Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysophosphatidic acid (LPA) functions as an extracellular lipid mediator stimulating phospholipase C and affecting the structure of the cytoskeleton in several cell types. In rat glioma C6 cells, LPA mobilizes calcium from intracellular calcium stores and reverts morphological changes induced by elevated cytosolic cAMP-concentrations. Here we show that LPA-stimulation of C6 cells loaded with the calcium-sensitive fluorescent dye indo-1 results in calcium release from a subset of intracellular calcium stores that are not sensitive to the tumor promoter thapsigargin and do not overlap with calcium stores depleted during purinergic receptor stimulation with ATP. Furthermore, depletion of LPA-sensitive calcium stores does not induce capacitative calcium entry from the extracellular space into the cytosol to the same extent as ATP. These results indicate that inositol phosphate signaling induced by LPA or ATP may differ in kinetics or in spatial organisation within the cell. This may represent a possible explanation for the previous observation that only LPA, but not other calcium-mobilizing agonists, reverts cAMP-induced changes in the cytoskeletal organization in C6 cells.
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PMID:Lysophosphatidic acid depletes intracellular calcium stores different from those mediating capacitative calcium entry in C6 rat glioma cells. 898 69

We examined the changes in phospholipid metabolisms in sodium butyrate-treated C6 glioma cells. Treatment of 2.5 mM sodium butyrate for 24 h induced an increase in the activity of glutamine synthetase, suggesting that these cells were under differentiation. Similar treatment was associated with (i) increased arachidonic acid incorporation into phosphatidylcholine, and (ii) decreased arachidonic acid incorporation into phosphatidylinositol and (iii) phosphatidylethanolamine. These effects were subsequently investigated by examining the acylation process, de novo biosynthesis, and the agonist-stimulated phosphoinositides hydrolysis in these cells. Our results indicated that sodium butyrate stimulated the acylation of arachidonic acid into lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylinositol. The glycerol incorporation into these lipids was not affected, but the inositol incorporation into total chloroform extracts and Pl and phosphatidylinositol 4-phosphate was decreased in the sodium butyrate-treated cells. Moreover, the accumulation of the rapid histamine-stimulated phosphoinositide metabolites, i.e., inositol monophosphate, inositol diphosphate, and inositol triphosphate (IP3) was decreased in these cells. To elucidate whether the decreased inositol phosphates were due to a decrease in the phosphoinositides hydrolysis, we measured the transient IP3 production directly by a receptor-binding assay. Our results indicated that histamine-stimulated transient IP3 formations were decreased. Taken together, these results indicated that multiple changes by multiple mechanisms of phospholipid metabolisms were found in sodium butyrate-treated C6 glioma cells. The decreased IP3 formation and its subsequent action, i.e., Ca2+ mobilization, may play an early but pivotal role by which sodium butyrate induces C6 glioma cell differentiation.
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PMID:Altered phospholipid metabolism in sodium butyrate-induced differentiation of C6 glioma cells. 907 64

Brain tissue cells have been shown to use two predominant pathways for energy production. The first of these is the pentose phosphate shunt, and the second is glycolysis, followed by the TCA cycle. Inhibition of these pathways can result in a reduction of ATP, and changes in the concentration of various metabolites. In the present study, the acute and chronic effect of 6-aminonicotinamide (6-AN) (0.01, 0.02, and 0.03 mg/ml) was examined on astrocytes and C6-glioma cells. Following this treatment, glucose, lactate, glutamate, ATP, and PCr were assayed according to the procedures of Lowry and Passonneau. Our data indicated that following 15 minutes treatment of astrocytes and C6-glioma with 6AN there was no significant difference in the concentration of metabolites measured. However, following 24 hours treatment there was a significant increase in glucose concentration and significant reduction in the concentration of ATP, PCr, lactate and glutamate in both cell types. Morphological changes appeared later following 48 hours treatment with 6-AN in both cell types. Glucose accumulation can be explained by the fact that it is the precursor to both glycolysis and the pentose phosphate shunt. If these processes are inhibited, glucose will obviously accumulate and products like ATP, PCr, lactate and glutamate will decrease. Additionally, there was significant differences in concentration of glucose and lactate between astrocytes and C6-glioma cells. The significance of these differences has been discussed.
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PMID:Effect of 6-aminonicotinamide on metabolism of astrocytes and C6-glioma cells. 910 36

1. Four different phospholipase C (PLC)-activating P2Y receptors have been cloned and stably expressed in 1321N1 human astrocytoma cells. These include the human homologues of the P2Y1, P2Y2 and P2Y4 receptors and the rat homologue of the P2Y6 receptor. 2. The nucleotide selectivities of these four receptors have been compared directly by measuring inositol phosphate accumulation in response to nucleotides under conditions in which the initial purity and stability of agonist was rigidly assured and quantitatively assessed. 3. The P2Y1 receptor is specific for adenine nucleotides and slightly more sensitive to disphosphates than triphosphates. When expressed in 1321N1 astrocytoma cells, it couples selectively to the stimulation of PLC and not to the inhibition of adenylyl cyclase. 4. The P2Y2 receptor is activated by UTP and ATP with similar potency and is not activated by nucleoside diphosphates. Diadenosine terraphosphate is a potent agonist at this receptor. 5. The P2Y4 receptor is highly selective for UTP over ATP and is not activated by nucleoside disphosphates. 6. The P2Y6 receptor is activated most potently by UDP, but weakly or not at all by UTP, ADP and ATP. The P2Y6 receptor appears to be identical to the uridine nucleotide-specific receptor previously characterized in C6-2B rat glioma cells. 7. We have identified a P2Y receptor on C6 glioma cells that inhibits adenylyl cyclase but has no effect on PLC. This receptor exhibits a pharmacological selectivity similar but not identical to that of the P2Y1 receptor. When the P2Y1 receptor was expressed in these C6 cells, it conferred an inositol lipid signalling response to adenine nucleotides that was pharmacologically identical to that of the P2Y1 receptor. Thus, the P2Y receptor of C6 glioma cells represents an additional receptor that exhibits the classical pharmacological selectivity of a P2Y1-R, but which couples to adenylyl cyclase rather than to PLC.
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PMID:Pharmacological and second messenger signalling selectivities of cloned P2Y receptors. 913 7

The relationship between the bioenergetic status of human glioma xenografts in nude mice and morphometric parameters of the perfused vascular architecture was studied using (31)P magnetic resonance spectroscopy (MRS), fluorescence microscopy and two-dimensional digital image analysis. Two tumour lines with a different vascular architecture were used for this study. Intervascular distances and non-perfused area fractions varied greatly between tumours of the same line and tumours of different lines. The inorganic phosphate-nucleoside triphosphate (P(i)/NTP) ratio increased rapidly as mean intervascular distances increased from 100 microm to 300 microm. Two morphometric parameters - the percentage of intervascular distances larger than 200 microm (ivd200) and the non-perfused area fraction at a distance larger than 100 microm from a nearest perfused vessel (area100), - were deduced from these experiments and related to the P(i)/NTP ratio of the whole tumour. It is assumed that an aerobic to anaerobic transition influences the bioenergetic status, i.e. the P(i)/NTP ratio increased linearly with the percentage of ivd200 and the area100.
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PMID:In vivo (31)P magnetic resonance spectroscopy and morphometric analysis of the perfused vascular architecture of human glioma xenografts in nude mice. 916 34

A perifusion technique for microscopy with computerized detection of early changes in cell morphology during continuous perifusion was used to show that the geometry of cultured glioma cells (MG-251) changes rapidly when they are exposed to estramustine phosphate (EMP). When the cells were exposed to 20 or 40 mg l(-1) EMP, cell volume projected cell area (PCA) rapidly increased. When the Na+,K+-ATPase blocker ouabain (100 micromol l(-1)) was added to the EMP (40 mg l(-1)) perifusion, the acute EMP response was eradicated. When the PCA curve for ouabain alone was subtracted from the curve of combined ouabain and EMP perifusion, the resulting curve showed that ouabain completely blocked the EMP-induced increase in PCA. When the Na+, K+, Cl- co-transport inhibitors bumetanide (10 micromol l(-1)), or furosemide (100 micromol l(-1)), were added to EMP (40 mg l(-1)), the acute increase in PCA seen for EMP alone was also completely blocked. This study shows that inhibitors of ion transmembrane transport can modify EMP-induced cell volume increases. This may be of particular importance since the blockers have been found to interfere also with the cytotoxic function of EMP during cell culture. Thus, it is possible that cell volume changes could serve as a rapid technique for predicting the cytotoxic activity of antineoplastic drugs.
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PMID:Computerized detection of morphological changes to glioma cells during estramustine and ion-channel blocker perifusion. 925 98

1. The rat homologue of the P2Y1 receptor has been heterologously expressed in 1321N1 human astrocytoma cells and in C6 rat glioma cells. 2. As has been shown previously for the turkey and human P2Y1 receptors, the rat P2Y1 receptor expressed in either cell type responded to 2MeSATP with increases in inositol phosphate accumulation that were competitively blocked by the antagonist PPADS. Neither of the wild type cell lines exhibited inositol phosphate responses to P2Y1 receptor agonists. 3. Expression of the rat P2Y1 receptor did not confer a capacity of 2MeSATP to inhibit adenylyl cyclase activity in 1321N1 cells. Moreover, the inhibition of adenylyl cyclase mediated by an endogenous P2Y receptor of C6 glioma cells was not enhanced by expression of the rat P2Y1 receptor. The P2Y receptor-mediated inhibition of adenylyl cyclase in C6 glioma cells expressing both the endogenous P2Y receptor and the rat P2Y1 receptor remained unaffected by PPADS. 4. Since the P2Y receptor responsible for inhibition of adenylyl cyclase in C6 glioma cells does not share the pharmacological or functional properties of the P2Y1 receptor, even when both receptors originate from the same species and are simultaneously expressed in the same cell line, it is concluded that the P2Y1 receptor is distinct from an endogenous P2Y receptor in C6 cells that couples to inhibition of adenylyl cyclase.
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PMID:Fidelity in functional coupling of the rat P2Y1 receptor to phospholipase C. 940 64

It has been found that sphingosine and sphingosylphosphorylcholine (amphiphilic cations) have a stimulatory, and cholesterol 3-sulfate (an amphiphilic anion), an inhibitory, effect on [14C]serine incorporation into phosphatidylserine in glioma C6 and rat liver microsomes. In glioma intact cells sphingosine stimulates phosphatidylserine synthesis in a process independent of protein kinase C, but suppressed by thapsigargin. We suggest that the stimulation of the enzyme occurs by the interaction of amphiphilic cations with the membrane cosubstrate phospholipids, leading to a charge redistribution on their phosphate groups, and hence facilitating the enzyme action. A new hypothesis concerning the mechanism of the serine base exchange reaction is discussed.
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PMID:Serine base exchange enzyme activity is modulated by sphingosine and other amphiphilic compounds: possible role of positive charge in increasing the synthesis of phosphatidylserine. 940 36

Dolichyl phosphate, an essential carrier lipid in the biosynthesis of N-linked glycoprotein, has been found to induce apoptosis in rat glioma C6 cells and human monoblastic leukemia U937 cells. In the present study, dolichyl phosphate and structurally related compounds were examined regarding their apoptosis-inducing activities in U937 cells. Dihydroheptaprenyl and dihydrodecaprenyl phosphates, of which isoprene units are shorter than that of dolichyl phosphate, induced apoptosis in U937 cells. This phenomenon occurred in a dose- and time-dependent manner, as seen with dolichyl phosphate-induced apoptosis. Derivatives of the same isoprene units of dolichyl phosphate, such as dolichol, dolichal or dolichoic acid, did not induce DNA fragmentation. Farnesyl phosphate and geranylgeranyl phosphate also failed to induce apoptosis. During apoptosis, the caspase family of cysteine proteases play important roles. We observed that apoptosis induced by dihydroprenyl phosphate was mediated by caspase-3-like (CPP32-like) activation but not by caspase-1-like (ICE-like) activation. This caspase-3-like activation was inhibited by a specific inhibitor of caspase-3, DEVD-CHO, but not by an caspase-1 inhibitor YVAD-CHO. We interpret these results to mean that dihydroprenyl phosphates with more than seven isoprene units have apoptosis-inducing activity and that their signal is mediated by caspase-3-like activation.
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PMID:Dihydroheptaprenyl and dihydrodecaprenyl monophosphates induce apoptosis mediated by activation of caspase-3-like protease. 946 Dec 54

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) generated in the stereoselective deamination of D-amino acids catalyzed by D-amino acid oxidase (DAAO). H2O2 readily crosses cellular membranes and damages DNA, proteins, and lipids. The scarcity of DAAO substrates in mammalian organisms and its co-localization with catalase in the peroxisomal matrix suggested that the cytotoxicity of ROS could be harnessed by administration of D-amino acids to tumor cells ectopically expressing DAAO in the cytoplasm. To evaluate this hypothesis, the cDNA encoding the highly active DAAO from the red yeast Rhodotorula gracilis was mutated to remove the carboxy-terminal peroxisomal targeting sequence. A clonal line of 9L glioma cells stably transfected with this construct (9Ldaao17) was found to synthesize active R. gracilis DAAO. Exposure of 9Ldaao17 cells to D-alanine resulted in cytotoxicity at concentrations that were nontoxic to parental 9L cells. Depletion of cellular glutathione further sensitized 9Ldaao17 cells to D-alanine (D-Ala). This result, combined with stimulation of pentose phosphate pathway activity and the production of extracellular H2O2 by 9Ldaao17 cells incubated with D-alanine implicates oxidative stress as the mediator of cytotoxicity. These results demonstrate that expression of R. gracilis DAAO in tumor cells confers chemosensitivity to D-alanine that could be exploited as a novel cancer gene therapy paradigm.
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PMID:Induction of cytotoxic oxidative stress by D-alanine in brain tumor cells expressing Rhodotorula gracilis D-amino acid oxidase: a cancer gene therapy strategy. 947 75


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