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)

Amphipathic compounds containing N-acetylneuraminic acid (sialic acid) [for example, D-N-acetylneuraminyl-(alpha 2-1)-2S,3R,4E-2-N-tetracosanoyl sphingenine, sialyl alkyl glycerol ethers, and sialyl cholesterols] induced neuritogenesis in a neuroblastoma cell line (Neuro2a). The sialic acid in the hydrophilic moiety of the compounds is specifically required for neuritogenesis. The requirement for molecular specificity of the hydrophobic moiety, however, is rather low. Regarding the hydrophobic moiety, no preference for cholesterol, alkyl glycerol ether, or ceramide residues was observed as to their neuritogenic activity. Sialyl compounds with alpha-ketosidic sialyl linkages were more active than the corresponding beta-anomers. These sialyl compounds induced the growth of only one neurite, but a long one, from the cell body. This type of neuritogenes is completely different from that induced by compounds capable of elevating the concentration of intracellular cyclic AMP, which induced the appearance of many neurites from a single cell body. Besides this morphological change, the active sialyl compounds also caused a change in the carbohydrate composition of the cell surface. Sialyl compound treatment drastically increased the concentration of peanut agglutinin binding sites.
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PMID:Synthetic sialyl compounds as well as natural gangliosides induce neuritogenesis in a mouse neuroblastoma cell line (Neuro2a). 282 94

The T3 concentration in brain predominantly reflects local production from T4 rather than T3 uptake from the circulating pool. We recently demonstrated that rat brain T3 content is increased by glucose feeding compared to chow feeding. One possible mechanism for this effect is an increase in brain T4 5'-deiodinase (5'-D) activity. Our recent preliminary studies of neuroblastoma (NB) cells demonstrate that renewal of RPMI-1640 medium stimulates T4 5'-D type II (NB T4 5'-D II) activity in these cells. The present studies were performed to determine the mechanism of this response. Studies were performed on NB cells supported in thyroid hormone-depleted (deficient) medium. This approach increased NB T4 5'-DII activity 4-fold compared to that in thyroid hormone-replete medium. Medium renewal further stimulated enzyme activity (7- to 9-fold; maximum at 6 h) in each group. The difference between the hypothyroid group and control was sustained over a 24-h period. Subsequent studies demonstrated that glucose (11 mM) was the specific medium ingredient mediating the medium renewal response. A progressive increase in NB T4 5'-DII activity was noted over 8 h during RPMI-1640 salt plus glucose (11 mM) incubation. This was equivalent to the effect of complete medium containing glucose (11 mM). Coincubation with insulin (10(-7)-10(-9) M) did not modify the enzyme response to glucose. In addition, fructose (10 mM) had a similar effect on enzyme activity. Glycerol and essential and nonessential amino acids also modestly increased NB T4 5'-DII activity compared to that in the control group (P less than 0.01). Actinomycin-D (1 microM), cycloheximide (100 microM), and puromycin (100 microM) significantly (P less than 0.001) decreased the glucose effect on T4 5'-DII by 5-, 9-, and 17-fold, respectively, after 6 h of incubation. In addition, puromycin (10-200 microM) inhibited both NB T4 5'-DII activity and [3H]amino acid incorporation during incubation in glucose. There was a significant correlation between these parameters (r = 0.8; P less than 0.001). The enzyme activity decay curves in the glucose-activated and control groups subsequent to puromycin (100 microM) addition at 8 h were parallel. The fractional turnover rate was 13%/h in the controls and 11%/h in the glucose groups. The calculated enzyme production rate was significantly higher (P less than 0.005) in the glucose group compared to that in the control group (17.4 vs. 6.8 fmol/mg protein.h).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Carbohydrate reactivation of thyroxine 5'-deiodinase (type II) in cultured mouse neuroblastoma cells is dependent upon new protein synthesis. 291 91

A glycerol-containing analog of ganglioside, with sialic acid attached to a diglyceride-like structure possessing two ether-linked alkyl chains, was prepared synthetically and applied exogenously to three culture systems; neuro-2A neuroblastoma cells, PC12 cells and dorsal root ganglia. This resulted in pronounced stimulation of neurite outgrowth in all three, demonstrating that sialo-lipids(s) lacking ceramide and possessing sialic acid as the sole carbohydrate are able to promote neuritogenesis in approximately the same manner as naturally occurring gangliosides.
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PMID:Stimulation of neurite outgrowth in vitro by a glycero-ganglioside. 318 72

Inositol phospholipid turnover is part of a signal transduction mechanism which mobilize intracellular calcium and activate a calcium- and phospholipid-dependent protein kinase, protein kinase C. Phosphatidylinositol turnover has recently been implicated in the regulation of cell proliferation and transformation. Its role in differentiation has now been investigated using LAN-1 cells, a human neuroblastoma cell line which can be induced to differentiate along the neuronal pathway by RA. Treatment of LAN-1 cells with RA was followed by a rapid decrease of inositol phospholipid metabolism, as determined by isotopic methodology employing myo-[1,2-3H] inositol or [1(3)-3H] glycerol. Analysis of labelled phosphatidylinositol metabolites from prelabelled cells indicated a rapid decrease of inositol (1,4,5)trisphosphate and (1,2)diacylglycerol within 1 min. of induction of LAN-1 cell differentiation. These findings suggest that inositol phospholipid-derived metabolites (i.e. diacylglycerol and inositol trisphosphate) may be part of the mechanism by which certain RA signals are transduced, playing a key role in control of neuroblastoma cell differentiation.
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PMID:[A rapid decrease in the phosphatidylinositol cycle during neuroblastoma cell differentiation induced by retinoic acid]. 327 73

Neuroblastoma cells rapidly incorporate exogenous fatty acids into cellular triacylglycerol and relationships between triacylglycerol and phospholipid biosynthesis have been indicated by the relative time course of labeling of these lipids. To evaluate this further, neuroblastoma cells were labeled using potential precursors of phospholipid including radiolabeled triacyglycerol, glycerol, glucose, and fatty acid. With [2-3H]glycerol or a mixture of [2-3H]glycerol trioleate and glycerol tri[1-14C]oleate, phospholipids were labeled at very low levels (less than 0.1 and less than 0.5%, respectively). With [6-3H]glucose, labeling of lipids (0.5-3.5%) was greatest in medium containing 19 mM fructose, whereas labeling with [1-14C]18:2(n-6) was similar in media containing either 19 mM fructose or 25 mM glucose. Labeling of the glycerol moiety of triacylglycerol with [6-3H]glucose increased with 40-200 microM 18:2(n-6) present and occurred predominantly in 2 h. Some [6-3H]glucose label was in fatty acyl chains (chiefly 16:0) of triacylglycerol by 16 h, but was unaffected by exogenous 18:2(n-6). Triacylglycerol was the only lipid to increase in mass (threefold with 200 microM 18:2(n-6)). During the chase of cells pulsed with [6-3H]glucose, label in triacylglycerol declined within 0.5 h, whereas in phospholipid it increased transiently up to 2 h and then declined. Changes were inversely proportional to 18:2(n-6) levels in the chase medium and labeled acyl chains moved in parallel with the glycerol moiety. Thus, a major portion of acyl chain transfer from triacylglycerol was accompanied by glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Triacylglycerol as a precursor in phospholipid biosynthesis in cultured neuroblastoma cells: studies with labeled glucose, fatty acid, and triacylglycerol. 407 30

External application of bradykinin to neuroblastoma X glioma hybrid NG108-15 cells produced a sustained depolarization preceded by a transient hyperpolarization. Bradykinin also increased the frequency of miniature end-plate potentials recorded from cultured striated muscle cells which had been innervated by NG108-15 cells. Parallelism between facilitative phases of miniature end-plate potentials and depolarization indicates that bradykinin caused an enhanced synaptic transmission from NG108-15 cells due to depolarization. Effects of bradykinin on phospholipid metabolism in the hybrid cells were then examined to shed light upon the mechanism by which bradykinin-receptor interaction leads to facilitation of synaptic transmission. Bradykinin induced specific incorporation of 32Pi into phosphatidic acid and phosphatidylinositol without affecting [3H]glycerol incorporation into these phospholipids by 10 min after its addition. The addition of bradykinin to hybrid cells prelabeled with 32Pi caused a transient decrease (maximal effect seen at 10-30 s) in the radioactivity from phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2) which was followed by the accumulation of radioactivity in phosphatidic acid and phosphatidylinositol. A Ca2+ ionophore, A23187, failed to induce the initial degradation of PI-4,5-P2. The data show that the magnitudes of bradykinin-induced PI-4,5-P2 degradation and membrane potential changes in NG108-15 cells are both dependent on the concentration of bradykinin and that the degradation of PI-4,5-P2 precedes the electrophysiological responses. Taken together with the finding that bradykinin induced a transient increase in Ca2+ influx (at 10-20 s), it appears that a rapid and transient degradation of PI-4,5-P2 might be related to the initiation of the NG108-15 cell activities through mobilization of extracellular Ca2+ into the cells.
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PMID:Bradykinin-induced rapid breakdown of phosphatidylinositol 4,5-bisphosphate in neuroblastoma X glioma hybrid NG108-15 cells. 608 87

We investigated the effects of different protein kinase C (PKC) activators on Na+ currents using the conventional whole-cell and the inside-out macropatch voltage-clamp techniques in mouse neuroblastoma cells (N1E-115). Two different categories of PKC activators were investigated: the cis-unsaturated fatty acids (CUFAs): oleic (cis-9-octadecenoic), linoleic (cis-9-12-octadecadienoic), and linolenic acid (cis-9-12-15-octadecatrienoic), and, the diacylglycerol (DAG) derivative 1-2-dioctanoyl-sn-glycerol (DOG). These substances caused the following alterations on Na+ currents: (i) Na+ currents were attenuated as a function of voltage. While DOG attenuated both inward and outward Na+ currents in a monotonic and continuous voltage-dependent manner, CUFAs preferentially attenuated inward currents; (ii) the steady-state activation curve of Na+ currents shifted to more depolarized voltages; (iii) opposite to the activation curve, the steady-state inactivation curve of Na+ channels (h curve) shifted to more hyperpolarized voltages; (iv) the time course of inactivation development was accelerated by PKC activators, while the recovery from inactivation was not affected; (v) substances that inhibit different metabolic pathways (PKC activation, cyclooxygenase, lipooxygenase, and P-450 pathways) did not prevent the effects of PKC activators on Na+ currents. One fully saturated fatty acid (octadecanoic acid), a trans-unsaturated fatty acid (trans-9-octadecenoic), and different phorbol esters did not affect Na+ currents; (vi) effects of different PKC activators on Na+ currents were completely reversible. These observations suggest that PKC activators might interact with Na+ channels directly. These direct effects must be taken into consideration in evaluating the overall effect of PKC activation on Na+ channels. Moreover, it is likely that this direct interaction could account, at least in part, for the diversity of effects of PKC activators on Na+ channels.
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PMID:Direct modulation of Na+ currents by protein kinase C activators in mouse neuroblastoma cells. 759 42

Protein phosphorylation and subsequent dephosphorylation was studied in digitonin-permeabilized neuroblastoma SH-SY5Y cells by measuring the incorporation of [32P]phosphate into myelin basic protein (MBP). 1,2-Dioctanoyl-sn-glycerol (DOG) and calcium synergistically induced phosphorylation of MBP, which was inhibited by the protein kinase C (PKC) pseudosubstrate peptide (PKC19-36). The phosphorylation increased for 10 min when a net dephosphorylation started to appear. The dephosphorylation was inhibited by okadaic acid. Regardless of calcium concentration, the presence of DOG was necessary for significant effects of okadaic acid on MBP phosphorylation. H7 and staurosporine dose-dependently inhibited the phosphorylation of MBP, induced by DOG and calcium in the presence of okadaic acid. Different PKC pseudosubstrate peptides were applied and all showed an inhibitory effect on the phosphorylation of MBP under these conditions. These results demonstrate the presence, in SH-SY5Y cells, of a protein phosphatase, possibly protein phosphatase 2A, with a high basal activity that counteracts PKC-induced phosphorylation.
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PMID:An okadaic acid-sensitive protein phosphatase counteracts protein kinase C-induced phosphorylation in SH-SY5Y cells. 768 46

The effects of externally applied different protein kinase C (PKC) activators on Na+ currents in mouse neuroblastoma cells were studied using the perforated-patch (nystatin-based) whole cell voltage clamp technique. Two diacylglycerol-like compounds, OAG (1-oleoyl-2-acetyl-sn-glycerol), and DOG (1-2-dioctanoyl-rac-glycerol) attenuated Na+ currents without affecting the time course of activation or inactivation. The reduction in Na+ current amplitude caused by OAG or DOG was dependent on membrane potential, being more intense at positive voltages. The steady-state activation curve was also unaffected by these substances. However, both OAG and DOG shifted the steady-state inactivation curve of Na+ currents to more hyperpolarized voltages. Surprisingly, phorbol esters did not affect Na+ currents. Cis-unsaturated fatty acids (linoleic, linolenic, and arachidonic) attenuated Na+ currents without modifying the steady-state activation. As with DOG and OAG, cis-unsaturated fatty acids also shifted the steady-state inactivation curve to more negative voltages. Interestingly, inward currents were more effectively attenuated by cis-fatty acids than outward currents. Oleic acid, also a cis-unsaturated fatty acid, enhanced Na+ currents. This enhancement was not accompanied by changes in kinetic or steady-state properties of currents. Enhancement of Na+ currents caused by oleate was voltage dependent, being stronger at negative voltages. The inhibitory or stimulatory effects caused by all PKC activators on Na+ currents were completely prevented by pretreating cells with PKC inhibitors (calphostin C, H7, staurosporine or polymyxin B). By themselves, PKC inhibitors did not affect membrane currents. Trans-unsaturated or saturated fatty acids, which do not activate PKC's, did not modify Na+ currents. Taken together, the experimental results suggest that PKC activation modulates the behavior of Na+ channels by at least three distinct mechanisms. Because qualitatively different results were obtained with different PKC activators, it is not clear how Na+ currents would respond to activation of PKC under physiological conditions.
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PMID:Multiple effects of protein kinase C activators on Na+ currents in mouse neuroblastoma cells. 793 44

A sucrose-magnesium chloride-glycerol storage solution (sucrose-magnesium chloride) can preserve antigenicity of cytologic preparations for prolonged periods of time. This storage method was evaluated relative to our immunocytologic technology with the specific aim of exploring its use as a quality control measure. Neuroblastoma and leukemia cell lines, patient bone marrow, and blood specimens were serially tested during a 15-week period to evaluate preservation of immunoreactivity and cell morphological features. Slides that had been air dried and stored at 4 degrees C were compared with those that had been fixed with methanol and paraformaldehyde and stored in sucrose-magnesium chloride at -20 degrees C. The sucrose-magnesium chloride method proved to be superior, and antigen-antibody binding and cell morphology were preserved even after 15 weeks of storage. This method, now in use as a quality control measure in our laboratory, constitutes a practical assurance program for immunocytologic analysis.
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PMID:Quality control of immunocytologic testing. Prolonged preservation of cell surface antigen reactivity with magnesium chloride-sucrose solution. 823 43


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