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)

Uremic encephalopathy is a complication of renal failure that reflects stresses exerted by as yet poorly defined uremic toxins. All cells respond to stresses by undergoing the "heat shock" response. Although urea kinetics and creatinine concentration are routinely used to assess dialysis adequacy, the roles of urea and creatinine as uremic toxins remain controversial. To investigate their potential roles in uremic encephalopathy, cultured human neuroblastoma cells (SK-N-SH) were exposed to 0.5 to 14 mg/dL creatinine, or to 20 to 200 mg/dL urea, or to mannitol, NaCl, or glycerol at equivalent osmolalities for 30 min to 48 h, and the induction of Hsp72 (heat shock) protein was used as a marker of cell stress. Although creatinine failed to elicit a heat shock response, urea in clinically relevant concentrations (40 to 200 mg/dL) induced it at 30 min. The response peaked at 10 h and returned to zero by 48 h. Cells exposed to equivalent osmolalities of mannitol, NaCl, or glycerol failed to exhibit this response. Protein extracts from cells exposed to urea showed significant carbamylation that increased as a function of time. These results demonstrate: (1) that urea is neurotoxic in vitro and that creatinine is not: (2) that the insult urea causes is not simply the result of hypertonicity; but rather (3) that urea, via breakdown to cyanate and ammonium ions, may cause cell stress because of its ability to cause carbamylation of cellular proteins. The cells attenuation of the heat shock response after 10 h of exposure to urea suggests that they can adapt to the presence of urea or carbamylation. This may explain, in part, why the same degree of azotemia causes fewer neurological symptoms in patients with chronic as opposed to acute renal failure.
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PMID:Urea induces the heat shock response in human neuroblastoma cells. 878 97

Anandamide (arachidonoyl-ethanolamide, AnNH) and 2-arachidonoyl-glycerol (2-AG) have been suggested to act as endogenous agonists at the brain cannabinoid receptor, and their biosynthetic and degradative mechanisms in nervous tissues and cells have also been partially elucidated. Here we present evidence for the presence, in mouse N18TG2 neuroblastoma cells, of enzymatic activities potentially responsible for the biosynthesis of AnNH and 2-AG from a common phospholipid precursor. Cell homogenates were shown to catalyze: (a) the transfer of an arachidonoyl moiety from the sn-1 position of sn-1,2-di-arachidonoyl-phosphatidylcholine (AAPC) to phosphatidyl-ethanolamine (PE) to form N-arachidonoyl-PE (N-ArPE) and sn-1-lyso-2-arachidonoyl-PC (lyso-APC), (b) the hydrolysis of N-AtPE to AnNH, (c) the hydrolysis of lyso-APC to 2-AG, (d) the hydrolysis of AAPC to sn-1,2-di-arachidonoyl-glycerol (AAG), and (e) the hydrolysis of AAG to 2-AG. From these findings it is possible to suggest that AAPC may serve as precursor for both AnNH and 2-AG biosynthesis through three different pathways.
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PMID:Potential biosynthetic connections between the two cannabimimetic eicosanoids, anandamide and 2-arachidonoyl-glycerol, in mouse neuroblastoma cells. 885 37

Chitinase has been purified from the extract of cabbage stems with roots through successive steps of ammonium sulfate fractionation, Sephadex G-75 gel filtration, chromatofocusing and Sephacryl S-200 HR gel filtration. By these steps, the purity of the enzyme increased by 63 fold and the recovery of the enzyme activity was 18%. The purified enzyme was homogeneous when analyzed by SDS-PAGE. It showed an optimal pH of 6 and optimal temperature of 60 degrees C for hydrolysis of ethylene glycol chitin (EGC). The molecular mass of the enzyme was 41 kDa, as determined by SDS-PAGE. Heavy metal ions (1.5 mM) Ag+, Hg2+ and Fe2+, and chemical modification agents NAI (1 mM), NBS (0.5 mM) and CHD (0.5 mM) significantly or completely inhibited the activity of the enzyme. Substrate EGC at high concentrations also inhibited the activity. BSA (0.05%), Triton X-100 (0.5%) and glycerol (50%) provided significant protection of the enzyme from freezing inactivation.
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PMID:Purification and properties of chitinase from cabbage stems with roots. 889 65

Multiple cellular responses are regulated through the generation of lipid second messengers upon activation of phospholipases. One such response concerns the activity of a class of kinase constituting the protein kinase C family. The production of specific molecular species of lipid second messengers may be therefore of prime importance in the activation of a member of the PKC isoforms. Prompted by this possibility we investigated the production of 1,2 diacyl-sn-glycerol (DAG) and phosphatidic acid (PtdOH) in LA-N-1 neuroblastoma cells under various physiological states. 12-0-Tetradecanoylphorbol 13-acetate (TPA) stimulation activated a phospholipase D (PLD) specific for phosphatidylcholine (PtdCho) in proliferating cells and a phospholipase C (PLC) specific for phosphatidylethanolamine (PtdEtn) in retinoic acid (RA) differentiated cells. These separate activations produced different molecular species of DAG or PtdOH. PtdOH was able to stimulate the Ca2+ dependent protein kinase C (PKC) by a mechanism which differed from the action of DAG. PtdOH did not induce the translocation of the PKC to the membrane. Moreover PtdOH, in contrast to DAG, prevented PKC degradation by inhibiting the enzymatic hydrolysis by m-calpain. These observations suggest that the stimulation of cells by agonists elicited the production of specific molecular species of lipid second messengers depending on the physiological status of the cells, and probably on the nature of the stimulus. It seems therefore likely that the generation of specific lipid second messengers may activate specific PKC isoforms resulting in a specific cellular response.
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PMID:Production and function of lipid second messengers in proliferating and differentiated neuroblastoma cells. 890 81

In cultures of rat cerebral neurons addition of the protein kinase C (PKC) activator 1,2-dioctanoyl-s,n-glycerol (diC8; 5 microM) induces a transient elongation of filopodia which is followed by a striking enhancement of lamellar protrusions. After 30-40 min, lamellipodia are slowly retracted, filopodia reappear and become predominant again. The reappearance of filopodia is accelerated by addition of the potent PKC-inhibitor RO-31-8220 (2 microM). A similar transient promotion of lamellar protrusive activity is obtained in SH-SY5Y neuroblastoma cells upon stimulation by acetylcholine or diC8. Immunostainings showed that the new space created by extending actin-driven lamellipodia is rapidly entered by microtubules. Preincubation with or permanent presence of RO-31-8220 totally inhibits both filopodial and lamellipodial protrusive activity. The data suggest that both filopodial and lamellipodial protrusion require active PKC, however of different levels of activation.
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PMID:In growth cones of rat cerebral neurons and human neuroblastoma cells, activation of protein kinase C causes a shift from filopodial to lamellipodial actin dynamics. 897 8

The fundamental event in prion diseases involves a conformational change in one or more of the alpha-helices of the cellular prion protein (PrP(C)) as they are converted into beta-sheets during the formation of the pathogenic isoform (PrP(Sc)). Here, we show that exposure of scrapie-infected mouse neuroblastoma (ScN2a) cells to reagents known to stabilize proteins in their native conformation reduced the rate and extent of PrP(Sc) formation. Such reagents include the cellular osmolytes glycerol and trimethylamine N-oxide (TMAO) and the organic solvent dimethylsulfoxide (DMSO), which we refer to as 'chemical chaperones' because of their influence on protein folding. Although the chemical chaperones did not appear to affect the existing population of PrP(Sc) molecules in ScN2a cells, they did interfere with the formation of PrP(Sc) from newly synthesized PrP(C). We suggest that the chemical chaperones act to stabilize the alpha-helical conformation of PrP(C) and thereby prevent the protein from undergoing a conformational change to produce PrP(Sc). These observations provide further support for the idea that prions arise due to a change in protein conformation and reveal potential strategies for preventing PrP(Sc) formation.
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PMID:Chemical chaperones interfere with the formation of scrapie prion protein. 897 63

When SK-N-BE(2) human neuroblastoma cells were exposed for 1h to growth medium supplemented with [14C]arachidonic acid (AA) at final concentrations ranging from 1 microM to 100 microM, an amount of this fatty acid was uptaken ranging form a 2% to a 120% of that present in cells at steady state. As more [14C]AA was uptaken by cells, a larger fraction was progressively incorporated into triacylglycerols (TAG) in comparison to phospholipids (PL), with minor amounts remaining in a free form. By gas chromatographic analysis it was estimated that TAG from cells grown in ordinary medium contained about 2 nmoles AA per mg protein, but, after 1 h exposure to medium supplemented with 100 microM AA (label-free) this value rose to about 28 nmoles/mg protein; furthermore, as estimated on the basis of total fatty acid content, TAG mass was increased by a 16%. Cell exposure to medium enriched with 100 microM AA did not cause PL mass changes, whereas AA content was significantly increased only in phosphatidylcholine. Medium enrichment with 100 microM AA dramatically enhanced [3H]glycerol incorporation into TAG, as assessed after 1 h cell pulse, with minor but significant changes observed also for phosphatidylinositol and phosphatidylethanolamine, but not for phosphatidylcholine. In the light of these data, the contribution of PL and TAG to the removal of free intracellular AA is discussed.
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PMID:Different contribution of phospholipid and triacylglycerol metabolism to esterification of free intracellular arachidonate: a study on SK-N-BE(2) human neuroblastoma cells. 904 40

The growth rate of the human neuroblastoma LAN-1 cells was decreased half after 48 h of incubation with dialkylglycerophosphocholine 1-O-octadecyl 2-O-methyl-sn-glycero-3-phosphocholine (ET-18-O-CH3), at 4 microM. Four radiolabelled precursors, [3H]hexadecanol, [3H]hexadecanoic, [3H]arachidonic acids, or N-acetyl[14C] neuraminic acid were added in the culture medium to follow their cell incorporation among various glycerolipids, gangliosides and eicosanoids. Several modifications of the glycerophospholipid synthesis induced by ET-18-O-CH3 were observed. The inhibition of 1-O-[3H]hexadecanoyl 2-O-acyl glycerophosphocholine synthesis provoked the accumulation of diacylglycerophosphoethanolamine. The inhibition of 1-O-[3H]hexadecyl 2-O-acyl glycerophosphocholine and ethanolamine synthesis enhanced the synthesis of non phosphorous glycerolipids with 1-O-[3H]hexadecyl-sn-glycerol backbone. The eicosanoid synthesis was not disturbed. Alterations of ether- ester- and diester-linked glycerophospholipid and non phosphorous glycerolipid synthesis could modify the lipid membrane distribution and affect the enzymatic pathway of the ceramide synthesis. An excess of [3H]hexadecanoyl-amide molecular species of ceramides in mono- and disialo-gangliosides was observed. By contrast the N-acetyl [14C]neuraminosyl-linkage in these two groups of gangliosides never reached the hypersialylation process described during sialoglyco-peptide synthesis in murine carcinoma kidney cell lines. Both metabolic disturbances of the glycerolipid and ganglioside synthesis reported for the neuroblastoma LAN-1 cell line sensitive to ET-18-O-CH3 extend and confirm the previous studies with other more resistant cell lines from the murine Meth A sarcoma and the rat colon carcinoma.
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PMID:Severe modifications of ether- ester- or diester-linked glycerolipid and non glycerolipid synthesis in human neuroblastoma LAN-1 cells cultured with octadecylmethylglycerophosphocholine. 933 88

A substantial amount of lysophosphatidic acid (LPA) (15.66 nmol/g tissue) was found to occur in the brain isolated from rats killed in liquid nitrogen. We found that a significant portion of brain LPA was accounted for by the arachidonic acid-containing species (5.4%). We obtained evidence that both 2-arachidonoyl species and 1-arachidonoyl species of LPA are present. The occurrence of 2-arachidonoyl LPA in the brain (0.53 nmol/g tissue) is a notable observation, because of its structural resemblance to 2-arachidonoyl-sn-glycerol (2-AG), an endogenous cannabinoid receptor ligand. We then examined the biological activity of 2-arachidonoyl LPA and compared it with that of 2-AG using neuroblastoma x glioma hybrid NG108-15 cells which express both the LPA receptor and cannabinoid CB1 receptor. We found that 2-arachidonoyl LPA interacts with the LPA receptor(s) to elicit the elevation of intracellular free Ca(2+) concentrations, whereas 2-AG interacts exclusively with the cannabinoid CB1 receptor. Next, we examined the possible metabolic relationship between 2-arachidonoyl LPA and 2-AG and obtained clear evidence that rapid enzymatic conversion of 2-arachidonoyl LPA to 2-AG took place in the brain homogenate. It is noteworthy that two types of endogenous ligands, that interact with different types of receptors, are closely related metabolically and rapidly interconvert.
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PMID:2-Arachidonoyl-sn-glycero-3-phosphate, an arachidonic acid-containing lysophosphatidic acid: occurrence and rapid enzymatic conversion to 2-arachidonoyl-sn-glycerol, a cannabinoid receptor ligand, in rat brain. 1205 82

1-Methyl-4-phenylpyridinium (MPP+) is a mitochondrial Complex I inhibitor and is frequently used to investigate the pathological degeneration of neurons associated with Parkinson's disease (PD). In vitro, extracellular concentration of glucose is one of the most critical factors in establishing the vulnerability of neurons to MPP+ toxicity. While glucose is the primary energy fuel for the brain, central nervous system (CNS) neurons can also take up and utilize other metabolic intermediates for energy. In this study, we compared various monosaccharides, disaccharides, nutritive/non-nutritive sugar alcohols, glycolytic and gluconeogenic metabolic intermediates for their cytoprotection against MPP+ in murine brain neuroblastoma cells. Several monosaccharides were effective against MMP+ (500 microM) including glucose, fructose and mannose, which restored cell viability to 109 +/- 5%, 70 +/- 5%, 99 +/- 3% of live controls, respectively. Slight protective effects were observed in the presence of 3-phosphoglyceric acid and glucose-6-phosphate; however, no protective effects were exhibited by galactose, sucrose, sorbitol, mannitol, glycerol or various gluconeogenic and ketogenic amino acids. On the other hand, fructose 1,6 bisphosphate and gluconeogenic energy intermediates [pyruvic acid, malic acid and phospho(enol)pyruvate (PEP)] were neuroprotective against MPP+. The gluconeogenic intermediates elevated intracellular levels of ATP and reduced propidium iodide (PI) nucleic acid staining to live controls, but did not alter the MPP(+)-induced loss of mitochondrial O2 consumption. These data indicate that malic acid, pyruvic acid and PEP contribute to anaerobic substrate level phosphorylation. The use of hydrazine sulfate to impede gluconeogenesis through PEP carboxykinase (PEPCK) inhibition heightened the protective effects of energy substrates possibly due to attenuated ATP demands from pyruvate carboxylase (PC) activity and pyruvate mitochondrial transport. It was concluded from these studies that several metabolic intermediates are effective in fueling anaerobic glycolysis during mitochondrial inhibition by MPP+.
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PMID:The role of glycolysis and gluconeogenesis in the cytoprotection of neuroblastoma cells against 1-methyl 4-phenylpyridinium ion toxicity. 1256 89


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