimbine and [3H,D-Ala2]methionine encephalinamide, respectively. No changes were observed in the affinity of these radioactive ligands to the receptors of the selected cells as compared to the parent cells. Addition of bovine brain calmodulin did not affect the binding of [3H,D-Ala2]methionine encephalinamide to the membranes of the selected cells and they had the same number of acetylcholine receptors, determined with 1-quinuclidinyl-[phenyl-4-3H]-benzilate, as the parent NG108-15 cells. The basal ATPase activity in the membranes of the selected cells was 35-50% of the parent cells, with a decreased V value and no significant change in the affinity constant Ka to ATP. Addition of Ca2+ to the purified membranes increased the V of the ATPase in the selected as well as the parent cells but the V of the selected cells remained lower than that of the parent cells. Ca2+ had no effect on the Ka to ATP in either cell type. The Ca2+-dependent ATPase activity of both the parent and the selected cells was also calmodulin-dependent dependent since it was blocked in vitro by chlorpromazine. The co-regulation of opiate and adrenergic receptors and their interaction with calmodulin and Ca2+-ATPase is discussed in view of recent observations indicating biochemical and physiological association between opiates, Ca2+ and adrenergic compounds.
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PMID:A genetic approach to reveal the action of the opiate receptor in selected neuroblastoma-glioma cells. Interaction with alpha-adrenoceptors, calmodulin and Ca2+-ATPase. 629 58

Dibutyryl cyclic AMP and butyrate inhibited growth of S-20 (cholinergic) and NIE-115 (adrenergic) neuroblastoma clones. Both these drugs resulted in a parallel increase of choline acetyltransferase and ATP-citrate lyase activities in S-20 neuroblastoma cells. On the other hand, the increase in tyrosine hydroxylase activity in NIE-115 caused by these drugs was not accompanied by a significant change in ATP-citrate lyase activity. Both dibutyryl cyclic AMP and butyrate caused a decrease in fatty acid synthetase activity in both cell lines. The activities of pyruvate dehydrogenase, citrate synthase, choline acetyltransferase, and lactate dehydrogenase in both S-20 and NIE-115 cells were not significantly influenced by the drugs. ATP-citrate lyases from S-20 and NIE-115 had similar kinetic and immunological properties, and their subunits had the same molecular weight as the rat liver enzyme. These data indicate that the differential regulation of ATP-citrate lyase activity in cholinergic and adrenergic cells does not result from the existence of different molecular forms of the enzyme in these cell lines. They also provide further evidence to support the hypothesis that ATP-citrate lyase activity increases during maturation of normal cholinergic neurons and decreases in noncholinergic cells of the brain.
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PMID:The enzymes of acetyl-CoA metabolism in differentiating cholinergic (s-20) and noncholinergic (NIE-115) neuroblastoma cells. 630 53

The pumping activity of the plasma membrane-bound Na+,K+-ATPase shows considerable variation during the cell cycle of mouse neuroblastoma Neuro-2A cells. Addition of external ATP at millimolar concentrations, which selectively enhances the plasma membrane permeability of Neuro-2A cells for sodium ions, stimulates the Na+,K+-ATPase pumping activity at all phases of the cell cycle from a factor of 1.05 in mitosis up to 2.2 in G1 phase. Determination of the number of Na+,K+-ATPase copies per cell by direct 3H-ouabain binding studies in the presence of external ATP shows a gradual increase in the number of pump sites on passing from mitosis to the late S/G2-phase by approximately a factor of 2. From these data the pumping activity per copy of Na+,K+-ATPase, optimally stimulated with respect to its various substrate ions, has been determined during the various phases of the cell cycle. This optimally stimulated pumping activity per enzyme copy, which is a reflection of the physicochemical state of the plasma membrane, is high in mitosis, almost twofold lower in early G1 phase, and increases gradually again during the other phases of the cell cycle. This shows that the observed regulation of Na+,K+-ATPase activity during the cell cycle is caused by a combination of three independent factors--namely variation in intracellular substrate availability (Na+), changes in number of enzyme copies per cell, and modulation of the plasma membrane environment of the protein molecules. The modulation of the optimal pumping activity per enzyme copy shows a good correlation (rho = 0.96) with the known modulation of protein lateral mobility during the cell cycle, such that a high protein lateral mobility correlates with a low enzyme activity. It is concluded that changes in plasma membrane properties take place during the Neuro-2A cell cycle that result in changes in the rate of protein lateral diffusion and Na+,K+-ATPase activity in directly correlated way.
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PMID:Membrane regulation of the Na+,K+-ATPase during the neuroblastoma cell cycle: correlation with protein lateral mobility. 630 15

The incorporation of methionine, lysine, and leucine into protein was studied in Ca2+-depleted and Ca2+-restored preparations of C-6 glial tumor cells in minimal medium. Although incorporation proceeded at linear rates in both preparations for more than 1 h and into the same spectrum of proteins, Ca2+-restored cells incorporated amino acid 5- to 10-fold more rapidly than Ca2+-depleted cells. Addition of approximately 200 microM Ca2+ in excess of chelator was required to achieve maximal rates of incorporation in Ca2+-depleted preparations. Stimulation by Ca2+ was rapid in onset (several minutes) and slowly reversible by chelator. Ca2+ was uniquely potent and specific among physiologically occurring cations in conferring such stimulation. Stimulation of amino acid incorporation by Ca2+ occurred over a broad range of pH and osmolarities and was facilitated by Mg2+. The effects of Ca2+ in stimulating amino acid incorporation were not traceable to changes in cAMP metabolism, amino acid uptake, protein catabolism, cell ATP or GTP content, or aminoacylation of transfer RNA. Actinomycin D (1 microgram/ml) did not block the stimulatory effects of Ca2+ although puromycin and cycloheximide did. The stimulatory effects of Ca2+ on protein synthesis were not restricted to C-6 in minimal medium. Protein synthesis was reduced by ethylene glycol bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid 40 to 75% in C-6 glioma, GH3 pituitary tumor, PC-12 adrenal tumor, N2A neuroblastoma, and HeLa cells incubated under simulated growth conditions with various enriched media and sera. Ca2+-depleted S49 lymphoma, CHO ovarian tumor, and normal, dispersed chicken embryo cells in enriched medium responded to Ca2+ restoration with increased rates of protein synthesis as did collagenase-dispersed normal rat liver cells in minimal medium. Protein synthesis in rabbit reticulocyte lysates was also inhibited by Ca2+-selective chelators or by Ca2+ removal by parvalbumin affinity chromatography and the inhibition was reversed by Ca2+. These findings are consistent with the existence of a Ca2+ requirement in the translational phase of protein synthesis in eukaryotic cells.
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PMID:Identification of a Ca2+ requirement for protein synthesis in eukaryotic cells. 631 27

Administration of Escherichia coli endotoxin to NB41A3 neuroblastoma cells in culture produced decreases in 1) intracellular [ATP]/[ADP], 2) flux through pyruvate dehydrogenase (PDH), and 3) total intracellular calcium. These effects were reversible if endotoxin was washed off within 10-15 min, but not if it remained in contact with the cells for 30 min or more. Minor, reversible morphological and functional alterations occurred during the initial phase, but after 30-min exposure to the toxin, the damage was irreversible. A model is proposed in which early, reversible weak binding of endotoxin to the plasma membrane partially blocks inward calcium flux, lowering the intracellular [Ca2+] and consequently the PDH phosphatase activity which activates the PDH complex. If endotoxin is removed at this stage, these processes are reversed and the cell recovers. If not, the toxin becomes irreversibly incorporated into the cell with consequent damage to the plasma membrane and organelles, which leads to massive ion movements resulting in cellular hydration with ultimate disruption of mitochondria and cell death.
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PMID:Cellular effects of endotoxin in vitro. II. Reversibility of endotoxic damage. 635 30

Intramitochondrial substrate metabolism was examined in cultured neuroblastoma NB41A3 cells exposed to endotoxin in order to elucidate possible causes for the changes in [ATP]/[ADP][Pi] and [NAD+]/[NADH] reported by us previously in these cells [1]. Flux through pyruvate dehydrogenase (PDH), measured with [1-14C]-pyruvate, was inhibited by 54% within 10 min in endotoxin-treated cells (0.99 nmol/min/mg dry wt vs 0.46 nmol/min/mg dry wt). In contrast, flux through 2-oxoglutarate dehydrogenase, measured with [1-14C]-glutamate was unaltered (0.79 nmol/min/mg dry wt). Dichloroacetate, an inhibitor of PDH kinase, restored flux through PDH to control levels. In endotoxin-treated cells, only 44% of the total PDH complex was in the active (nonphosphorylated) form as compared to 72% in control cells. Equilibrium uptake studies with 45Ca2+ and atomic absorption measurements showed that intracellular [Ca2+] in endotoxin-treated cells was about 20% lower than in control cells. It is postulated that binding of endotoxin to the plasma membrane triggers a sequence of events that lead to an initial decline in intracellular calcium concentration and that this latter event may be responsible for the inhibition of PDH phosphatase and consequent conversion of the complex to its inactive phosphorylated form.
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PMID:Cellular effects of endotoxin in vitro. I. Effect of endotoxin on mitochondrial substrate metabolism and intracellular calcium. 635 31

The effect of dihydroergocristine on energy metabolism was studied in the isolated perfused rat brain affected by ischemia and in cultivated C-1300 neuroblastoma cells deprived of oxygen and glucose. Creatine phosphate, ATP, ADP, AMP, glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate were measured enzymatically. After a perfusion period of 30 min, the cortex of the isolated perfused rat brain exhibited an energy state not different from that in vivo. Dihydroergocristine added to the perfusion medium (5 mumol/L) did not influence these substrate levels under normal perfusion conditions. However, this drug was able to retard the breakdown of high-energy phosphates during ischemia and to accelerate the restoration of the energy state during the postischemic reperfusion period. The perfusion rate was not changed by the drug, and therefore it was assumed that dihydroergocristine could act directly on cell metabolism. This view was supported by the results obtained from experiments using cultivated N-2a neuroblastoma cells. These cells were incubated in a buffered salt solution deprived of glucose and oxygen for 15 min. Under these conditions, dihydroergocristine (2 mumol/L) added to the incubation medium caused changes in the concentrations or the high-energy phosphates similar to those in the isolated brain preparation: It increased the ATP concentration and decreased the ADP concentration significantly.
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PMID:Effect of dihydroergocristine on energy metabolism studied in the isolated perfused rat brain affected by ischemia and in neuroblastoma cells deprived of oxygen and glucose. 643 25

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

In vitro assay of the adenylate cyclase of NB41A neuroblastoma cells in the presence of increasing concentrations of MnCl2 suggested that the enzyme is modulated by both high- and low-affinity sites for manganese. MnCl2 in a concentration of 1 microM significantly stimulated adenylate cyclase activity, but increasing the concentration of manganese to 3 microM or 10 microM had no further effect. Raising MnCl2 to 0.1 or 1 mM, however, further stimulated enzyme activity. In addition to differences in affinity for manganese, the two classes of binding sites may be distinguished by differences in their interaction with other agents that affect adenylate cyclase activity. Millimolar manganese and magnesium appeared to compete for a common site on the enzyme and the effect of manganese in this range and the effect of guanyl nucleotide were synergistic. In contrast, the stimulation of activity by micromolar manganese appeared to be additive to the effects of either increasing magnesium or the addition of guanyl nucleotide to the assay media. Comparison of the substrate dependency of the reaction measured in the presence and absence of manganese suggests that the stimulation of adenylate cyclase activity involves increases in both the apparent Vmax of the reaction and the affinity for ATP. The results raise the possibility that the interaction of Mn2+ may play a role in the modulation of adenylate cyclase in vivo.
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PMID:Interaction of manganese with NB41A neuroblastoma adenylate cyclase. 683 39


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