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)

Cholera toxin (CT), covalently attached to horseradish peroxidase (HRP), is a specific cytochemical marker for GM1 ganglioside (GM1) and retains the ability of the native toxin to raise levels of cyclic AMP in avian erythrocytes. Using a cytochemical stain for HRP, we found that 9% of control cultured murine neuroblastoma cells bound cholera toxin-horseradish peroxidase conjugates (CT-HRP) on their surfaces after incubations for 1 h at 4 degrees C. Exogenous GM1, the natural receptor of CT, becomes associated in the culture medium with the plasma membranes of these cells so that 96% of cells are stained. Cells preincubated with GM1 at 4 degrees C were exposed to CT-HRP for 1 h at 4 degrees C. After washing, cells were incubated at 37 degrees C for 30 min-24 h. Endocytosis of CT-HRP occurred within 30 min and CT-HRP remained, throughout the 24-h period, in tubules, vesicles, and cisternae often found near the Golgi apparatus; this aggregate of peroxidase-positive elements probably corresponds to Golgi apparatus-endoplasmic reticulum-lysosomes (GERL) of neurons. In metaphase cells, CT-HRP was observed in aggregates of vesicles and tubules clustered near the centriole. Conjugates of HRP with subunit B, the GM1 binding component of CT, were internalized by cells pretreated with GM1 as was CT-HRP. The 9% of neuroblastoma cells binding CT-HRP in the absence of exogenous GM1 internalized the ligand in a manner indistinguishable from that of the treated cells. These findings indicate that, in neuroblastoma cells, a system of vesicles, tubules, and cisternae, analogous to GERL of neurons, is the primary recipient of adsorptive endocytosis of CT bound to endogenous or exogenously introduced GM1.
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PMID:Endocytosis of cholera toxin in GERL-like structures of murine neuroblastoma cells pretreated with GM1 ganglioside. Cholera toxin internalization into Neuroblastoma GERL. 45 74

Ultrastructural features of neoplastic cells can provide clues for correct diagnosis when light microscopy fails. Secretory granules are characteristic in the following tumors: mucin granules in poorly differentiated adenocarcinomas, zymogen granules in acinic cell carcinomas, lysosomal granules in prostatic carcinomas, melanin granules in malignant melanoma, carcinoid, islet cell tumors, pheochromocytoma, and neuroblastoma granules in the corresponding neoplasms. Among cytoplasmic organelles, rough surfaced endoplasmic reticulum characterizes adrenocortical, ovarian, and hepatocellular carcinomas and plasmacytomas. Tonofibrils are characteristic of squamous cell carcinomas. Glycogen deposits distinguish Ewing's sarcoma from lymphoreticular neoplasms. Intercellular relationships and membrane specialization are important features in the differential diagnosis of various undifferentiated tumors. The frequent resolution of difficult diagnostic problems by electron microscopy outweighs the disadvantages of this technique, such as the expense and time required.
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PMID:The usefulness of electron microscopy in the diagnosis of human tumors. 115 Feb 21

Two cases of Ewing's sarcoma and two neuroblastoma, rosette forming and round cell type, were studied electron microscopically and their fine structures were compared. The neoplastic cells of Ewing's sarcoma were characterized by aggregated glycogen particles in the cytoplasm. They had pseudopod-like cytoplasmic processes having tight junctions, which never contained microtubules or mitochondria. Ewing's sarcoma cells exhibited several stages of cell maturation and some mature cells possessed a large amount of smooth and rough endoplasmic reticulum, large Golgi complexes and numerous phagosomes containing glycogen particles as well as cytoplasmic organelles. The neoplastic cells of neuroblastoma, rosette forming type, were characterized by synaptic junctions and numerous cytoplasmic processes with production of neurites containing microtubules, neurofibrils, mitochondria and a few catecholamine granules. A few cytoplasmic processes containing mitochondria were observed even in the round cell type.
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PMID:Fine structural comparison of Ewing's sarcoma with neuroblastoma. 115 91

The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.
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PMID:Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay. 127 91

Endothelin-1 (ET-1) produced a dose-dependent increase of intracellular Ca++ concentrations [Ca++]i characterized by an early peak phase and a delayed plateau in LAN-1 human neuroblastoma cells. The ET-1 receptor showed a rapid desensitization since a second pulse application of ET-1 did not elicit a further [Ca++]i increase. Furthermore thapsigargin, an endoplasmic reticulum Ca(++)-ATPase inhibitor, completely abolished the ET-1 induced intracellular Ca++ elevation.
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PMID:LAN-1 human neuroblastoma cells are provided of endothelin-1 receptors linked to [Ca++]i elevation. 132 9

Scrapie prions are composed largely, if not entirely, of the scrapie prion protein (PrPSc) that is encoded by a chromosomal gene. Scrapie-infected mouse neuroblastoma (ScN2a) and hamster brain (ScHaB) cells synthesize PrPSc from the normal PrP isoform (PrPC) or a precursor through a posttranslational process. In pulse-chase radiolabeling experiments, we found that presence of brefeldin A (BFA) during both the pulse and the chase periods prevented the synthesis of PrPSc. Removal of BFA after the chase permitted synthesis of PrPSc to resume. BFA also blocked the export of nascent PrPC to the cell surface but did not alter the distribution of intracellular deposits of PrPSc. Under the same conditions, BFA caused the redistribution of the Golgi marker MG160 into the endoplasmic reticulum (ER). Using monensin as an inhibitor of mid-Golgi glycosylation, we determined that PrP traverses the mid-Golgi stack before acquiring protease resistance. About 1 h after the formation of PrPSc, its N-terminus was removed by a proteolytic process that was inhibited by ammonium chloride, chloroquine, and monensin, arguing that this is a lysosomal event. These results suggest that the ER is not competent for the synthesis of PrPSc and that the synthesis of PrPSc occurs during the transit of PrP between the mid-Golgi stack and lysosomes. Presumably, the endocytic pathway features in the synthesis of PrPSc.
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PMID:Synthesis and trafficking of prion proteins in cultured cells. 135 22

Continuous superfusion of rat glioma cells with medium containing bradykinin (from 0.2 nM) induced a transient hyperpolarization followed by regular hyperpolarizing oscillations of the membrane potential. Similar repetitive hyperpolarizing oscillations were caused by extracellularly applied bradykinin or muscarine or by intracellularly injected GTP-gamma-S. The frequency of the oscillations was 1 per minute at bradykinin concentrations ranging from 0.2 nM to 2 microM, but the amplitude and duration increased with rising peptide concentration. The muscarine-induced oscillations were blocked by atropine. In the presence of extracellular Ca2+, the substances thapsigargin, 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), and ionomycin reversibly suppressed the bradykinin-induced oscillations. Thapsigargin and tBuBHA, which are known to block the Ca2+ ATPase of endoplasmic reticulum, caused a transient rise in cytosolic Ca2+ activity, monitored with Fura-2, in suspensions of rat glioma cells or of mouse neuroblastoma-rat glioma hybrid cells. After a transient Ca2+ rise caused by thapsigargin, tBuBHQ, or ionomycin, the Ca2+ response to bradykinin which is known to be due to release of Ca2+ from internal stores was suppressed. This indicates that thapsigargin and tBuBHQ deplete internal Ca2+ stores as already seen previously for ionomycin. Thus, the inhibition of the membrane potential oscillations by thapsigargin, tBuBHQ, and ionomycin indicates that the oscillations are associated with activation of InsP3-sensitive Ca2+ stores. In some cells composite oscillation patterns which consisted of two independent oscillations with different amplitudes that overlapped additively were seen. We discuss that this pattern and the concentration dependency of the oscillations could be due to "quantal" Ca2+ release from stores with different inositol 1,4,5-triphosphate sensitivities. Subsidence of the oscillations after omission of extracellular Ca2+ seems to be due to a lack of replenishment of the intracellular stores with Ca2+, which comes from the extracellular compartment.
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PMID:Bradykinin and muscarine induce Ca(2+)-dependent oscillations of membrane potential in rat glioma cells indicating a rhythmic Ca2+ release from internal stores: thapsigargin and 2,5-di(tert-butyl)-1, 4-benzohydroquinone deplete InsP3-sensitive Ca2+ stores in glioma and in neuroblastoma-glioma hybrid cells. 139 96

Infectious scrapie prions are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrP) designated PrPSc. In scrapie-infected mouse neuroblastoma (ScN2a) and hamster brain (ScHaB) cells, PrPSc accumulates primarily within the cell cytoplasm, whereas cellular PrP (PrPC) is anchored to the external surface of the plasma membrane by a glycoinositol phospholipid moiety. To determine the subcellular localization of PrPSc, scrapie-infected cells were grown to approximately 75% confluency, fixed briefly, and then incubated with guanidine thiocyanate before antibody staining and examination by electron microscopy. PrPSc immunoreactivity was enhanced by denaturation with guanidine isothiocyanate which also permeabilized cells (Taraboulos et al., J Cell Biol 110:2117, 1990). As judged both by deposition of immunoperoxidase reaction product (diaminobenzidine) and by presence of immunogold particles, PrPSc was identified in discrete vesicular foci and some large bodies in the cytoplasm of scrapie-infected cells. Some vesicles with PrPSc staining also contained myelin figures resembling those found in autophagic vacuoles forming secondary lysosomes. The presence of PrPSc in secondary lysosomes is inferred from colocalization of guanidine isothiocyanate enhanced PrP immunoreactivity and acid phosphatase. Neither the diaminobenzidine reaction product nor immunogold particles were observed in association with the nucleus, endoplasmic reticulum, or Golgi stacks. Exposure of scrapie-infected cells to the brefeldin A dispersed the Golgi apparatus but did not alter the morphologic distribution of PrPSc, indicating that no detectable PrPSc was associated with Golgi stacks. It remains to be established whether secondary lysosomes are involved in the post-translational formation of PrPSc.
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PMID:Ultrastructural localization of scrapie prion proteins in cytoplasmic vesicles of infected cultured cells. 168 1

Accumulation of paired helical filaments (PHF) in neurofibrillary tangles is a key neuropathological hallmark in Alzheimer's disease (AD). To date, PHF have been found primarily in humans. Cultured murine cholinergic neuroblastoma (S20Y) cells, following exposure to a serum-free medium or a differentiation medium, developed immunoreactivity to anti-PHF antibodies, and to the Alz-50 by immunocytochemical and immunoblot analyses. Electron microscopic examination revealed abundant fascicles of 10-nm filaments coursing tortuously amongst organelles, such as mitochondria, endoplasmic reticulum and dense-core vesicles, in perikarya and in neuritic extensions. However, subcellular structures identical or similar to PHF could not be found in these non-human cells. This convenient cell culture model may prove to be useful for studying certain aspects of the mechanisms underlying the abnormal cytoskeletal alterations which are characteristic of AD and related neurodegenerative disorders.
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PMID:Induction of epitopes associated with neurofibrillary tangles in clonal mouse neuroblastoma (S20Y) cells. 170 74

Two types of binding sites have previously been described for neuropeptide Y (NPY), called Y1 and Y2 receptors. The intracellular events following Y1 receptor activation was studied in the human neuroblastoma cell line SK-N-MC. Both NPY and the specific Y1 receptor ligand, [Leu31,Pro34]-NPY, caused a rapid and transient increase in the concentration of free calcium in the cytoplasm as measured by the fluorescent probe, Fura-2. The effect of both peptides was independent of extracellular calcium as addition of EGTA or manganese neither changed the size nor the shape of the calcium response. The calcium response to NPY was abolished by pretreatment with thapsigargin, which can selectively deplete a calcium store in the endoplasmic reticulum. Y1 receptor stimulation, by both NPY and [Leu31,Pro34]NPY, also inhibited the forskolin-stimulated cAMP production with an EC50 of 3.5 nM. There was a close relation between the receptor binding and the cellular effects as half-maximal displacement of [125I-Tyr36]monoiodoNPY from the receptor was obtained with 2.1 nM NPY. The Y2-specific ligand NPY(16-36)peptide had no effect on either intracellular calcium or cAMP levels in the SK-N-MC cells. It is concluded that Y1 receptor stimulation is associated with both mobilization of intracellular calcium and inhibition of adenylate cyclase activity.
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PMID:Y1 receptors for neuropeptide Y are coupled to mobilization of intracellular calcium and inhibition of adenylate cyclase. 215 77


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