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 effect of estradiol-17 beta on the activities of glycolytic enzymes from female rat brain was studied. The following enzymes were examined: hexokinase (HK, EC 2.7.1.1), phosphofructokinase (PFK, EC 2.7.1.11), aldolase (EC 4.1.2.13), glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12), phosphoglycerate kinase (EC 2.7.2.3), phosphoglycerate mutase (EC 2.7.5.3), enolase (EC 4.2.1.11) and pyruvate kinase (PK, EC 2.7.1.40). The activities of HK (soluble and membrane-bound), PFK and PK were increased after 4 h of hormone treatment, while the others remained constant. The changes in activity were not seen in the presence of actinomycin D. The significant rise of the activities of the key glycolytic enzymes was also observed in the cell culture of mouse neuroblastoma C1300 treated with hormone. Only three of the studied isozymes, namely, HKII, B4 and K4 were found to be estradiol-sensitive for HK, PFK and PK, respectively. The results obtained suggest that rat brain glycolysis regulation by estradiol is carried out in neurons due to definite isozymes induction.
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PMID:Rat brain glycolysis regulation by estradiol-17 beta. 153 2

In this study pyruvate kinase, hexokinase and aldolase are investigated in two types of embryonal tumors, neuroblastomas and medulloblastomas; the results are compared with similar studies in gliomas. The activities of hexokinase and pyruvate kinase are significantly decreased in neuroblastomas. In neuroblastoma and medulloblastoma all five forms of pyruvate kinase (K4, K3M, K2M2, KM3 and M4) are present. In contrast, the gliomas investigated are characterized by the presence of mainly K4 and a little K3M. In neuroblastomas, medulloblastomas and gliomas, hexokinase type I is present; in addition, hexokinase type II is present in two medulloblastomas. Aldolase A is the predominant isozyme in all tumors investigated; this is in contrast with normal nervous tissue. It can be concluded that the isozyme characteristics especially of pyruvate kinase from neuroblastomas and medulloblastomas are comparable with similar findings in retinoblastoma; these findings support the hypothesis that these three tumors have a common embryonic origin.
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PMID:Glycolytic enzymes from human neuroectodermal tumors of childhood. 632 86

Six novel alkaloids that contain a fused tetracyclic pyrido[2,3,4-kl]acridine ring system were purified recently from the Red Sea purple tunicate Eudistoma sp. Evaluation of the effects of these alkaloids on cultured neuroblastoma and fibroblast cells revealed that they possess potent growth regulatory properties, and affect cell shape and adhesion. In mouse neuroblastoma cells, the Eudistoma alkaloids inhibited cell proliferation and induced a process of differentiation during which the cells flattened onto the surface, increased considerably in size, and extended long neurites. In hamster fibroblasts the alkaloids slowed down cell multiplication, and caused an exceptional cell flattening or elongation. In a virus-transformed derivative of the hamster fibroblasts the alkaloids restored many aspects of normal cell growth and morphology. In addition, several of the alkaloids mimicked the effects of cAMP analogs on two well-characterized cAMP-mediated processes involved in hepatic glucose metabolism--inhibition of pyruvate kinase (PK) activity and induction of mRNA for phosphoenolpyruvate carboxykinase (PEPCK). All these effects suggest that the Eudistoma alkaloids may act on the cAMP signaling system. However, a single application of these compounds was sufficient to completely block cell multiplication and to induce and sustain differentiation and "reverse transformation". Furthermore, these effects were not readily reversible following removal of the drugs. In contrast, a single application of agents that mimic or elevate cAMP induced a transient response that waned with time in culture, and the effects induced by constant elevation of cAMP reverse rapidly following drug removal. We propose that the Eudistoma alkaloids cause growth inhibition, differentiation, and reverse transformation by modifying the activity state of proteins that are involved in the regulation of cell shape and adhesion and serve as a target for the cAMP and/or other second messenger systems.
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PMID:Novel marine alkaloids from the tunicate Eudistoma sp. are potent regulators of cellular growth and differentiation and affect cAMP-mediated processes. 825 59

This study examines the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on SH-SYSY human neuroblastoma cells cultured in the presence of medium containing varying concentrations of calcium (0.1, 0.9, 1.4, 1.8 mM). Pyruvate kinase activity was assayed in SH-SY5Y cells incubated in variable calcium medium with or without 1, 10 or 100 nM 1,25(OH)2D3 for 48 h. The enzyme levels showed a significant increase in comparison with control, when the cells were incubated with 100 nM hormone in the presence of 0.1 mM calcium, while pyruvate kinase activity decreased, when the cells were treated with 100 nM 1,25(OH)2D3 in the presence of 1.8 mM calcium. The proliferative activity of SH-SY5Y was dependent on the extracellular concentration of calcium, being the highest at 1.8 mM calcium and completely absent at 0.1 mM calcium. In the presence of 1,25(OH)2D3, at the three concentrations used and after 48 h incubation, a significant decrease in cell number was always observed, without a direct correlation between 1,25(OH)2D3 effect and calcium concentration in the medium. [3H]Thymidine incorporation in SH-SY5Y cells significantly increased in comparison with control, when the 48 h incubation with 1, 10 or 100 nM 1,25(OH)2D3 was carried out in the presence of 0.1 mM calcium, while, at the other calcium concentrations, the hormone did not cause any significant change in this parameter. The treatment of SH-SYSY cells with 1 nM 1,25(OH)2D3 for 48 h did not affect cell morphology, when 0.1 mM calcium was present, while, in the medium containing 1.8 mM calcium, the treated cells showed a slight trend to differentiation. The differentiating effect of 10 microM all-trans retinoic acid, even if incomplete after 48 h treatment, was only observed in the cultures grown in 1.8 mM calcium, in comparison with those maintained in 0.1 mM calcium.
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PMID:Role of 1,25-dihydroxyvitamin D3 and extracellular calcium in the regulation of proliferation in cultured SH-SY5Y human neuroblastoma cells. 1034 99

Elevated production of hydrogen peroxide (H2O2) in the central nervous system has been implicated in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, ischemic reperfusion, stroke, and Alzheimer's disease. Pyruvic acid has a critical role in energy metabolism and a capability to nonenzymatically decarboxylate H2O2 into H2O. This study examined the effects of glycolytic regulation of pyruvic acid on H2O2 toxicity in murine neuroblastoma cells. Glycolytic energy substrates including D-(+)-glucose, D-(-) fructose and the adenosine transport blocker dipyridamole, were not effective in providing protection against H2O2 toxicity, negating energy as a factor. On the other hand, pyruvic acid completely prevented H2O2 toxicity, restoring the loss of ATP and cell viability. H2O2 toxicity was also attenuated by D-fructose 1,6 diphosphate (FBP), phospho (enol) pyruvate (PEP), niacinamide, beta-nicotinamide adenine dinucleotide (beta-NAD+), and reduced form (beta-NADH). Both FBP and PEP exerted positive kinetic effects on pyruvate kinase (PK) activity. Interestingly, only pyruvic acid and beta-NADH exhibited powerful stoichiometric H2O2 antioxidant properties. Further, beta-NADH may exert positive effects on PK activity. Subsequent pyruvic acid accumulation can lead to the recycling of beta-NAD+ through lactate dehydrogenase and beta-NADH through glyceraldehyde-3-phosphate dehydrogenase. It was concluded from these studies that intracellular pyruvic acid and beta-NADH appear to act in concert through glycolysis, to enhance H2O2 intracellular antioxidant capacity in neuroblastoma cells. Future research will be required to examine whether similar effects are observed in primary neuronal culture or intact tissue.
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PMID:Cytoprotection of pyruvic acid and reduced beta-nicotinamide adenine dinucleotide against hydrogen peroxide toxicity in neuroblastoma cells. 1271 24

Manganese (Mn) is a trace metal required for normal growth and development. Manganese neurotoxicity is rare and usually associated with occupational exposures. However, the cellular and molecular mechanisms underlying Mn toxicity are still elusive. In rats chronically exposed to Mn, their brain regional Mn levels increase in a dose-related manner. Brain Mn preferentially accumulates in mitochondria; this accumulation is further enhanced with Mn treatment in vivo. Exposure of mitochondria to Mn in vitro leads to uncoupling of oxidative phosphorylation. These observations prompted us to investigate the hypothesis that Mn induces alterations in energy metabolism in neural cells by interfering with the activities of various glycolytic and TCA cycle enzymes using human neuroblastoma (SK-N-SH) and astrocytoma (U87) cells. Treatments of SK-N-SH and U87 cells with MnCl2 induced cell death in these cells, in a concentration- and time-dependent manner, as determined by MTT assays. In parallel with the Mn-induced, dose-dependent decrease in cell survival, treatment of these cells with 0.01 to 4.0 mM MnCl2 for 48 h also induced dose-related decreases in their activities of hexokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase, and malate dehydrogenase. Hexokinase in SK-N-SH cells was the most affected by Mn treatments, even at the lower range of concentrations. Mn treatment of SK-N-SH cells affected pyruvate kinase and citrate synthase to a lesser extent as compared to its effect on other enzymes investigated. However, citrate synthase and pyruvate kinase in U87 cells were more vulnerable than other enzymes investigated to the effects of Mn. The results suggest the two cell types exhibited differential susceptibility toward the Mn-induced effects. Additionally, the results may have significant implications in flux control because HK is the first and highly regulated enzyme in brain glycolysis. Thus these results are consistent with our hypothesis and may have pathophysiological implications in the mechanisms underlying Mn neurotoxicity.
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PMID:Differential lowering by manganese treatment of activities of glycolytic and tricarboxylic acid (TCA) cycle enzymes investigated in neuroblastoma and astrocytoma cells is associated with manganese-induced cell death. 1509 32

Although atypical antipsychotics are widely known to induce alterations in lipid and glucose metabolism, the mechanisms by which these alterations occur remain unknown. Several recent studies have shown that atypical antipsychotics induce oxidative stress and oxidative cell injury by increasing levels of lipid and protein oxidation. In this study, a novel proteomic approach was used to identify specific proteins oxidized after clozapine treatment. Differentiated neuroblastoma SKNSH cells were treated with 0, 5 or 20 mum clozapine for 24 h and protein extracts were labelled with 6-iodoacetamide fluorescein (6-IAF). The lack of incorporation of 6-IAF to cysteine residues is an indicator of protein oxidation. Labelled proteins were exposed to 2D electrophoresis, and differential protein labelling was assessed. Increased oxidation after clozapine treatment was observed in 10 protein spots (p<0.05), although only four of them remained significant after correcting for analysis with two drug concentrations. Five proteins, corresponding to nine of the spots, were identified by HPLC-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) as mitochondrial ribosomal protein S22, mitochondrial malate dehydrogenase, calumenin, pyruvate kinase and 3-oxoacid CoA transferase. The latter four proteins play important roles in energy metabolism. These results suggest that oxidative stress may be a mechanism by which antipsychotics increase the risk for metabolic syndrome and diabetes.
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PMID:Clozapine causes oxidation of proteins involved in energy metabolism: a possible mechanism for antipsychotic-induced metabolic alterations. 1846 68

There is accumulating evidence that oxidative stress plays an important role in aging. Our previous phosphoproteomic study of the human neuroblastoma cell line SH-SY5Y revealed changes in the phosphorylation of several proteins such as lamin A/C during 6-hydroxydopamine-induced oxidative stress. The present study employed native proteomic analysis to clarify protein-protein interaction under physiological conditions. We examined oxidative stress-related changes in SH-SY5Y cellular proteins using blue-native polyacrylamide gel electrophoresis (BN-PAGE), a powerful tool for the separation of protein complexes. BN-PAGE gel images showed successful separation of several complexes. Components of these complexes, separated by 2-D BN-PAGE in combination with SDS-PAGE, were identified by peptide mass fingerprinting employing MALDI-TOF MS and an MS/MS ion search on LC-MS/MS. TCP-1 complex, ATP synthase, and the complex of heat shock protein 90 with its client proteins such as pyruvate kinase were detected. Two dimensional BN-PAGE and Western blot analysis revealed an increase of lamin A/C associated with heat shock protein 90 in response to 6-OHDA-induced oxidative stress.
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PMID:Proteomic analysis of protein complexes in human SH-SY5Y neuroblastoma cells by using blue-native gel electrophoresis: an increase in lamin A/C associated with heat shock protein 90 in response to 6-hydroxydopamine-induced oxidative stress. 1926 20

Neuroblastoma cells, cultivated on plastic dishes, in presence of 15 mM glucose resist very well to hypoxia. Cells incubated on plastic dishes, if left unshaken, showed a Pasteur effect at an oxygen concentration below 10%. Oxygen diffusion was the limiting factor in these plastic dishes since improved oxygen diffusion, as a result of shaking, decreased the lactate production considerably at all oxygen concentrations used. When cells were cultivated on Petriperm((R)) dishes, coated with polylysine, oxygen diffusion was no longer a rate-limiting factor: less lactate was produced at 21% O(2) and hypoxia, down to 2.5% O(2) did not show any increase in the rate of lactate production, while Antimycin A drastically increased the glycolytic rate. A situation of limited oxygen availability resulted in two different kinds of adaptation of the neuroblastoma cells: first an instantaneous metabolic regulation leading to an increased glycolytic rate-the Pasteur effect-followed later by an increase in the activities of the glycolytic enzymes-hexokinase (EC 2.7.1.1), phosphoglucose isomerase (EC 5.3.1.9), 6-phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40) and lactate dehydrogenase (EC 1.1.1.27) and a simultaneous decrease of the mitochondrial cytochrome c oxidase (EC 1.9.3.1) activity. However, when the glucose concentration in the medium was decreased to 5 mM the cells were affected by hypoxia already at 5% O(2): cells released lactate dehydrogenase extracellularly and their protein content was decreased. This toxic effect of hypoxia was related to the exhaustion of the glucose supply.
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PMID:Effect of oxygen and glucose availability on the glycolytic rate in neuroblastoma cells under different conditions of culture. 2048 70

This study analyzed the differences in karyotype and genetic variation between a mutant and wild-type Siraitia grosvenorii. Genetic variation included changes in genome and gene expression by SRAP molecular markers. Results showed that wild-type S. grosvenorii was diploid, with a chromosome number of 2n = 2x = 28, whereas the mutant was tetraploid with a chromosome number of 2n = 4x = 56. 4573 DNA bands were obtained using 189 different primer combinations, 577 of which were polymorphic, averaging 3.1 bands for each primer pair, while 1998 pairs were identical. There were no apparent differences on bands amplified by most primer pairs. After comparing the diploid and tetraploid strains, the data generally indicated that the polymorphism would be quite low. 2917 cDNA bands were generated using 133 primer combinations, and stable and clearly differential fragments were sorted out, cloned and sequenced. Ninety-two differentially expressed fragments were successfully sequenced. Sequence analysis showed that most fragments had significant homologous nucleotide sequences with resistant to stress and photosynthesis genes, including ribulose-1,5-bisphosphate carboxylase/oxygenase, phosphoenolpyruvate carboxykinase, pyruvate kinase, peroxisomal membrane transporter, NBS-LRR type resistance protein, protein phosphatase and others. The results revealed that the tetraploid strain has more resistant and photosynthesis ability than its diploid relatives, which providing reference information and resources for molecular breeding and seedless Luohanguo.
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PMID:Karyotype analysis and genetic variation of a mutant in Siraitia grosvenorii. 2160 54


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