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)

The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor.
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PMID:Observations of energy metabolism in neuroectodermal tumors using in vivo 31P-NMR. 403 75

Specific, GTP hydrolysis catalyzed by membranes prepared from neuroblastoma--glioma (NG108-15) hybrid cells can be measured in the presence of adenosine-5'-[beta, gamma-imido] triphosphate (p[NH]ppA), ATP, and a nucleotide triphosphate-regenerating system. Opiates and opioid peptides stimulate low Km GTP hydrolysis when measured in the presence of Na+ and Mg2+. Opiate stimulation is rapid, stereospecific, and reserved by the antagonist naloxone. Potencies of opiates as stimulators of GTP hydrolysis and as inhibitors of adenylate cyclase are closely correlated. Agents that stimulate adenylate cyclase, including prostaglandin E1, 2-Cl-adenosine, secretin, and NaF, have little or no effect upon the rate of GTP hydrolysis. Opiates have no effect upon either adenylate cyclase or GTPase activity in membranes prepared from C6-BU1 glioma cells, which lack opiate receptors. In view of the pivotal role of GTP in the activation of adenylate cyclase, we conclude that receptor-mediated stimulation of GTP hydrolysis is the mechanism by which opiates and other inhibitory hormones lower adenylate cyclase activity in NG108-15 cell membranes.
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PMID:Opiates inhibit adenylate cyclase by stimulating GTP hydrolysis. 611 72

The reappearance of beta-adrenergic receptors in C6-glioma cells after desensitization with isoproterenol was studied using the antagonist [3H]CGP-12177. Reappearance had the following properties: (a) it occurred in intact cells only, (b) it was temperature dependent, (c) it required an Na+/H+ gradient, low intracellular Ca2+ activity, and (d) it required ATP, and (e) intact lysosomes. The results suggest endocytosis and recycling of the beta-adrenergic receptor after agonist treatment.
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PMID:Reappearance of beta-adrenergic receptors after isoproterenol treatment in intact C6-cells. 613 60

Clonidine and several analogues of clonidine are shown to be useful probes for alpha 2-adrenergic receptors in a comparative study of ligand binding and inhibition of adenylate cyclase. The alpha-adrenergic properties of a new potential probe, N-(4-hydroxyphenacetyl)-4-aminoclonidine hydrochloride, are described. [3H]Clonidine binds to alpha-receptors of NG108-15 neuroblastoma X glioma hybrid cell membranes with Kd values of 1.7 and 33 nM for putative high-affinity and low-affinity sites, respectively. p-Aminoclonidine and hydroxyphenacetyl aminoclonidine displace [3H]clonidine from the high-affinity sites with Kd values of 2.3 and 5.8 nM, respectively. Rat brain alpha 2-receptors also exhibit high affinity toward clonidine, p-aminoclonidine, and hydroxyphenacetyl aminoclonidine, as determined by displacement of specifically bound [3H]clonidine. Clonidine, p-amino-clonidine, and hydroxyphenacetyl aminoclonidine elicit modest inhibition (up to 24%) of NG108-125 adenylate cyclase by interaction with alpha 2-receptors (Kd,app 300, 30, and 130 nM, respectively); these compounds also partially reverse the inhibition elicited by (--)-norepinephrine. Components of the adenylate cyclase assay mixture, particularly ATP, GTP, sodium ions, and a nucleoside-triphosphate-regenerating system, decrease the high-affinity [3H]clonidine binding to NG108-15 membranes; in the presence of these components, alpha-receptors possess only low affinity (Kd 43 nM) for [3H]clonidine. The results are consistent with the concept that certain components required for the receptor-mediated inhibition of adenylate cyclase convert alpha 2-receptors from a high-affinity inactive state to a low-affinity active state.
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PMID:Interaction of clonidine and clonidine analogues with alpha-adrenergic receptors of neuroblastoma X glioma hybrid cells and rat brain: comparison of ligand binding with inhibition of adenylate cyclase. 626 Apr 85

A doubly transformed rat glioma cell line, designated C6V-1, was obtained from rat glioma C6 cells by infection with a rat-adapted variant of Moloney sarcoma virus (MSV-M-os). The C6V-1 cells show karyotypic changes in chromosome number (43) and structure, while C6 cells possess a normal male karyotype. C6V-1 and C6 cells were employed for characterization of a receptor-adenylate cyclase system of the surface membrane. C6V-1 cells showed lower adenylate cyclase activity than that of C6 cells, though the apparent Km for ATP in both types of cells was the same. The maximal stimulation of adenylate cyclase by isoproterenol was significantly reduced, and Kact for isoproterenol was approximately 18-fold lower in C6V-1 cells. When the concentration of beta-adrenergic receptors was measured by various concentrations of [3H] dihydroalprenolol (DHA), the maximal binding sites of C6 and C6V-1 cells were 760 and 230 fmol/mg protein, respectively, without any changes in the association constant for DHA. The concentration of isoproterenol required for 50% displacement of the [3H] DHA binding (Kd) was the same (around 1.5 X 10(-6)M) in both cells, measured in the presence of GTP. Thus the 19-fold drop in the Kd/Kact ratio in C6V-1 cells suggests an incomplete coupling of beta-receptors to adenylate cyclase. Cyclic AMP phosphodiesterase activity and cAMP content in C6V-1 were lower than in C6 cells. Mitochondrial monoamine oxidase and cytosomal enolase activities, however, were somewhat higher in C6V-1 cells. The results indicate that a set of changes in the receptors and in the cyclic AMP system of C6V-1 is one of the specific alterations by transformation, even though those may not be the cause of cell transformation.
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PMID:Receptor-associated changes of the catecholamine-sensitive adenylate cyclase in glioma cells doubly transformed with Moloney sarcoma virus. 627 81

Three clones of neuroblastoma-glioma cells that contain low amounts of calmodulin were selected from the NG108-15 cells after several treatments with high concentrations of chlorpromazine. Purified membranes of the three clones had decreased numbers of both alpha-adrenergic and opiate receptors, monitored with [3H]yohimbine and [3H,D-Ala2]methionine encephalinamide, respectively. No changes were observed in the affinity of these radioactive ligands to the receptors of the selected cells as compared to the parent cells. Addition of bovine brain calmodulin did not affect the binding of [3H,D-Ala2]methionine encephalinamide to the membranes of the selected cells and they had the same number of acetylcholine receptors, determined with 1-quinuclidinyl-[phenyl-4-3H]-benzilate, as the parent NG108-15 cells. The basal ATPase activity in the membranes of the selected cells was 35-50% of the parent cells, with a decreased V value and no significant change in the affinity constant Ka to ATP. Addition of Ca2+ to the purified membranes increased the V of the ATPase in the selected as well as the parent cells but the V of the selected cells remained lower than that of the parent cells. Ca2+ had no effect on the Ka to ATP in either cell type. The Ca2+-dependent ATPase activity of both the parent and the selected cells was also calmodulin-dependent dependent since it was blocked in vitro by chlorpromazine. The co-regulation of opiate and adrenergic receptors and their interaction with calmodulin and Ca2+-ATPase is discussed in view of recent observations indicating biochemical and physiological association between opiates, Ca2+ and adrenergic compounds.
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PMID:A genetic approach to reveal the action of the opiate receptor in selected neuroblastoma-glioma cells. Interaction with alpha-adrenoceptors, calmodulin and Ca2+-ATPase. 629 58

The incorporation of methionine, lysine, and leucine into protein was studied in Ca2+-depleted and Ca2+-restored preparations of C-6 glial tumor cells in minimal medium. Although incorporation proceeded at linear rates in both preparations for more than 1 h and into the same spectrum of proteins, Ca2+-restored cells incorporated amino acid 5- to 10-fold more rapidly than Ca2+-depleted cells. Addition of approximately 200 microM Ca2+ in excess of chelator was required to achieve maximal rates of incorporation in Ca2+-depleted preparations. Stimulation by Ca2+ was rapid in onset (several minutes) and slowly reversible by chelator. Ca2+ was uniquely potent and specific among physiologically occurring cations in conferring such stimulation. Stimulation of amino acid incorporation by Ca2+ occurred over a broad range of pH and osmolarities and was facilitated by Mg2+. The effects of Ca2+ in stimulating amino acid incorporation were not traceable to changes in cAMP metabolism, amino acid uptake, protein catabolism, cell ATP or GTP content, or aminoacylation of transfer RNA. Actinomycin D (1 microgram/ml) did not block the stimulatory effects of Ca2+ although puromycin and cycloheximide did. The stimulatory effects of Ca2+ on protein synthesis were not restricted to C-6 in minimal medium. Protein synthesis was reduced by ethylene glycol bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid 40 to 75% in C-6 glioma, GH3 pituitary tumor, PC-12 adrenal tumor, N2A neuroblastoma, and HeLa cells incubated under simulated growth conditions with various enriched media and sera. Ca2+-depleted S49 lymphoma, CHO ovarian tumor, and normal, dispersed chicken embryo cells in enriched medium responded to Ca2+ restoration with increased rates of protein synthesis as did collagenase-dispersed normal rat liver cells in minimal medium. Protein synthesis in rabbit reticulocyte lysates was also inhibited by Ca2+-selective chelators or by Ca2+ removal by parvalbumin affinity chromatography and the inhibition was reversed by Ca2+. These findings are consistent with the existence of a Ca2+ requirement in the translational phase of protein synthesis in eukaryotic cells.
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PMID:Identification of a Ca2+ requirement for protein synthesis in eukaryotic cells. 631 27

The metabolism of Ca2+ was studied in a neuronal model system, the clonal mouse neuroblastoma x rat glioma hybrid cell line 108CC5. 1. Homogenates of the hybrid cells exhibit a specific activity of Ca2+-ATPase considerably higher than that of homogenates of the parental cells. 2. Uptake and release of 45Ca2+ by the hybrid cells display two and three distinct phases, respectively, and indicate that 40--50% of the cell-associated Ca2+ is located at the cell surface. 3. The influx of 45Ca2+ is insignificantly affected by Mg2+ or Na+, slightly diminished by Ba2+ or Sr2+, strongly inhibited by La3+, Co2+ or prenylamine, and considerably enhanced by high (i.e., depolarizing) concentrations of K+. The efflux of 45Ca2+ is reduced by La3+. 4. The hybrid cells tend to maintain Ca2+ homeostasis with an overall cellular Ca2+ concentration of 0.5--0.7 mM. At 1.8 mM Ca2+ in the medium this implies the necessity of an extrusion pump in the plasma membrane. 5. A reduction in the hybrid cells of the level of ATP is paralleled by a decline in the content of Ca2+. This can only be explained by the existence of energy-dependent intracellular Ca2+ stores that effectively compete for Ca2+ with a Ca2+ pump located in the plasma membrane. The internal stores are not identical with the mitochondria because mitochondrial inhibitors hardly change Ca2+ metabolism. 6. Micromolar concentrations of the ionophore A23187 can switch off the internal Ca2+ stores without affecting considerably the influx of Ca2+ through the plasma membrane. 7. With switched-off Ca2+ stores it is possible to increase the cellular Ca2+ content distinctly and to bring it back again to the control values in an ATP-dependent manner, i.e. to demonstrate the action of a Ca2+-extrusion pump in the plasma membrane. 8. Under some conditions active extrusion of Ca2+ depends not only on ATP but also on the presence of extracellular Na+. 9. Similar results as with hybrid cells are also obtained with rat glioma cells. The methodology of combining energy deprivation with the application of the ionophore A23187 is possibly generally applicable to obtain insight into the Ca2+ metabolism of various cell types.
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PMID:Uptake and energy-dependent extrusion of calcium in neural cells in culture. 644 79

Methylmercury was taken up preferentially by mouse glioma and mouse neuroblastoma cells relative to inorganic mercury. Methylmercury uptake was depressed by lowering the cellular ATP level or the incubation temperature, while the uptake of inorganic mercury was not affected by these treatments. When the cells were treated with reagents such as cytochalasin B, colchicine and vinblastine which are known to affect membrane permeability, changes in permeability to methylmercury caused by these reagents were markedly different from those to inorganic mercury. Inorganic mercury above 2 x 10(-5)M caused the release of 2-deoxyglucose trapped in the cells and the amount of inorganic mercury taken up by the cells increased markedly at higher concentrations. Inorganic mercury thus appeared to move into the cells after disrupting the membrane barrier, while methylmercury can penetrate the cells without any noticeable damage to the barrier.
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PMID:Uptake of methylmercury and inorganic mercury by mouse glioma and mouse neuroblastoma cells. 689 18

High molecular weight polypeptides (HMWPs) of 270,000 to 340,000 were found to be major components of intermediate filaments prepared by Triton X-100 extraction after spreading of rat glioma C6, HeLa, Chinese hamster ovary, and simian virus 40-transformed Chinese hamster lung cells. C6 HMWPs were shown to resemble high molecular weight microtubule-associated proteins from hog brain by four criteria: (i) comigration in electrophoresis on high-resolution sodium dodecyl sulfate/polyacrylamide gels, (ii) one-dimensional peptide mapping, (iii) phosphorylation in vitro with [gamma-32P]ATP, and (iv) ability to promote microtubule assembly in vitro. HMWPs were also found to be major components of one-time polymerized C6 microtubule preparations, which contained a sizable amount of intermediate filaments. The predominant part of HMWPs present in these microtubule preparations was found not to copurify with microtubules in cycles of temperature-dependent assembly/disassembly but to remain with the cold-insoluble intermediate filaments. These results provide an explanation for the low yields that have hampered attempts to purify microtubule-associated porteins, in particular HMWPs, from cultured cells in the past. Moreover, they suggest that HMWPs might have a dual role in the cell, serving not only as regulators of microtubule assembly but also as linker components between microtubules and intermediate filaments.
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PMID:High molecular weight polypeptides (270,000-340,000) from cultured cells are related to hog brain microtubule-associated proteins but copurify with intermediate filaments. 693 30


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