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)

Transporters for the monoamine neurotransmitters, including noradrenaline, 5-hydroxytryptamine [5-HT] and dopamine, have twelve transmembrane spanning regions and cotransport Na+ and Cl- ions. Another family of Na(+)-dependent transporters is that containing the Na+/glucose and Na+/proline cotransporters that are found in the epithelial cells of renal and intestinal brush border membranes. It has been shown that various trivalent lanthanides can substitute for Na+ for transport of glucose and proline. The aim of this study was to determine the effects of lanthanides on the activities of the human noradrenaline, 5-HT and dopamine transporters. Cultured cells were incubated for 2 min with 10 nM 3H-noradrenaline (SK-N-SH-SY5Y human neuroblastoma cells), 3H-5-HT (JAR human placental choriocarcinoma cells) or 3H-dopamine (COS-7 cells transfected with the cDNA of the human dopamine transporter). Specific amine uptake was determined as the difference between accumulation of the amine in the cells in the absence and presence of a corresponding uptake inhibitor. Under both isotonic (150 mM NaCl or LiCl or 90 mM lanthanide salt) and hypertonic (150 mM NaCl +100 mM LiCl, 250 mM LiCl or 150 mM lanthanide salt) conditions, replacement of Na+ by Li+, La3+, Eu3+ or Sm3+ abolished the specific uptake of noradrenaline in SK-N-SH-SY5Y cells and replacement of Na+ by Li+ or Eu3+ decreased the specific uptake of 5-HT in JAR cells by 94-100% and that of dopamine in transfected COS-7 cells by 95-99%. The direct effects of Eu3+ (with Na+ present) on the human noradrenaline transporter in SK-N-SH-SY5Y cells were also examined. Eu3+ inhibited noradrenaline uptake into the cells (IC50 2.6 mM) and nisoxetine binding to crude membranes of SK-N-SH-SY5Y cells (IC50 4.7 mM) with similar potencies. Further experiments showed that 4.5 mM EuCl3 in the presence of 150 mM Na+ caused a 3.5-fold increase in the K(m) of noradrenaline and no change in the maximal rate of noradrenaline uptake. EuCl3 (4.5 mM) also caused a pronounced inhibition of the Na(+)-dependent stimulation of noradrenaline uptake by SK-N-SH-SY5Y cells. It can be concluded from these data that, in contrast with the Na+/glucose and Na+/proline cotransporters, the lanthanides cannot substitute for Na+ in the transport of substrates by the monoamine neurotransmitter transporters and that the lanthanides inhibit the latter transporters by interacting with sites of the transporters involved in amine and Na+ binding.
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PMID:Lanthanides inhibit the human noradrenaline, 5-hydroxytryptamine and dopamine transporters. 920 53

As a new treatment protocol for neuroblastoma, the chimeric (human/mouse) antiganglioside GD2 antibody chl4.18 is being clinically tested. To improve the therapeutic effect of the antibody alone, we are currently investigating the cytotoxicity of glucose-oxidase coupled to the antibody chl4.18 on spheroids of the neuroblastoma cell line SK-N-LO. The cytotoxic effect of glucose-oxidase is achieved by the production of hydrogenperoxide (H2O2) and probably by the following reaction of H2O2 with iron to form hydrogen radicals (OH.). The cytotoxicity of glucose-oxidase was measured by two viability tests (MTT and WST 1). After a 4 hour treatment of the spheroids with the immunoconjugate, a reduction of viability to 50% (MTT-test) and 25% (WST 1-test), respectively, was obtained. The difference between the results of these two tests, might be explained by the different measurement protocols.
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PMID:Cytotoxic effect of immunoconjugate composed of glucose-oxidase coupled to an anti-ganglioside (GD2) antibody on spheroids. 932 30

The present studies were undertaken to determine the role of physiologically relevant concentrations of estrogens on amyloid-induced changes in cell viability, metabolic demands, and lipid peroxidation in response to the toxic fragment of beta-amyloid (betaAP 25-35). To this end, SK-N-SH human neuroblastoma cells were exposed to betaAP 25-35 or betaAP 25-35 plus 17beta-estradiol, and cell viability, media glucose use and lactate production were measured at time points ranging from 3 to 15 h for examination of acute effects, or at 48 and 72 h time points for chronic effects. Addition of betaAP 25-35 to SK-N-SH cells decreased the number of viable cells from 5% at 3 h to 35% at 15 h when compared to vehicle controls. Chronic treatment for 48 and 72 h caused decreases in viable cell number of 70% and 65%, respectively. Paradoxically, both glucose utilization and lactate production were found to be increased for the betaAP-treated cells. Concomitant estrogen treatment was found to be neuroprotective, as the severity of the insult on cell viability was decreased by 40% at 15 h and up to 71% at 72 h. Likewise, the addition of 17beta-estradiol decreased both the glucose use and lactate production of the cells. Chronic treatment with betaAP caused increases in lipid peroxidation over vehicle treated controls of 82% and 78% at 48 and 72 h, respectively, while decreases in peroxidation of 48% were seen with simultaneous estrogen treatment. These results indicate that the neuroprotective effects of estrogens against betaAP-induced toxicity are due in part to their capability to decrease lipid peroxidation and may additionally be attributable to decreasing the metabolic load of the cell.
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PMID:Low concentrations of estradiol reduce beta-amyloid (25-35)-induced toxicity, lipid peroxidation and glucose utilization in human SK-N-SH neuroblastoma cells. 946 88

An isomaltotriose-producing endo-dextranase was simply purified from cell-free culture broth of a Fusarium sp. by ethanol fractionation and consecutive column chromatographies using DEAE-Toyopearl and Bio-Gel P-100. The purified enzyme was judged to be homogeneous on PAGE and SDS-PAGE as well as isoelectric focusing. The molecular mass of the enzyme was estimated to be about 69 kDa by SDS-PAGE. The enzyme is an acidic protein with a pI of 4.6. The optimum pH and temperature were pH 6.5 and 35 degrees C, respectively. The enzyme was completely stable over the range of pH 4.5-11.8 at 4 degrees C for 24 h and at temperatures below 45 degrees C. Inactivation of the enzyme was found to be partial with 5 mM Cu2+, being about 70% inhibition and complete with 5 mM of Fe3+, Hg2+, Ag+ or NBS. The enzyme split dextran in an endo-lytic action to produce a large amount of isomaltotriose and a slight amount of isomaltose and glucose. The anomeric configurations of the reaction products formed by the enzyme were alpha-form, indicating that the alpha-glycoside linkages in the substrate are retained. The final yield of isomaltotriose from dextran T-2000 was about 62%.
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PMID:Purification and characterization of an isomaltotriose-producing endo-dextranase from a Fusarium sp. 950 22

We have previously shown that insulin-like growth factor I (IGF-I) activation of the IGF-I receptor rescues SH-SY5Y human neuroblastoma cells from high glucose-mediated programmed cell death (PCD). In the current study, we further explored the potential points in the cell death cascade where IGF-I receptor activation may afford neuroprotection. As an initial step, we examined the effects of the PCD stimulus, high glucose, on stress-activated protein kinases, specifically the two mitogen-activated protein kinases p38 kinase and c-Jun N-terminal kinase (JNK). High glucose treatment activated the tyrosine phosphorylation of both p38 kinase and JNK in a dose- and time-dependent fashion. We next examined the effects of IGF-I on JNK and p38 kinase under normoglycemic and hyperglycemic conditions. IGF-I activated p38 kinase alone and had additive effects on glucose-induced p38 kinase phosphorylation. In contrast, IGF-I inhibited glucose activation of JNK phosphorylation and JNK activity. IGF-I also inhibited the glucose-induced nuclear translocation of JNK, but did not effect glucose-induced translocation of p38 kinase. Finally, IGF-I inhibition of JNK phosphorylation was blocked by the mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, PD98059. Collectively, these data imply cross-talk between the mitogen-activated protein kinase pathway and JNK and suggest that IGF-I activation of mitogen-activated protein kinases interferes with JNK activation and protects cells from PCD.
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PMID:Bidirectional regulation of p38 kinase and c-Jun N-terminal protein kinase by insulin-like growth factor-I. 960 71

Caspase activation has been shown to be a critical step in several models of neuronal apoptosis such as staurosporine treatment of human neuroblastoma SH-SY5Y cells and potassium deprivation of rat cerebellar granule neurons. One common event is the appearance of caspase-mediated 120-kDa nonerythroid alpha-spectrin breakdown product (SBDP120). Second, inhibitors of the caspase family are effective blockers of such neuronal death. In this study, we report the appearance of caspase-mediated SBDP120 in excitotoxin-challenged fetal rat cerebrocortical neurons [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate] and rat cerebellar granule neurons (NMDA and kainate). A general caspase inhibitor, carbobenzoxy-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-D-DCB), blocked the formation of SBDP120 under these conditions and attenuated the observed NMDA-induced lactate dehydrogenase (LDH) release in both cell types. Furthermore, hydrolytic activity toward a caspase-3-preferred synthetic peptide substrate, acetyl-DEVD-7-amido-4-methylcoumarin, was significantly elevated in NMDA-treated granule neurons. Lastly, oxygen-glucose deprivation (OGD)-challenged cerebrocortical cultures also showed the appearance of SBDP120. Again, Z-D-DCB blocked the SBDP120 formation as well as attenuated the LDH release from the OGD-challenged neurons. Taken together, the presence of caspase-specific SBDP120 and the neuroprotective effects of Z-D-DCB strongly suggest that caspase activation contributes at least in part to excitotoxin- and OGD-induced neuronal death.
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PMID:Evidence for activation of caspase-3-like protease in excitotoxin- and hypoxia/hypoglycemia-injured neurons. 964 65

We investigated the relation between cyclic AMP (cAMP) and nitric oxide (NO) production, as well as the effect of NO on Na , K+-ATPase activity in the human neuroblastoma cell line SH-SY5Y. Two cAMP agonists, dibutyryl cAMP (DBC) and beraprost sodium (BPS), increased cAMP accumulation and NO production in a time and dose dependent manner at 50 mmol/l glucose. On the other hand, cellular sorbitol and myo-inositol contents and protein kinase C activity were not altered by DBC or BPS. A specific protein kinase A inhibitor, H-89, suppressed increases in nitrite/nitrate and cyclic GMP (cGMP) and protein kinase A activity stimulated by DBC or BPS. This finding suggests that cAMP stimulates NO production by activating protein kinase A via a pathway different from the sorbitol-myo-inositol-protein kinase C pathway. We observed that an NO donor, sodium nitroprusside, and an NO agonist, L-arginine, enhanced ouabain sensitive Na+, K+-ATPase activity at 50 mmol/l glucose. We also found that a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), inhibited Na+, K+-ATPase activity at 5 mmol/l glucose, and partially suppressed the enzyme activity stimulated by DBC or BPS. The results of this study suggest that cAMP regulates protein kinase A activity, NO production and ouabain sensitive Na+, K+-ATPase activity in a cascade fashion. The results also suggest that protein kinase A at least partially regulates Na+, K+-ATPase activity without mediation by NO in SH-SY5Y cells. We speculate that cAMP and NO are two important regulatory factors in the pathogenesis of diabetic neuropathy.
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PMID:cAMP regulates nitric oxide production and ouabain sensitive Na+, K+-ATPase activity in SH-SY5Y human neuroblastoma cells. 986 12

The main disadvantages of foetal calf serum as the world-wide common serum supplement for cell growth are its content of various proteins of variable concentrations between batches as well as its high cost. The use of serum-free and protein-free media is gradually becoming one of the goals of cell culture especially for standardizing culture conditions or for simple purification of cell products like monoclonal antibodies. The mouse hybridoma cells 14/2/1 were cultivated either in protein-free UltraDOMA medium or in serum-containing RPMI medium with and without microcarriers to generate high quantities of monoclonal antibodies against neuroblastoma tumour cells. Cell growth rate, IgG production, viability, glucose and lactate concentrations, attachment rate and doubling time have been used as investigation criteria. Modifications of culture procedures (static or stirred), inoculum density, and microcarrier concentration caused an improvement of monoclonal antibody production. The kinetics of antibody synthesis was best in spinner culture with 2 ml of microcarriers in protein-free medium. These results of short-term microcarrier culture in stirred spinner flasks indicate that IgG yields in protein-free medium 2.5-fold higher to those in serum-supplemented medium can be achieved.
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PMID:Hybridoma cell growth and anti-neuroblastoma monoclonal antibody production in spinner flasks using a protein-free medium with microcarriers. 1019 58

The exposure of SY5Y neuroblastoma cells to high concentrations of glucose, fructose, or galactose is an experimental model commonly used for in vitro evaluation of typical neuronal alterations observed in diabetes mellitus. In the present study, we observed that 2 weeks of exposure to high carbohydrate concentrations caused both a significant impairment in neurite formation induced by supplementation of retinoic acid or by subtraction of fetal calf serum to the culture medium and a marked reduction in Na(+)-K(+)-ATPase activity. However, only the exposure to high millimoles of glucose caused an enhancement of mono-ADP-ribosylation, typical of diabetes mellitus, affecting at least five proteins. The concomitant exposure to high glucose and to silybin, a mono-ADP-ribosylation inhibitor, normalized the extent of ADP-ribosylation of the five proteins and counteracted the inhibitory effects of high glucose on Na(+)-pump activity and on neuritogenesis. Conversely, the supplementation of silybin did not prevent fructose and galactose inhibitory effects on Na(+)-pump activity and neurite formation. These data confirm those of previous reports suggesting a link between excessive protein mono-ADP-ribosylation and the onset of diabetic complications such as diabetic neuropathy.
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PMID:Inhibition of high glucose-induced protein mono-ADP-ribosylation restores neuritogenesis and sodium-pump activity in SY5Y neuroblastoma cells. 1046 90

Deficiencies in cellular cyclic AMP (cAMP) and nitric oxide (NO) production are thought to be involved in the pathogenesis of diabetic neuropathy. We used a human neuroblastoma cell line, SH-SY5Y, to investigate the effect of cilostazol, a specific cAMP phosphodiesterase inhibitor, on NO production and Na+, K+-ATPase activity. SH-SY5Y cells were cultured under 5 or 50 mM glucose for 5-6 days, the cells were then exposed to cilostazol or other chemicals and nitrite, cAMP and Na+, K+-ATPase activity were measured. In cells grown in 50 mM glucose, cilostazol was observed to increase significantly both NO production and cellular cAMP accumulation in a time- and dose-dependent manner. Cilostazol also significantly recovered reduced levels of protein kinase A activity (PKA) in 50 mM glucose. Furthermore, a PKA inhibitor, H-89 significantly suppressed the increase in NO production stimulated by cilostazol, suggesting that cilostazol stimulates NO production by activating PKA. Cilostazol did not affect either sorbitol or myo-inositol concentrations. Dexamethasone, which is known to induce inducible NO synthase, had no effect on NO production stimulated by cilostazol, suggesting that cilostazol stimulates NO production catalyzed by neuronal constitutive NO synthase (ncNOS) in SH-SY5Y cells. L-arginine, which is an NO agonist enhanced Na+, K+-ATPase activity in cells grown in 50 mM glucose, NG-nitro-L-arginine methyl ester (L-NAME), which is an NOS inhibitor inhibited basal Na+, K+-ATPase activity in 5 mM glucose and suppressed the increased enzyme activity induced by cilostazol in 50 mM glucose. The above results confirmed our previous observation that NO regulates Na+, K+-ATPase activity in SH-SY5Y cells and suggest that cilostazol increases Na+, K+-ATPase activity, at least in part, by stimulating NO production. The present results also suggest that cilostazol has a beneficial effect on diabetic neuropathy by improving Na+, K+-ATPase activity via directly increasing cAMP and NO production in nerves.
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PMID:Cilostazol, a cyclic AMP phosphodiesterase inhibitor, stimulates nitric oxide production and sodium potassium adenosine triphosphatase activity in SH-SY5Y human neuroblastoma cells. 1050 60


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