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)

The effects of nitrogen bases on the regulation of phospholipid metabolism in neuroblastoma cell cultures were investigated. An increase in the total cellular phospholipids was observed up to 24 h following plating. Addition of monomethyl- and dimethylethanolamine bases resulted in a stimulation of the synthesis of their corresponding phospholipids. The average rates of synthesis of phosphatidylmonomethyl- and phosphatidyldimethylethanolamine were 0.09 and 0.12 nmol/microgram DNA per h, respectively. The labeling patterns of the various phospholipid species from ortho[32P]phosphate have been determined. They suggest that the synthesis of the analogs proceeded entirely via a phosphate mediated pathway rather than through a base exchange mechanism. A number of distinct patterns for the incorporation of bases into acyl-, alkyl- and alkenyl-containing phosphoglyceride species were indicated. The polar head group composition appeared to be intimately related to the type of bond of the hydrocarbon residue.
 ...
PMID:Base stimulation of phospholipid metabolism in neuroblastoma cells. I. Kinetics of incorporation of N-methylated ethanolamine bases. 92 30

C-6 glioma and C-1300 neuroblastoma cells were cultured in thiamine deficient and control media. Thiamine levels, transketolase and pyruvate decarboxylase activities, and high energy phosphate metabolites were all measured in deficient and control cells. Thiamine levels in the deficient cells were found to be below the level of detectability. Pyruvate decarboxylase activity was more susceptible to thiamine deficiency in both cell lines than transketolase. In spite of the large decrease in pyruvate decarboxylase activity, high energy phosphate metabolites were not decreased in either cell line. These data indicate that C-6 glioma and C-1300 neuroblastoma cells have the capacity to maintain normal energy metabolites in the presence of large changes in thiamine levels and thiamine dependent enzyme activity.
 ...
PMID:Glycolytic metabolism in cultured cells of the nervous system. IV. The effects of thiamine deficiency on thiamine levels, metabolites and thiamine-dependent enzymes on the C-6 glioma and C-1300 neuroblastoma cell lines. 100 96

Stimulation of m1 and of m3 muscarinic receptors has previously been shown to increase intracellular cAMP levels in a variety of cells. Although the mechanism underlying this response is not fully understood, it has been hypothesized to be secondary to the IP3-mediated rise in intracellular calcium. In order to determine whether other means of elevating intracellular calcium also raise cAMP levels, we stimulated SK-N-SH human neuroblastoma cells with bradykinin or with maitotoxin. Both of these agents stimulated phospholipase C, stimulated inositol phosphate release and elevated cAMP levels, thus demonstrating that this cAMP response is not unique to muscarinic receptor stimulation.
 ...
PMID:Agents that stimulate phosphoinositide turnover also elevate cAMP in SK-N-SH human neuroblastoma cells. 131 35

To study second messenger synthesis mediated by the cloned rat neurotensin receptor, we derived a cell line stably expressing this receptor. The cDNA clone of this receptor was subcloned into the pcDNA1neo expression vector. This construct was then used to transfect Chinese hamster ovary (CHO)-K1 cells. Colony clones, selected for resistance to antibiotic G-418 sulfate, were isolated and grown separately. Nineteen individual clones were screened for total [3H]neurotensin binding as an indication of neurotensin receptor expression. The clone (CHO-rNTR-10) showing the highest level of specific [3H]neurotensin binding was characterized further. With intact cells, the equilibrium dissociation constant (KD) for specific [3H]neurotensin binding was 18 nM, and the maximal number of binding sites (Bmax) was 900 fmol/mg of protein or 740 fmol/10(6) cells (approximately 4.4 x 10(5) sites on the cellular surface). Whereas the KD was similar to that found in other cellular systems, for example, the murine neuroblastoma clone N1E-115, the Bmax exceeded previously reported values. Incubation of intact CHO-rNTR-10 cells with neurotensin caused the release of inositol phosphates in a dose-dependent manner (EC50 = 3 nM), results indicating that the expressed transfected receptor was functional. Neurotensin did not inhibit cyclic AMP levels stimulated by forskolin. As with other systems, neurotensin (8-13) was more potent than neurotensin Neurotensin-mediated inositol phosphate release is the first report of second messenger synthesis for this receptor expressed in a transfected cell line. These results suggest that the relation between structure and function of the neurotensin receptor can be readily studied in transfected cell lines.
 ...
PMID:The rat neurotensin receptor expressed in Chinese hamster ovary cells mediates the release of inositol phosphates. 132 36

In a SK-N-BE human neuroblastoma cell line the incubation of rubidium (1 and 10 mM) for 24 h significantly increased IP2 formation, whereas it apparently did not affect other inositol phosphates. In comparison to lithium (10 mM), which significantly enhanced inositolmonophosphate and IP2 accumulation following carbamoylcholine (1 mM) stimulation, rubidium at the same concentration, was unable to affect inositol phosphate accumulation. In conclusion, the present experiments show that rubidium, compared with lithium, shows a different profile on phosphoinositide metabolism since its main action is an increase in phosphatidylinositol turnover. These results may have some relevance to the use of rubidium as antidepressant in man.
 ...
PMID:Rubidium shows effects different from lithium on phosphatidylinositol metabolism in a cell line of human neuroblastoma. 133 Aug 42

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.
 ...
PMID:Aluminium interferes with signal transduction in neuroblastoma cells. 133 97

1. Muscarinic but not nicotinic receptor stimulation in SH-SY5Y human neuroblastoma cells induces a concentration-dependent increase in [3H]-inositol phosphate formation and a biphasic increase in [Ca2+]i. The latter involves release from both an intracellular store and Ca2+ entry across the plasma membrane. Here we examine the possibility that this agonist-stimulated Ca2+ entry occurs indirectly, as a consequence of depolarization. 2. Electrophysiological characterization, by whole cell patch-clamp techniques revealed that SH-SY5Y cells possess a tetrodotoxin-sensitive inward sodium current, a dihydropyridine-insensitive calcium current and an outward potassium current which was blocked by tetraethylammonium, 4-aminopyridine and intracellular caesium ions. The outward potassium current showed voltage-dependent activation and inactivation, similar to that seen for A-currents. 3. Application of nicotinic agonists evoked an inward current in cells voltage-clamped at negative holding potentials, but this current rectified, resulting in little or no outward current flow at positive potentials. The mean amplitude at a holding potential of -60 mV was -1.14 nA. Extrapolation of the current-voltage relation gave a reversal potential of +8 mV, indicative of a non-specific cationic permeability. 4. Application of muscarinic agonists had no detectable effect in most of the cells tested. However, in one third of cells studied, a small slowly activating inward current was observed. The mean amplitude of this current at a holding potential of -60 mV was -8.3 pA.5. This study confirms that SH-SY5Y cells possess voltage-dependent sodium, potassium and calcium currents. In addition, these cells are strongly depolarized by nicotinic agonists, which produce little change in [Ca2t]1. On the other hand, muscarinic agonists produce profound changes in [Ca2+1J with only a small inward current (depolarization). The contrasting effects of these two cholinoceptor agonists strongly implies that the Ca2+ entry after muscarinic receptor activation is not primarily due to activation of voltage-dependent calcium channels.
 ...
PMID:Elevation of cytosolic calcium by cholinoceptor agonists in SH-SY5Y human neuroblastoma cells: estimation of the contribution of voltage-dependent currents. 142 73

TMB-8 [8-(NN-diethylamino)-octyl-3,4,5-trimethoxybenzoate] blocks agonist-stimulated release of Ca2+ from intracellular sites in many cell lines and is often used to distinguish between dependence on extracellular and intracellular Ca2+. In N1E-115 neuroblastoma cells, TMB-8 did not alter the resting cytosolic Ca2+ concentration in unstimulated cells, yet phospholipid metabolism was greatly affected. At concentrations of TMB-8 (25-150 microM) that inhibit Ca2+ release, phosphatidylcholine formation was inhibited, whereas synthesis of phosphatidylinositol, phosphatidylglycerol and phosphatidylserine was stimulated. Unlike other cationic amphipathic compounds, TMB-8 did not inhibit phosphatidate phosphatase or enzymes in the pathway from choline to phosphatidylcholine. Choline transport was the major site of action. TMB-8 was a competitive inhibitor (Ki = 10 microM) of low-affinity (Kt = 20 microM) choline transport. When added at the same time as labelled precursor, TMB-8 also decreased cellular uptake of phosphate and inositol, but not that of ethanolamine or serine. In prelabelled cells, continued uptake and incorporation of phosphate and inositol were not affected. Under these conditions phosphatidylinositol synthesis was increased 2-fold and, like the effect on phosphatidylcholine, reached a plateau at 100 microM-TMB-8. Phosphatidylglycerol synthesis increased linearly with TMB-8 concentration to 40-fold stimulation at 150 microM, suggesting a selective effect on synthesis of phosphatidylglycerol from CDP-diacylglycerol. Phosphatidylserine synthesis was also increased up to 3-fold. These Ca(2+)-independent effects limit the use of TMB-8 in studies of cell signalling that involve stimulated phosphatidylinositol and phosphatidylcholine metabolism.
 ...
PMID:Calcium-independent effects of TMB-8. Modification of phospholipid metabolism in neuroblastoma cells by inhibition of choline uptake. 153 May 83

Although beta-D-fucosidase (beta-D-fucoside fucohydrolase, EC 3.2.1.38) has been isolated from various sources, the identity of this enzyme is still not settled. We have purified a specific beta-D-fucosidase in electrophoretically homogeneous form crude extracts of Aspergillus phoenicis by polyethyleneglycol 6000-phosphate buffer aqueous two-phase separation, and successive chromatography on DEAE-Sephadex A-50, hydroxyapatite and Sephadex G-100 columns. The molecular weight of the enzyme was estimated to be 57000 by SDS-polyacrylamide gel electrophoresis and 50000 to 60000 by gel filtration on Sephadex G-100. The enzyme showed optimum coside were 2.4mmol/L, and 1.28 mumol min-1 the pH range 5.5-6.5 and below 35 degrees C. The Km and the Vmax values for pNP-beta-D-fucoside were 2.4mmol/L, and 1.28 mumol.min-1.mg-1 respectively. The enzyme was strongly inhibited by sulfhydryl group reagents, PCMB-NEM and iodoacetate. It was also inhibited by EDC, DEP and NBS. Thus, -SH, -COOH groups, histidyl and tryptophyl residues were essential for enzyme activity. The purified beta-D-fucosidase showed high specificity toward p-nitrophenyl beta-D-fucoside. The enzyme was inhibited by D-fucose and D-fucono-gamma-lactone, but not by D-galactose, D-galactono-gamma-lactone, D-glucose or D-glucono-gamma-lactone; the latter compounds are specific inhibitors of beta-D-galactosidase and beta-D-glucosidase respectively. Thus, this enzyme is the most strictly specific beta-D-fucosidase when compared with those previously reported.
 ...
PMID:[Studies on the beta-D-fucosidase from Aspergillus phoenicis]. 159 57

The relationship between muscarinic receptor activation of phosphoinositide hydrolysis and the sequestration of cell surface muscarinic receptors has been examined for both intact and digitonin-permeabilized human SK-N-SH neuroblastoma cells. Addition of the aminosteroid 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino] hexyl]-1H-pyrrole-2,5-dione (U-73122) to intact cells resulted in the inhibition of oxotremorine-M-stimulated inositol phosphate release and of Ca2+ signaling by greater than 75%. In contrast, when phospholipase C was directly activated by the addition of the calcium ionophore ionomycin, inclusion of U-73122 had little inhibitory effect. Addition of U-73122 to intact cells also inhibited the agonist-induced sequestration of cell surface muscarinic receptors and their subsequent down-regulation with an IC50 value (4.1 microM) similar to that observed for inhibition of inositol phosphate release (3.7 microM). In contrast, when oxotremorine-M-stimulated phosphoinositide hydrolysis was inhibited by depletion of extracellular Ca2+, no reduction in the extent of receptor sequestration was observed. When introduced into digitonin-permeabilized cells, U-73122 more markedly inhibited inositol phosphate release elicited by either oxotremorine-M or guanosine-5'-O-(3-thiotriphosphate) than that induced by added Ca2+. Addition of oxotremorine-M to permeabilized cells resulted in muscarinic receptor sequestration and down-regulation. Both the loss of muscarinic acetylcholine receptors and activation of phosphoinositide hydrolysis in permeabilized cells were inhibited by the inclusion of guanosine-5'-O-(2-thiodiphosphate). The results indicate that the agonist-induced sequestration of muscarinic acetylcholine receptor in SK-N-SH cells requires the involvement of a GTP-binding protein but not the production of phosphoinositide-derived second messenger molecules.
 ...
PMID:The aminosteroid U-73122 inhibits muscarinic receptor sequestration and phosphoinositide hydrolysis in SK-N-SH neuroblastoma cells. A role for Gp in receptor compartmentation. 166 Aug 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>