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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of diabetic neuropathy is incompletely understood. The possibility that humoral neurotoxic factors contribute as a cause of diabetic neuropathy was tested by application of serum from patients with Type 1 and Type 2 diabetes to mouse neuroblastoma cells, which have the characteristics of adrenergic neurons in culture. Serum from patients with Type 1 diabetes and somatic neuropathy significantly inhibited both proliferation and differentiation of neuroblastoma cells, while serum from patients with Type 1 diabetes but no symptoms of neuropathy and patients with Type 2 diabetes and neuropathy had no effect on proliferation, and serum from Type 2 patients only marginally inhibited differentiation. The effects of Type 1 diabetic serum could be reversed by pre-absorption of the serum to neuroblastoma cells, and were independent of glucose levels. Immunoglobulins precipitated from the sera mimicked the effects of whole sera. These results suggest that Type 1 diabetes mellitus causes a change in serum composition, possibly related to autoimmunity, that is capable of contributing to adrenergic autonomic neuropathy in diabetic patients.
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PMID:The toxic effects of serum from patients with type 1 diabetes mellitus on mouse neuroblastoma cells: a new mechanism for development of diabetic autonomic neuropathy. 830 88

To investigate choline phospholipid metabolism in the human neuroblastoma cell line SH-SY5Y, cultures labeled with [14C-methyl]choline were incubated for up to 30 min in Krebs-Ringer-glucose-N-2-hydroxyethyl-piperazine-N1-2-ethane sulfonic acid (HEPES) buffer with or without 10 mmol/L LiCl. When desired, 1 mmol/L of the muscarinic agonist carbamoylcholine was present during the last minute of incubation. When cells were exposed for 10 min to lithium, radioactivity in phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin was 40%-140% higher than in controls incubated in buffer only. This contrasted with the results from carbamoylcholine-containing incubations, which gave radioactivities lower than or equal to controls. Carbamoylcholine added to the LiCl-containing incubations yielded results only minimally different from LiCl alone. Phosphorylcholine radioactivity was also elevated by about 50% after 10 min incubation with LiCl with or without added carbamoylcholine, but was not increased in incubations with the agonist by itself. Similar changes were observed for intracellular choline but after only 5 min. These data suggest that carbamoylcholine does not stimulate phosphatidylcholine degradation, whereas LiCl can significantly affect its metabolism and may affect signal transduction via second messengers in human neuroblastoma cells.
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PMID:Alterations in the metabolism of choline-containing phospholipids by lithium and carbachol in SH-SY5Y neuroblastoma cells. 837 38

myo-Inositol accumulation and incorporation into phosphoinositides was decreased in neuroblastoma cells chronically exposed to medium containing 30 mmol/L glucose or 30 mmol/L galactose. In addition, the intracellular content of myo-inositol and phosphatidylinositol was decreased and the sorbitol or galactitol content increased in cells cultured for 2 weeks in medium containing 30 mmol/L glucose or 30 mmol/L galactose, respectively. Na+/K+ adenosine triphosphatase (ATPase) transport activity was also significantly decreased by long-term exposure of neuroblastoma cells to medium containing 30 mmol/L glucose or 30 mmol/L galactose. When glucose-conditioned cells were placed in medium containing a normal glucose concentration for 24 hours, myo-inositol metabolism and content, phosphatidylinositol levels, and Na+/K+ pump activity were restored or completely returned to normal values. These functions were also significantly improved, except for the phosphatidylinositol content, which was increased by 55%, when galactose-conditioned cells were incubated for 24 hours in unsupplemented medium. The polyol content of the glucose- or galactose-conditioned cells was also significantly reduced. Returning the cells to normal glucose levels for 1 to 3 hours did not completely restore myo-inositol metabolism. Improved myo-inositol metabolism and content, sorbitol levels, and Na+/K+ ATPase transport activity were also obtained within 24 hours when cells chronically exposed to medium supplemented with 30 mmol/L glucose were placed in medium containing 30 mmol/L glucose and 0.4 mmol/L sorbinil. The phosphatidylinositol content of these cells was improved by approximately 30%. Cells prelabeled for 24 hours with [U-14C]sorbitol metabolize more than 50% of the [U-14C]sorbitol during a 24-hour incubation in unsupplemented medium. These studies conducted at the cellular level suggest that restoration of normal myo-inositol metabolism, polyol content, and Na+/K+ pump activity altered by hyperglycemic conditions occurs rapidly following normalization of glucose concentration.
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PMID:Reversal of hyperglycemic-induced defects in myo-inositol metabolism and Na+/K+ pump activity in cultured neuroblastoma cells by normalizing glucose levels. 841 73

Radionuclides are applied in oncology for diagnosis and therapy. The former demands gamma--emitting radionuclides for labeling specific substrates for localizing malignant tissue and for analyzing tumor metabolism in vivo. Here, positron emission tomography (PET) may register in vivo the metabolism, for example, of glucose, amino acids, and receptors and of potentially useful cytotoxic agents. The advantage of the positron emitting radionuclides of carbon, nitrogen and fluorine is the labeling of substrates without changing substrate specificity within the metabolic reaction chain; also, substrate concentration in situ may be quantified. With regard to therapy radionuclides that emit beta- and alpha-particles or decay by electron capture with the Auger effect, are administered in ionic form or with tumor seeking substrates. Examples are radioiodine for treating thyroid malignancy and radiophosphorus for myeloproliferative diseases. Organically bound radionuclides are given as labeled ligands for specific receptors, such as meta-iodo-benzylguanidine (MIBG) for treating the catecholamine producing tumors phaeochromocytoma and neuroblastoma and labeled monoclonal antibodies for tumors specific receptors. Highly localized energy depositions come from Auger emitters such as 125I and by the neutron capture therapy, where boron-10 in the tumor cell is exposed to thermal neutrons for initiating the B10 (n; alpha) Li7 reaction, especially for treating neuro- and glioblastoma and melanoma. Endogenous radiotherapy with radionuclides rely on the success of delivering a proper amount of energy into individual tumor cells with optimal protection of normal tissue. The inevitable heterogeneity of energy deposition events from such approaches demands careful dosimetric assessment for which the classical methods of dosimetry for percutaneous radiotherapy are not applicable.
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PMID:Contributions of nuclear medicine to the therapy of malignant tumors. 844 68

Stable expression of neuronal receptors in cell lines of neural origin is important for studies of neurotransmitter mediated signal transduction. We have achieved this for the first time in three cell lines which are derived from various tissues of neural origin (hippocampus, HN2; chinese hamster brain explant, NCB-20; rat dorsal root ganglion, F-11). Following electroporation assisted transfer of a construct containing the hippocampal serotonin 5-HT1A receptor (5-HT1AR) DNA, one neural cell line, NG-108-15 (murine neuroblastoma x C6 glioma), failed to express the transfected activity, while three others as well as the non-neural CHO (chinese hamster ovary) cells expressed high levels of the receptor. Upon normalization to coexpressed human beta-hexosaminidase B activity, it was found that the human 5-HT1AR, which is normally concentrated in the hippocampus and at a lesser density in the brain, was expressed at the highest level (15.7 x 10(4) receptors/cell) in the HN2 followed by the NCB-20 (8.3 x 10(4) receptors/cell), F-11 (4.4 x 10(4) receptors/cell) and lastly the non-neuronal CHO (4.2 x 10(4) receptors/cell) cells. Ten-twelve days after passage, a striking increase in expression of the receptor was observed only in the cell lines of neural origin. By contrast, there was no appreciable increase in expression of the transfected 5-HT1AR in the non-neural CHO cells over time. This late increase in expression was eliminated in cells which had been maintained in low glucose (1 g/L) for the first two days after passage, thus establishing a vital role of glucose in expression of the transfected 5-HT1AR in cell lines of neural origin. In all cases the 5-HT1AR was negatively coupled to adenylate cyclase, as evidenced by an agonist mediated decrease in prostaglandin E1 stimulated cyclic AMP levels.
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PMID:Heterologous expression of the serotonin 5-HT1A receptor in neural and non-neural cell lines. 847 11

Neuroblastoma cells were used to examine the effect of chronic exposure to increased concentrations of glucose, galactose, or L-fucose on bradykinin-stimulated intracellular calcium release using the calcium indicator fluo-3. Bradykinin caused a concentration dependent increase in the intracellular calcium concentration and phosphoinositide hydrolysis in neuroblastoma cells. Norepinephrine, carbachol, serotonin, and thapsigargin also increased the calcium concentration. Treatment of the cells with 10(-6) M bradykinin exhausts calcium release such that the successive treatment of the cells with norepinephrine, carbachol, or serotonin results in no secondary response. In contrast, bradykinin treatment of the cells following exposure to norepinephrine, carbachol, or serotonin caused a secondary increase in calcium release. These results suggest that several hormone responsive calcium pools may exist in neuroblastoma cells or that norepinephrine, carbachol, or serotonin may not fully stimulate calcium release. Bradykinin-stimulated calcium release is not effected by chronic exposure of the cells to increased concentrations of glucose, galactose, or L-fucose. Suggesting that hormone-stimulated calcium release is not an abnormality that develops in neural cells exposed to conditions that mimic the diabetic milieu. In addition, these studies provide evidence that fluo-3 is a good fluorescent indicator for the study of calcium mobilization in cultured neuroblastoma cells.
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PMID:Effect of bradykinin on cytosolic calcium in neuroblastoma cells using the fluorescent indicator fluo-3. 849 91

GRP78, a molecular chaperone expressed in the endoplasmic reticulum, is a "glucose-regulated protein" induced by stress responses that deplete glucose or intracisternal calcium or otherwise disrupt glycoprotein trafficking. Previously we showed that chronic ethanol exposure increases the expression of GRP78. To further understand the mechanism underlying ethanol regulation of GRP78 expression, we studied the interaction between ethanol and classical modulators of GRP78 expression in NG108-15 neuroblastoma x glioma cells. We found that, in addition to increasing basal levels of GRP78 mRNA ("induction"), ethanol produced greater than additive increases in the induction of GRP78 mRNA by the "classical" GRP inducers A23187, brefeldin A, and thapsigargin ("potentiation"). Both the ethanol induction and potentiation responses modulated grp78 gene transcription as determined by stable transfection analyses with the rat grp78 promoter. Ethanol potentiated the action of all classical inducers of grp78 transcription that were studied. In contrast, co-treatment with the classical GRP inducers thapsigargin and tunicamycin produced only simple additive increases in grp78 promoter activity. Transient transfection studies with deletion mutants of the rat grp78 promoter showed that cis-acting promoter sequences required for ethanol induction differ from those mediating responses to classical GRP inducers. Furthermore, linker-scanning mutations of the grp78 promoter suggested that the ethanol potentiation response required a cis-acting promoter element different from those involved in induction by ethanol or classical inducing agents. While the ethanol induction response required 16-24 h to be detectable, ethanol potentiation of thapsigargin occurred within 6 h. The potentiation response also decayed rapidly after ethanol removal. In addition, the protein kinase A inhibitor Rp-cAMPS and protein phosphatase inhibitor okadaic acid both increased ethanol potentiation of thapsigargin while Sp-cAMPS, an activator of protein kinase A, decreased ethanol potentiation. Taken together, our findings suggest two mechanisms by which ethanol regulates grp78 transcription, both differing from the action of classical GRP inducers such as thapsigargin. One mechanism (potentiation) involves a protein phosphorylation cascade and potentiates the action of classical GRP inducers. In contrast, GRP78 induction by ethanol involves promoter sequences and a mechanistic pathway separate from that of the ethanol potentiation response or classical GRP78 inducers. These studies show that ethanol produces a novel and complex regulation of grp78 transcription which could be of particular importance during neuronal exposure to GRP-inducing stressors as might occur with central nervous system injury.
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PMID:Interaction of ethanol with inducers of glucose-regulated stress proteins. Ethanol potentiates inducers of grp78 transcription. 857 45

The metabolism and metabolic effects of succinic acid methyl esters were examined in both NG108-15 mouse neuroblastoma x rat glioma hybrid cells and normal rat brain cells. The conversion of the dimethyl ester of 14C-labeled succinic acid (10 mM) to 14CO2 only represented 5% or less of that found at an equimolar concentration of D-[U- 14C]glucose. Neither the monomethyl nor the dimethyl ester of succinic acid exerted any significant effect upon the metabolism of D-glucose. Likewise, D-glucose (10 mM) failed to significantly affect the oxidation of the dimethyl ester of either [1,4- 14C]succinic acid or [2,3- 14C]succinic acid. It is concluded that, at variance with the situation recently documented in rat pancreatic islets and hepatocytes, the methyl esters of succinic acid are poorly metabolized in neural cells.
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PMID:Metabolism of succinic acid methyl esters in neural cells. 858 55

Defective tissue perfusion and nitric oxide production and altered myo-inositol metabolism and protein kinase C activation have been invoked in the pathogenesis of diabetic complications including neuropathy. The precise cellular compartmentalization and mechanistic interrelationships of these abnormalities remain obscure, and nitric oxide possesses both neurotransmitter and vasodilator activity. Therefore the effects of ambient glucose and myo-inositol on nitric oxide-dependent cGMP production and protein kinase C activity were studied in SH-SY5Y human neuroblastoma cells, a cell culture model for peripheral cholinergic neurons. D-Glucose lowered cellular myo-inositol content, phosphatidylinositol synthesis, and phosphorylation of an endogenous protein kinase C substrate, and specifically reduced nitric oxide-dependent cGMP production a time- and dose-dependent manner with an apparent IC50 of approximately 30 mM. The near maximal decrease in cGMP induced by 50 mM D-glucose was corrected by the addition of protein kinase C agonists or 500 microM myo-inositol to the culture medium, and was reproduced by protein kinase C inhibition or downregulation, or by myo-inositol deficient medium. Sodium nitroprusside increased cGMP in a dose-dependent fashion, with low concentrations (1 microM) counteracting the effects of 50 mM D-glucose or protein kinase C inhibition. The demonstration that elevated D-glucose diminishes basal nitric oxide-dependent cGMP production by myo-inositol depletion and protein kinase C inhibition in peripheral cholinergic neurons provides a potential metabolic basis for impaired nitric oxide production, nerve blood flow, and nerve impulse conduction in diabetes.
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PMID:Modulation of basal nitric oxide-dependent cyclic-GMP production by ambient glucose, myo-inositol, and protein kinase C in SH-SY5Y human neuroblastoma cells. 860 30

To improve the understanding of neuronal cell swelling in cerebral ischemia, cell volume regulation, viability, intracellular electrolytes, and lactate production of Neuro-2A neuroblastoma cells were studied using an in vitro model. The volume regulatory capacity of Neuro-2A cells was assessed after incubation in hypo- and hypertonic media. Anoxia was studied alone and together with inhibition of glycolysis by iodoacetate. Reducing the tonicity of the incubation medium to 250, 200, or 150 mosm/l caused immediate swelling followed by a regulatory volume decrease within 20 min, which, however, was not complete. The final cell volume after regulation depended on the tonicity of the medium and remained above control. There was no regulatory volume increase after cell shrinking in hypertonic media. Despite the severe anisotonic incubation, viability decreased only slightly without reaching statistical significance. In contrast to in vivo conditions, anoxia for 90 min with or without iodoacetate for additional inhibition of anaerobic energy metabolism neither caused neuronal cell swelling nor a decrease of viability. Reoxygenation after the anoxic period also did not induce volume and viability changes. Intracellular K+ of Neuro-2A cells was markedly decreased, while Na+ increased in a 1:1 ratio during complete energy failure by anoxia plus iodoacetate. A similar effect, occurring however somewhat delayed, was seen when the Neuro-2A suspension was exposed to iodoacetate alone. Anoxia without inhibition of glycolysis had no effect on intracellular ion concentrations, but lactate production was nearly six times higher than normal. In vitro, with a large extracellular volume and sufficient glucose supply, the energetic demands of Neuro-2A cells to maintain stable transmembraneous ion gradients during anoxia are obviously met by anaerobic glycolysis. The current results confirm that neuronal cells are able to adequately regulate cell volume in response to hyposmotic stress. On the other hand, maintenance of a normal cell size during complete energy deprivation suggests strongly that energy failure per se does not suffice to induce neuronal swelling. Cell swelling in cerebral ischemia in vivo thus appears a secondary phenomenon due to mediator mechanisms such as tissue acidosis or elevated extracellular glutamate levels.
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PMID:Anoxia in vitro does not induce neuronal swelling or death. 883 70


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