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)

myo-Inositol uptake was investigated in a murine neuroblastoma clone (N1E-115) to determine the effect of altered Na+,K+-ATPase activity. The Na+ ionophore monensin, and veratridine, an alkaloid affecting voltage-dependent Na+ entry, increased acute 22Na+ uptake and 22Na+ efflux from pre-loaded cells, concomitant with enhanced myo-inositol uptake. This effect was also seen following insulin. Insulin-stimulated myo-inositol uptake was inhibited by amiloride, ouabain and pyrithiamine. Amiloride inhibition suggests that activation of Na+/H+ exchange preceding Na+,K+-ATPase activation is involved in insulin stimulation of myo-inositol uptake. Pyrithiamine inhibition is an indication of prior activation of the Na+,K+-ATPase alpha + catalytic subunit by insulin. The results provide evidence that insulin contributes to the maintenance of Na+,K+-ATPase in neuronal tissue.
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PMID:Acute changes in myo-inositol uptake and 22Na+ flux in murine neuroblastoma cells (N1E-115) following insulin. 330 13

Typical insulin receptors are present on neuroblastoma cell lines. High affinity binding for insulin was present in membrane preparations from NG108 (a hybrid mouse neuroblastoma-rat glioma) as well as in membranes from SK-N-MC and SK-N-SH, two human neuroblastoma cell lines. Specific [125I]insulin binding was 24.4% for NG108, 16.9% for SK-N-MC and 5.2% for SK-N-SH at membrane protein concentrations of 0.4 mg/ml. IC50 for [125I]insulin binding was 3.4 nM in NG108 membrane preparations and 0.9 nM for SK-N-SH and 1.8 nM in SK-N-MC membranes. Apparent mol. wt. for the alpha subunits (identified by specific immunoprecipitation using the anti-insulin receptor antiserum B10) on SDS PAGE was 134 kDa for NG108; 124 kDa for SK-N-MC and 120 kDa for SK-N-SH. Neuraminidase digestion increased the mobility of the alpha subunit from both NG108 and SK-N-MC receptors to 120 kDa, whereas that from SK-N-SH were unaffected. Endoglycosidase H and endoglycosidase F digestions increased the mobility of the alpha subunits of all 3 cell lines to varying degrees, suggesting the presence of N-linked glycosylation. Insulin induced autophosphorylation of the insulin receptor beta subunit in WGA-purified membranes from all 3 cell lines. In addition, phosphorylation of a protein with an apparent mol. wt. 105 kDa was stimulated by insulin in WGA purified membranes from NG108. Tyrosine-specific kinase activity was present in the membranes from each cell line and was stimulated by insulin in a dose-dependent manner from 10(-9) to 10(-6) M. Proinsulin was about 100 times less potent in stimulating phosphorylation of the artificial substrate poly (Glu, Tyr)4:1 when compared to insulin in accordance with its lower binding affinity to the insulin receptor. Hexose transport was stimulated by insulin in all 3 cell lines. These results indicate that neuroblastoma cells contain specific insulin receptors and that they may be useful as models for studying the role of insulin in nervous tissue.
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PMID:Characterization of the altered oligosaccharide composition of the insulin receptor on neural-derived cells. 335 62

The effect of serum and temperature elevation on proliferation has been studied in synchronized mouse neuroblastoma (Neuro-2A) cells. The effects of serum were studied on the induction of (a) mitotic delay due to a non-lethal heat treatment (30 min at 42.7 degrees C) and (b) the loss of colony-forming capacity after a more extensive heat treatment (45 min at 44 degrees C or a continuous 42.7 degrees C heat treatment). The following results were obtained. Under conditions of serum depletion, cell cycle extension of heated G1 phase cells was more than that of heated G2 phase cells. Serum protected against heat-induced alterations of cell cycle progression in G1- but not in G2 phase cells. This effect of serum could be mimicked by a supplement to the medium of human transferrin, bovine pancreas insulin and selenium, and was correlated with protection of protein synthesis. Serum also affected heat-induced cell killing. Under conditions of serum depletion, G1 phase cells were more resistant to heat compared to G2 cells. The presence of serum during heat treatment further increased the thermoresistance of G1 phase cells, but did not affect sensitivity of G2 phase cells. This effect of serum could not be mimicked by a supplement of transferrin, insulin and selenium. These results indicate that serum protects G1 phase cells for heat-induced changes of cell cycle progression as well as on cell survival, but the mechanisms involved in both phenomena seem to be different.
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PMID:Effect of serum on heat response of synchronized mouse neuroblastoma cells: protection of cell cycle progression, protein synthesis and survival. 348 27

The central nervous system manifests complex homeostatic mechanisms for the maintenance of thyroid hormone economy. The present studies used the NB41A3 mouse neuroblastoma cell line as a model system to study the hormonal regulation of the enzymatic conversion of T4 to T3 in neural tissue. NB41A3 cells manifested a thiol-dependent 6-n-propyl-2-thiouracil-insensitive iodothyronine 5'-deiodinase (I5'D) with a Km for T4 of approximately 10 nM. I5'D activity was increased 2- to 4-fold in cells grown in thyroid hormone-depleted medium. Exposure of cells in situ to various thyroid hormones resulted in a rapid dose-dependent inhibition of enzyme activity with the following order of potency: rT3 = T4 greater than T3. The potent inhibitory effect of rT3 on I5'D activity could not be attributed to substrate competition with T4 in the reaction assay. The addition of dexamethasone (2 X 10(-7) M) to the culture medium also inhibited I5'D activity by 46 +/- 6% (+/- SE; n = 4 experiments; P less than 0.02), whereas insulin and epinephrine were without effect. In other experiments, saturation analysis using a purified preparation of isolated nuclei from NB41A3 cells demonstrated the presence of saturable, high affinity nuclear binding sites which had a Kd value for T3 of 0.13 +/- 0.05 nM and a maximum binding capacity of 0.13 +/- 0.01 pmol T3/mg DNA. These studies demonstrate that NB41A3 cells have a low Km (type II) I5'D process and nuclear T3-binding sites very similar to those previously described in the rat central nervous system. I5'D activity in this cell line appears to be regulated by multiple serum factors, including thyroid hormones and glucocorticoids. The potent regulatory effect of rT3 and T4 suggests that T3 formation by thyroid hormones in neural tissue is controlled by a unique cellular mechanism independent of the nuclear T3 receptor. Since tissue and plasma concentrations of T4 are considerably higher than those of rT3, the former hormone is likely to be the principal thyroid hormone regulating this enzymatic process.
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PMID:Hormonal control of a low Km (type II) iodothyronine 5'-deiodinase in cultured NB41A3 mouse neuroblastoma cells. 352 24

We report that nerve growth factor (NGF) can elevate tubulin transcript levels in cultured rat pheochromocytoma PC12 cells in a manner which correlates with its capacity to enhance neurite formation. The elevation is due, at least in part, to transcript stabilization. We have previously shown that insulin and its homologs can similarly enhance neurite outgrowth and tubulin mRNA levels in human neuroblastoma cells. Insulin by itself can neither induce neurite formation nor increase tubulin transcript levels in PC12 cells. However, both responses are potentiated in cells treated with the combination of insulin and NGF. The results together support the generalization that tubulin transcript levels are specifically elevated whenever neurite elongation is initiated by polypeptide neuritogenic factors.
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PMID:Nerve growth factor modulates tubulin transcript levels in pheochromocytoma PC12 cells. 368 39

Insulin receptors were detected in a variety of rat neuroblastoma and glioma cell lines. The binding of 125I-insulin to B103 neuroblastoma cells had characteristics typical of insulin receptors in other tissues, including high affinity for insulin, low affinity for insulin-like growth factor I (IGF-I), and curvilinear Scatchard plots. Using photoaffinity labeling procedures and sodium dodecyl sulfate (SDS) gel electrophoresis to analyze the subunit structure of insulin receptors in B103 cells, the predominantly labeled protein had an apparent molecular weight of 125K and the mobility of this protein was shifted after removal of sialic acid residues. On the basis of size and susceptibility to neuraminidase, the insulin binding subunit in neuroblastoma cells was identical to the alpha-subunit of insulin receptors in adipocytes and different from the 115K subunit found in brain. The presence of an "adipocyte" form of the insulin receptor in clonal cells derived from brain is probably a consequence of transformation and results from more extensive oligosaccharide processing of the 115K receptor expressed in normal brain cells. The fully glycosylated receptors in neuroblastoma cells were capable of exerting functions typical of insulin receptors in adipocytes such as internalization of insulin and stimulation of glucose transport.
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PMID:Structural and functional characteristics of insulin receptors in rat neuroblastoma cells. 390 Feb 95

We have previously shown that insulin and the insulin-like growth factors share some important neurotrophic properties with nerve growth factor (NGF), including the capacity to enhance neurite formation. In this study, we have examined the effects of these neuritogenic agents on the expression of genes coding for important cytoskeletal proteins of axons and dendrites. Insulin specifically and coordinately increased the levels of alpha- and beta-tubulin mRNAs in human neuroblastoma SH-SY5Y cells. The dose-response curves for these increases were very similar to that for enhancement of neurite formation. Tubulin transcripts reached a transient maximum in approximately 1 day, suggesting that higher levels are important during initiation of neurites and that high levels are not required to sustain neurites once formed. Insulin-like growth factor II shared with insulin the capacity to substantially increase tubulin mRNA levels. NGF had but a small effect. Complementary mechanisms for these neurotrophic agents are suggested, because other studies show NGF and insulin can synergistically potentiate neurite formation. None of the factors altered the levels of actin mRNA. Thus, neurite formation does not seem to require a coordinate increase in actin and tubulin transcripts in SH-SY5Y cells.
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PMID:Insulin, insulin-like growth factor II, and nerve growth factor effects on tubulin mRNA levels and neurite formation. 390 Oct 11

A trypsin-degradable nerve growth factor (NGF) receptor associated with the phospholipid component of the surface membrane has been detected on F98 anaplastic glioma cells. NGF also bound to the nucleus of F98 cells. Bound NGF was not displaceable by insulin, cytochrome C, growth hormone, or bovine serum albumin. Specific binding of NGF occurred with a Kd of 8.79 X 10(-12) M as determined by Scatchard analysis with approximately 34,000 receptors per cell. Specific NGF binding was also evident to C6 rat glioma cells and IMR-32 human neuroblastoma cells, but not to 3T3 mouse fibroblasts. These observations coupled with previous findings suggest that the NGF receptor may be a marker found on cells of neural derivation. As little as 1 ng/ml NGF caused an increase in the adhesiveness of F98 cells to culture flasks. Increased adhesiveness could be observed in as little as 5 min and was apparent for at least 45 min. At 25 min in NGF-containing medium, 24 +/- 3% of the cells adhered to the flasks compared to 13 +/- 1% of control cells. The NGF-induced increase in adhesiveness was not duplicated by epidermal growth factor, insulin, cytochrome c, bovine serum albumin, dibutyryl cyclic AMP, or sodium butyrate. Oxidized NGF blocked the effect of native NGF, but had little or no adhesion-promoting activity itself. Pretreatment of the cells with NGF was also effective in promoting adhesion, even though nerve growth factor was not added to the binding medium. The effect of this pretreatment was reversible; when NGF-pretreated cells were grown in medium without supplemental NGF, the adhesiveness of the cells returned to control levels or lower.
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PMID:Increased adhesion response of anaplastic glioma cells to nerve growth factor and the presence of specific receptors. 631 24

In serum-free medium, SH-SY5Y human neuroblastoma cells specifically and reversibly lost the capacity to bind 125I-labeled nerve growth factor (NGF) to the high-affinity sites (slow sites) and to respond by neurite outgrowth, unless physiological concentrations of insulin or insulin-like growth factor II were present. In serum-containing medium, anti-insulin antiserum decreased the neurite formation response to NGF, and insulin supplementation increased the number of available NGF slow sites. The low-affinity NGF fast sites are absent from SH-SY5Y cells and did not emerge on treatment with insulin. Insulin potentiated the induction of neurites by NGF in rat pheochromocytoma PC12 cells also. These results implicate a wider role for insulin and its homologs in the nervous system.
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PMID:Insulin and insulin-like growth factor II permit nerve growth factor binding and the neurite formation response in cultured human neuroblastoma cells. 632 32

The identification of biologically important and chemically well-defined substances that can promote axon and dendrite formation would improve present understanding of the development of the nervous system. Physiological concentrations of insulin and insulin-like growth factor-II (IGF-II) reversibly enhanced neurite outgrowth (NTO) in human neuroblastoma SH-SY5Y cells cultured in media with and without serum. Nerve growth factor (NGF), in contrast, did not enhance NTO in serum-free media. Furthermore, anti-NGF antiserum inhibited NGF but not insulin-enhanced NTO. Insulin increased [3H]leucine and [3H]uridine uptake. These increases, together with increased NTO, were inhibited by cycloheximide and actinomycin D, respectively. The inhibition of NTO by cycloheximide was reversible. Human neuroblastoma cell lines that were responsive by NTO to NGF were also responsive to insulin, with the exception of line CHP-270. Moreover, cell lines unresponsive by NTO to NGF, and to tumor promoters, were uniformly unresponsive to insulin. These findings suggest that there are common defects in distal sites, because specific NGF and tumor promotor receptors are present in these lines. Insulin increased [3H]thymidine uptake in SH-SY5Y and CHP-100 cells. However, the enhancement of NTO by insulin and IGF-II in SH-SY5Y cells was independent of the cellular proliferation rate. Our results, together with the observations of others, suggest that insulin and IGF-II may modulate NTO in the nervous system.
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PMID:Effects of insulin, insulin-like growth factor-II and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells. 632 60


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