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 human neuroblastoma cell line SK-N-BE can be induced to differentiate by retinoic acid (RA) or by alpha-difluoromethylornithine (DFMO). The former inducer produces neurite outgrowth, 60% reduction of growth rate, overexpression of neural antigens, and enhanced gamma-aminobutyric acid (GABA) and acetylcholinesterase levels. In contrast, DFMO causes cell body elongation, complete growth inhibition, and higher binding of antibodies directed against neuroectodermal antigens. Polyamine metabolism is also differently affected by the two agents. In particular a large spermine catabolism is induced by RA, while DFMO treatment leads to a small increase in the level of this compound. The neural differentiation induced by RA is accompanied by a marked increase in transglutaminase activity and its induction is paralleled by a transient increase of putrescine and spermidine. The putrescine and spermidine depletion determined by DFMO is accompanied instead by a large inhibition of transglutaminase activity. The inhibiting effect of DFMO treatment on transglutaminase is reversed by the addition of 1 mM putrescine to the culture medium. In the presence of both RA and DFMO a mixed morphological and biochemical pattern is observed. The possibility that the expression of transglutaminase associated to cellular differentiation may be modulated by the level of its substrates is also discussed.
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PMID:Correlation between transglutaminase activity and polyamine levels in human neuroblastoma cells. Effect of retinoic acid and alpha-difluoromethylornithine. 290 30

Choline acetyltransferase (Acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6, abbreviated ChAT), the biosynthetic enzyme for acetylcholine and acetylcholinesterase (EC 3.1.1.7, abbreviated AChE) are expressed in a human cholinergic neuroblastoma cell line, MC-IXC. We have shown that ChAT activity can be regulated in culture by retinoic acid, an active metabolite of vitamin A, and by sodium butyrate, an organic fatty acid. Optimal concentrations of these agents produce 4.3-fold and 1.6-fold increases in ChAT activity, respectively. The effects of retinoic acid are statistically significant after 24 h, whereas for sodium butyrate significant differences are seen only after 48 h. Since retinoic acid stimulation of ChAT activity was reversed only by trypsin treatment and not by removal of retinoic acid from the medium, this suggests that this agent may be acting at the level of the cell surface. Other differentiating conditions, such as culture in serum-free medium or addition of 1-2% dimethylsulfoxide did not increase ChAT activity. Acetylcholinesterase activity was shown to increase only in the presence of sodium butyrate, suggesting that retinoic acid and sodium butyrate may be acting via different pathways. Retinoic acid and sodium butyrate both seem to be permissive rather than instructive in regulating ChAT activity in that they are unable to induce ChAT expression de novo in cell lines which do not already express ChAT activity.
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PMID:Stimulation of choline acetyltransferase activity by retinoic acid and sodium butyrate in a cultured human neuroblastoma. 292 23

The mouse neuroblastoma cell line NB2A produces cellular and secreted acetylcholinesterase (AChE). After incubation of the cells for 4 days the ratio between AChE secreted into the medium and AChE in the cells was 1:1. The cell-associated enzyme could be subdivided into soluble AChE (25%) and detergent-soluble AChE (75%). Both extracts contained predominantly monomeric AChE (4.6S) and minor amounts of tetrameric AChE (10.6S), whereas the secreted AChE in the culture supernatant contained only the tetrameric form. All forms were partially purified by affinity chromatography. It could be demonstrated that the secretory and the intracellular soluble tetramers were hydrophilic, whereas the detergent-soluble tetramer was an amphiphilic protein. On the other hand the soluble and the detergent-soluble monomeric forms were amphiphilic and their activity depended on the presence of detergent. By digestion with proteinase K amphiphilic monomeric and tetrameric AChE could be converted to a hydrophilic form that no longer required detergent for catalytic activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [3H]diisopropylfluorophosphate-labelled AChE gave one band at 64 kilodaltons (kD) under reducing conditions and two additional bands at 120 kD and 140 kD under nonreducing conditions.
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PMID:Acetylcholinesterase in mouse neuroblastoma NB2A cells: analysis of production, secretion, and molecular forms. 292 96

Morphological characteristics of undifferentiated and differentiated human neuroblastoma cells were studied. Monolayer cultures of a human neuroblastoma, IMR-32 clone, were grown in Eagle's minimum essential medium with fetal calf serum in tissue culture dishes with polystyrene film liners. After 48 h, cultures were treated with either mitomycin C and 5-bromodeoxyuridine or prostaglandin E1 (PGE1) and dibutyryl adenosine 3',5'-cyclophosphate (cAMP). A third dish was untreated to study as an undifferentiated control. Three days later, all cultures were processed for acetylcholinesterase staining, scanning and transmission electron microscopy and high performance liquid chromatography. Treatment with mitomycin/5-bromodeoxyuridine and PGE1/cAMP inhibited growth as seen by the growth curves and caused morphological differentiation as seen by the extension of long neurites. The treated cells showed increased acetylcholinesterase staining compared to the controls. With the scanning electron microscope, the differentiated cells showed long neurites, processes with beaded varicosities and growth cones. By transmission electron microscopy, these cells contained a large number of neurosecretory granules in their cytoplasm and neurites. Specialized cell contacts were also observed between the treated cells. This is the first study demonstrating that both the treated and control cells of IMR-32 clone contain large quantities of serotonin and comparatively small amounts of norepinephrine and dopamine.
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PMID:Differentiation characteristics of human neuroblastoma cells in the presence of growth modulators and antimitotic drugs. 298 88

The phorbol ester tumor promoter phorbol-12-myristate-13-acetate (PMA) was found to have differential inhibitory effects on the expression of morphological and biochemical differentiation of N-18 mouse neuroblastoma cells. PMA completely inhibited neurite extension and associated growth characteristics and partially inhibited the increased expression of R1 cAMP-binding protein; PMA had no effect on the induction of acetylcholinesterase activity in cells prompted to differentiate either by treatment with 1 mM dibutyryl cAMP or by serum deprivation. 4-alpha-Phorbol-12, 13-didecanoate, an inactive analogue of phorbol ester tumor promoter, was without effect. The implications of these findings concerning the mechanism of action of phorbol ester tumor promoters in the control of cell differentiation are discussed.
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PMID:Differential effects of the tumor promoter phorbol-12-myristate-13-acetate on the morphological and biochemical differentiation of N-18 mouse neuroblastoma cells. 299 62

We have characterized and quantitated the level of cAMP-dependent protein kinase in the NS-20, N1E-115, N-18 and N1A-103 mouse neuroblastoma clonal cell lines, and we have correlated the occurrence of functional cAMP-dependent protein kinase with the dibutyryl cAMP-induced differentiated functions in these cells. Our results demonstrate the presence of functional cAMP-dependent protein kinase in extracts of all four cell lines examined, including the 'neurite minus' N1A-103 cell line. Dibutyryl cAMP induced neurite outgrowth and acetylcholinesterase activity in the NS-20, N1E-115 and N-18 neuroblastoma cell lines, but not in the N1A-103 cell line. However, dibutyryl cAMP caused a 2-3-fold increase in the R1 regulatory subunit protein and cAMP-phosphodiesterase activity in the 'neurite minus' N1A-103 cells in a manner similar to that of the other three 'neurite positive' cell lines. These results suggest that the biochemical lesion(s) subserving the neurite-minus phenotype of the N1A-103 cells may be distal to the activation of cAMP-dependent protein kinase and is in a biochemical pathway distinct from the induction of R1 regulatory subunit protein and cAMP-phosphodiesterase activity.
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PMID:Identification of functional cAMP-dependent protein kinase in a 'neurite minus' mouse neuroblastoma cell line. 303 79

On the basis that inhibition of cell proliferation may play a role in the differentiation process, we have studied the effect of the antineoplastic drug epirubicin, an antibiotic of the anthracycline group, on human neuroblastoma cell lines SK-N-MC, SK-N-SH, SJ-N-KP, TS12 and AF8. Epirubicin induced morphological and biochemical differentiation in these cultured cell lines; treatment with it stimulated the outgrowth of neurites and increased acetylcholinesterase activity.
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PMID:Epirubicin-induced differentiation of human neuroblastoma cells in vitro. 347 74

Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used as precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here we used a population of purely cholinergic cells (human neuroblastoma, LA-N-2), incubated in the presence of [methyl-3H]methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. PtdCho, purified by thin-layer chromatography, contained 90% of the label incorporated into lipids, demonstrating that LA-N-2 cells contained phosphatidylethanolamine N-methyltransferase. Three peaks of radioactive material that cochromatographed with authentic Ac-Cho, choline, and phosphocholine were observed when the water-soluble metabolites of the [3H]PtdCho were purified by high-performance liquid chromatography. Their identities were ascertained by subjecting them to enzymatic modifications with acetylcholinesterase, choline oxidase, and alkaline phosphatase, respectively. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine.
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PMID:Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line. 347 63

The cellular localization of acetylcholinesterase (AChE) was investigated at the electron microscope (E.M.) in a neuroblastoma and neuroblastoma x glioma hybrid line, which differ for their ability to establish synaptic contacts. Only cells of the latter line show association of AChE to the plasmamembrane, while in the former the activity is mainly intracellular. Sucrose sedimentation analysis of AChE molecular forms has shown no significant differences in the distribution of the two forms, G2 and G4, between the two cell lines. On the contrary a marked difference is observed in the ability of the cell to release the enzyme in the culture medium. In fact the cells lacking AChE on their surface release in the medium a much higher proportion of their enzyme, than the cells showing AChE association to their plamamembrane. The possible role of two alternative fates for AChE, secretion or membrane insertion, in determining the observed differences of enzyme localization is discussed.
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PMID:Acetylcholinesterase in neuroblastoma and neuroblastoma x glioma hybrid cells: cellular localization and molecular forms. 350 13

Preclinical pharmacologic studies of caracemide [N-acetyl-N-(methylcarbamoyloxy)-N'-methylurea; CAR] have demonstrated a marked instability of this compound in the presence of either phosphate buffer (pH 7.4) or human plasma. Using [1-14C-acetyl]CAR and [3H-methylcarbamoyloxy]CAR, three CAR degradation products were identified: product A, N-(methylcarbamoyloxy)acetamide; product B: N-(methylcarbamoyloxy)-N'-methylurea; and product C: N-hydroxy-N'-methylurea. CAR degradation in human plasma was demonstrated by high-performance liquid chromatography (HPLC) to occur in a time- and temperature-dependent manner. A 30-min incubation (37 degrees) of CAR (10(-4) M) with human plasma resulted in degradation of more than 55% of parent compound; at 1 hr, more than 75% of original CAR was degraded. Incubation of [1-14C-acetyl]CAR with rat brain homogenate resulted in the formation of 14CO2. This reaction was partially inhibited by coincubation with physostigmine (10(-3) M). CAR inhibited acetylcholinesterase activity in neuroblastoma cells with an IC50 of 14 microM. In mechanism of action studies, CAR was found to inhibit ribonucleotide reductase activity but only at nine times the IC50 of hydroxyurea. In contrast to hydroxyurea, CAR was found to be non-cell-cycle phase-specific and non-cross-resistant with two CHO cell lines resistant to hydroxyurea. These data demonstrate the instability of CAR; moreover, they suggest that its mechanism of cytotoxicity is distinctly different from that of hydroxyurea and that the neurotoxicity associated with CAR administration may be caused in part by inhibition of acetylcholinesterase activity.
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PMID:Biochemical pharmacology of N-acetyl-N-(methylcarbamoyloxy)-N'-methylurea (caracemide; NSC-253272). 352 74


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