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

The phosphatidylserine (PtdSer) content of human cholinergic neuroblastoma (LA-N-2) cells was manipulated by exposing the cells to exogenous PtdSer, and the effects on phospholipid content, membrane composition, and incorporation of choline into phosphatidylcholine (PtdCho) were investigated. The presence of liposomes containing PtdSer (10-130 microM) in the medium caused time- and concentration-dependent increases in the PtdSer content of the cells, and smaller and slower increases in the contents of other membrane phospholipids. The PtdSer levels in plasma membrane and mitochondrial fractions prepared by discontinuous sucrose density gradient centrifugation increased by 50 and 100%, respectively, above those in control cells after 24 h of exposure to PtdSer (130 microM). PtdSer caused a concomitant, concentration-dependent increase of up to twofold in the incorporation of [methyl-14C]choline chloride into PtdCho at a choline concentration (8.5 microM) compatible with activation of the CDP-choline pathway, suggesting that the levels of PtdSer in membranes may serve as a stimulus to regulate overall membrane composition. PtdSer caused a mean increase of 41% in PtdCho labeling, but the phorbol ester, phorbol 12-myristate 13-acetate (PMA), which stimulates PtdCho synthesis in a number of cell lines, increased [14C]PtdCho levels by only 14% in LA-N-2 cells, at a concentration (100 nM) which caused complete translocation of the calcium- and phospholipid-dependent enzyme protein kinase C to the membrane. The translocation was inhibited by prior exposure of the cells to PtdSer. Treatment with PMA for 24 h diminished protein kinase C activity by 80%, but increased the labeling of PtdCho in both untreated and PtdSer-treated cells. These data suggest that uptake of PtdSer by LA-N-2 cells alters both the phospholipid composition of the membrane and synthesis of the major membrane phospholipid PtdCho; the latter effect does not involve activation of protein kinase C.
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PMID:Uptake of exogenous phosphatidylserine by human neuroblastoma cells stimulates the incorporation of [methyl-14C]choline into phosphatidylcholine. 274 33

The effects of putative transmethylation inhibitors were tested on stimulus-secretion coupling and neurotransmitter secretion at synapses between neuroblastoma X glioma hybrid cells and myotubes. 5'-Deoxy-5'-isobutylthio-3-deazaadenosine or 5'-deoxy-5'-isobutylthioadenosine inhibited CDP-choline synthesis catalyzed by cholinephosphate cytidylyltransferase (CTP:cholinephosphate cytidylyltransferase, EC 2.7.7.15) and thereby decreased the rate of phosphatidylcholine synthesis from CDP-choline, but did not affect the transmethylation pathway for phosphatidylcholine synthesis. These compounds also inhibited 45Ca2+ uptake by hybrid cells mediated by voltage-sensitive Ca2+ channels, acetylcholine secretion at synapses, and signal transduction through cell membranes mediated by myotube nicotinic acetylcholine receptors. In contrast, 3-deazaadenosine or adenosine inhibited the transmethylation pathway for phosphatidylcholine synthesis, but had no effect on Ca2+ action potentials, acetylcholine secretion, or signal transduction through cell membranes mediated by nicotinic acetylcholine receptors. These results show that the stimulus-secretion coupling and secretion reactions studied are not dependent on phospholipid methylation and suggest that the activity of action potential Ca2+ channels and the rate of neurotransmitter secretion are functionally coupled to the rate of phosphatidylcholine synthesis via the CDP-choline pathway.
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PMID:Inhibitors of CDP-choline synthesis, action potential calcium channels, and stimulus-secretion coupling. 608 19

The effect of dihydroergocristine on energy metabolism was studied in the isolated perfused rat brain affected by ischemia and in cultivated C-1300 neuroblastoma cells deprived of oxygen and glucose. Creatine phosphate, ATP, ADP, AMP, glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate were measured enzymatically. After a perfusion period of 30 min, the cortex of the isolated perfused rat brain exhibited an energy state not different from that in vivo. Dihydroergocristine added to the perfusion medium (5 mumol/L) did not influence these substrate levels under normal perfusion conditions. However, this drug was able to retard the breakdown of high-energy phosphates during ischemia and to accelerate the restoration of the energy state during the postischemic reperfusion period. The perfusion rate was not changed by the drug, and therefore it was assumed that dihydroergocristine could act directly on cell metabolism. This view was supported by the results obtained from experiments using cultivated N-2a neuroblastoma cells. These cells were incubated in a buffered salt solution deprived of glucose and oxygen for 15 min. Under these conditions, dihydroergocristine (2 mumol/L) added to the incubation medium caused changes in the concentrations or the high-energy phosphates similar to those in the isolated brain preparation: It increased the ATP concentration and decreased the ADP concentration significantly.
J Cereb Blood Flow Metab 1984 Dec
PMID:Effect of dihydroergocristine on energy metabolism studied in the isolated perfused rat brain affected by ischemia and in neuroblastoma cells deprived of oxygen and glucose. 643 25

Dansylcadaverine, amantadine, and rimantadine, which have been shown to inhibit the endocytosis of alpha 2-macroglobulin, epidermal growth factor, and vesicular stomatitis virus [Schlegel, R., Dickson, R. B., Willingham, M. C. & Pastan, I. (1982) Proc. Natl. Acad. Sci. USA 79, 2291-2295], were found to decrease phosphatidylcholine synthesis, chemotaxis, and internalization of a formylated peptide but to stimulate the incorporation of inositol into phosphatidylinositol in rabbit neutrophils. Dansylcadaverine decreased phosphatidylcholine synthesis by both the CDP-choline and transmethylation pathways and also inhibited the synthesis of phosphatidylethanolamine by the CDP-ethanolamine pathway. Dansylcadaverine had no effect on the phosphocholine, CDP-choline, or S-adenosyl-L-homocysteine pools but increased 2-fold the S-adenosyl-L-methionine pool. These results suggest that dansylcadaverine in some manner inhibited the condensation of CDP-choline with diacylglycerol to form phosphatidylcholine. Dansylcadaverine also inhibited phosphatidylcholine synthesis in human neutrophils, human fibroblasts, chicken embryo fibroblasts, rat hepatocytes, osteosarcoma cells, and neuroblastoma cells. It did not stimulate phosphatidylinositol synthesis in chicken embryo fibroblasts.
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PMID:Inhibitors of endocytosis perturb phospholipid metabolism in rabbit neutrophils and other cells. 657 51

In brain and nerves the phosphorylation of glucose, rather than its transport, is generally considered the major rate-limiting step in metabolism. Since little is known regarding the kinetic coupling between these processes in neuronal tissues, we investigated the transport and phosphorylation of [2-3H]glucose in two neuronal cell models: a stable neuroblastoma cell line (NCB20), and a primary culture of isolated rat dorsal root ganglia cells. When transport and phosphorylation were measured in series, phosphorylation was the limiting step, because intracellular glucose concentrations were the same as those outside of cells, and because the apparent Km for glucose utilization was lower than expected for the transport step. However, the apparent Km was still severalfold higher than the Km of hexokinase I. When [2-3H]glucose efflux and phosphorylation were measured from the same intracellular glucose pool in a parallel assay, rates of glucose efflux were three- to-fivefold greater than rates of phosphorylation. With the parallel assay, we observed that activation of glucose utilization by the sodium channel blocker veratridine caused a selective increase in glucose phosphorylation and was without effect on glucose transport. In contrast to results with glucose, both cell types accumulated 2-deoxy-D-[14C]glucose to concentrations severalfold greater than extracellular concentrations. We conclude from these studies that glucose utilization in neuronal cells is phosphorylation-limited, and that the coupling between transport and phosphorylation depends on the type of hexose used.
J Cereb Blood Flow Metab 1995 Sep
PMID:Coupled glucose transport and metabolism in cultured neuronal cells: determination of the rate-limiting step. 767 74

The electrophoretic pattern of laddered DNA fragments which has been observed after cerebral ischemia is considered to indicate that neurons are dying by apoptosis. Herein the authors directly demonstrate using ligation-mediated polymerase chain reaction methods that 99% of the DNA fragments produced after either global or focal ischemia in adult rats, or produced after hypoxia-ischemia in neonatal rats, have staggered ends with a 3' recess of approximately 8 to 10 nucleotides. This is in contrast to archetypal apoptosis in which the DNA fragments are blunt ended as seen during developmental programmed cell death in dying cortical neurons, neuroblastoma, or thymic lymphocytes. It is not simply ischemia that results in staggered ends in DNA fragments because ischemic myocardium is similar to archetypal apoptosis with a vast majority of blunt-ended fragments. It is concluded that the endonucleases that produce this staggered fragmentation of the DNA backbone in ischemic brain must be different than those of classic or type I apoptosis.
J Cereb Blood Flow Metab 1999 May
PMID:Cerebral ischemia produces laddered DNA fragments distinct from cardiac ischemia and archetypal apoptosis. 1032 17

Recent evidence suggests that stress-activated protein kinases expressed in glial cells have very important roles during cerebral ischemia. The neuroprotective agent chlomethiazole, which is known to enhance the conductance at the GABA(A) receptor complex, is presently in clinical trials for the treatment of severe stroke. Here the authors suggested that chlormethiazole has anti-inflammatory properties because it potently and selectively inhibited p38 mitogen-activated protein (MAP) kinase in primary cortical glial cultures. The inhibition of p38 MAP kinase resulted in the attenuation of the induction of c-fos and c-jun mRNA and AP-1 DNA binding by lipopolysaccharide (LPS). In addition, chlomethiazole inhibited the activation of an AP-1-dependent luciferase reporter plasmid in SK-N-MC human neuroblastoma cells in response to glutamate. Chlomethiazole inhibited the p38 MAP kinase activity as revealed by the decrease in the LPS-induced phosphorylation of the substrates ATF-2 and hsp27, whereas the phosphorylation status of the p38 MAP kinase itself was unaffected. Interestingly, chlomethiazole exhibited an IC(50) of approximately 2 micromol/L for inhibition of c-fos mRNA expression, indicating 25 to 75 times higher potency than reported EC(50) values for enhancing GABA(A) chloride currents. The results indicated a novel mechanism of action of chlomethiazole, and provided support for a distinctive role of p38 MAP kinase in cerebral ischemia.
J Cereb Blood Flow Metab 2000 Jul
PMID:Neuroprotective agent chlomethiazole attenuates c-fos, c-jun, and AP-1 activation through inhibition of p38 MAP kinase. 1090 41

The agonist stimulation of a variety of cells results in the induction of specific lipid metabolism in nuclear membranes, supporting the hypothesis of an important role of the lipids in nuclear signal transduction. While the existence of a phosphatidylinositol cycle has been reported in cellular nuclei, little attention has been given to the metabolism of phosphatidylcholine in nuclear signaling. In the present study the metabolism of phosphatidylcholine in the nuclei of neuroblastoma cells LA-N-1 was investigated. The incubation of LA-N-1 nuclei with radioactive choline, phosphocholine or CDP-choline led to the production of labelled phosphatidylcholine. The incorporation of choline and phosphocholine but not CDP-choline was enhanced in nuclei of TPA treated cells. Moreover the presence of choline kinase, phosphocholine cytidylyltransferase and phosphocholine transferase activities were detected in the nuclei and the TPA treatment of the cells stimulated the activity of the phosphocholine cytidylyltransferase. When cells prelabelled with [3H]palmitic acid were stimulated with TPA in the presence of ethanol, an increase of labelled diacylglycerol and phosphatidylethanol in the nuclei was observed. Similarly, an increase of labelled diacylglycerol and phosphatidic acid but not of phosphatidylethanol occurred in [3H]palmitic acid prelabelled nuclei stimulated with TPA in the presence of ethanol. However the production of phosphatidylethanol was observed when the nuclei were treated with TPA in the presence of ATP and GTPgammaS. The stimulation of [3H]choline prelabelled nuclei with TPA also generated the release of free choline and phosphocholine. The results indicate the presence of PLD and probably PLC activities in LA-N-1 nuclei and the involvement of phosphatidylcholine in the production of nuclear lipid second messengers upon TPA stimulation of LA-N-1 cells. The correlation of the disappearance of phosphatidylcholine, the production of diacylglycerol and phosphatidic acid with the stimulation of phosphatidylcholine synthesis in nuclei of TPA treated LA-N-1 suggests the existence of a phosphatidylcholine cycle in these nuclei.
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PMID:Phosphatidylcholine metabolism in nuclei of phorbol ester-activated LA-N-1 neuroblastoma cells. 1105 44

Chromatin-associated phospholipids are well recognized. A report that catalytically active endonuclear CTP:choline-phosphate cytidylyltransferase alpha is necessary for cell survival questions whether endonuclear, CDP-choline pathway phosphatidylcholine synthesis may occur in situ. We report that chromatin from human IMR-32 neuroblastoma cells possesses such a biosynthetic pathway. First, membrane-free nuclei retain all three CDP-choline pathway enzymes in proportions comparable with the content of chromatin-associated phosphatidylcholine. Second, following supplementation of cells with deuterated choline and using electrospray ionization mass spectrometry, both the time course and molecular species labeling pattern of newly synthesized endonuclear and whole cell phosphatidylcholine revealed the operation of spatially separate, compositionally distinct biosynthetic routes. Specifically, endogenous and newly synthesized endonuclear phosphatidylcholine species are both characterized by a high degree of diacyl/alkylacyl chain saturation. This unusual species content and synthetic pattern (evident within 10 min of supplementation) are maintained through cell growth arrest by serum depletion and when proliferation is restored, suggesting that endonuclear disaturated phosphatidylcholine enrichment is essential and closely regulated. We propose that endonuclear phosphatidylcholine synthesis may regulate periodic nuclear accumulations of phosphatidylcholine-derived lipid second messengers. Furthermore, our estimates of saturated phosphatidylcholine nuclear volume occupancy of around 10% may imply a significant additional role in regulating chromatin structure.
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PMID:Highly saturated endonuclear phosphatidylcholine is synthesized in situ and colocated with CDP-choline pathway enzymes. 1112 19

To determine the role of calcium homeostasis in ischemic neuronal death, the authors used an in vitro model of oxygen-glucose deprivation in neuronal cell lines. Exposure of human neuroblastoma SH-SY5Y cells to 10-to 16-hour oxygen-glucose deprivation decreased viability to 50% or less, and longer exposure times killed almost all cells. The death following 10-to 16-hour oxygen-glucose deprivation was not manifested until 24 to 72 hours after exposure. Deprivation of both glucose and oxygen together was required for expression of toxicity at these exposure times. Dantrolene, which blocks the release of endoplasmic reticulum Ca2+ stores, partially protected SH-SY5Y cells from oxygen-glucose deprivation toxicity. The addition of dantrolene during the deprivation phase alone produced the maximal drug effect; no further protection was obtained by continued drug exposure during the recovery phase. Prevention of Ca2+ influx by chelation or channel blockade or the chelation of cytosolic Ca2+ did not inhibit oxygen-glucose deprivation toxicity. In contrast, increasing extracellular Ca2+ or stimulating Ca2+ influx did inhibit toxicity. Calcium measurements with fura-2 acetoxymethylester revealed that oxygen-glucose deprivation caused a significant reduction in thapsigargin-releasable endoplasmic reticular stores of Ca2+. These studies suggest that an important component of the neuronal toxicity in cerebral ischemia is due to disruption of calcium homeostasis, particularly to the depletion of intracellular Ca2+ stores.
J Cereb Blood Flow Metab 2002 Feb
PMID:Role of intracellular calcium stores in cell death from oxygen-glucose deprivation in a neuronal cell line. 1182 18


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