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

Glutamine synthetase was found to be increased in C-6 glioma cells as a result of increasing culture passage and N-6,2'-O-dibutyryl cyclic AMP (dbcAMP) treatment. At low passage dbcAMP produced a 2.5-fold increase in glutamine synthetase activity per unit of cellular protein. At high passage control glutamine synthetase was approximately double that seen at low passage, but dbcAMP produced an additional 65% increase. Lactate dehydrogenase activity was also increased by dbcAMP treatment at both low and high passage, but culture passage produced no change in the lactate dehydrogenase. With increasing culture passage, the ratio of cellular protein to DNA doubled. Therefore, expression of data per unit of protein tended to minimize the apparent changes in activity. The maximum increase in glutamine synthetase activity produced by both dbcAMP and increasing culture passage and expressed on a DNA basis was 5.6-fold. The increase in glutamine synthetase activity was generally linear during the first 20 h of drug treatment, after which enzyme activity remained nearly constant up to 72 h. Ninety percent or more of the dbcAMP remained in the medium at the end of 48-h exposure of cells to dbcAMP. 8-br-Cyclic AMP also increased glutamine synthetase activity of C-6-cels, but n-butyrate did not. Isoproterenol, which increases cyclic AMP in C-6-cells, increased glutamine synthetase activity. The effect of isoproterenol on glutamine synthetase was inhibited by the beta-adrenergic blocking agent sotalol. Cycloheximide (10 micrograms/ml) inhibited the dbcAMP effect on glutamine synthetase activity and also decreased the control enzyme activity by 60%.
 ...
PMID:Induction of glutamine synthetase by dibutyryl cyclic AMP in C-6 glioma cells. 612 56

Enzyme induction by hydrocortisone (HC) and dibutyryl cyclic AMP (dbcAMP) was studied in C6 rat glioma cells, FU5AH rat hepatoma cells, and five C6 x FU5AH hybrids. Hormone responsive enzymes from both parental lines were studied, including: tyrosine aminotransferase (TAT), alanine aminotransferase (AAT), glycerol phosphate dehydrogenase (GPDH), lactate dehydrogenase (LDH), and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP). There was no overall dominance of one parental phenotype over the other in expression of uninduced or induced enzyme activity after fusion, and the hybrids possessed some enzymatic properties characteristic of both parents. GPDH was induced by dbcAMP in all five hybrids, and TAT was induced by dbcAMP in four of the hybrids, although neither of these enzymes were induced by dbcAMP in the parents. Furthermore, synergistic induction of these enzymes by HC and dbcAMP was observed in the hybrids but not in the parents. These hybrids provide a model system to study hormone interaction in enzyme induction.
 ...
PMID:Synergistic enzyme induction by glucocorticoids and cyclic AMP observed in glioma x hepatoma cell hybrids but not in their parents. 614 8

Acetylcholine metabolism has been studied in sister cultures of E13 rat spinal cord cells cultured for 1 to 3 weeks with or without conditioned medium (CM) from rat skeletal muscle cells. Spinal cord cells grown with CM synthesized and accumulated 3 to 4 times more [3H]ACh from [3H]choline than cultures grown without CM. This effect of CM was accompanied by a comparable increase in CAT activity and could not be mimicked by increasing the density of the spinal cord cultures. A 2- to 3-fold increase in AChE activity was also observed in 2- to 3-week-old CM cultures, whereas the activity of lactate dehydrogenase was identical in cultures grown with and without CM. We have compared the effects of CMs from various non-neuronal cell cultures on [3H]ACh synthesis and storage by spinal cord cultures and by sympathetic neuron cultures. CM by skeletal muscle greater than skin fibroblasts greater than rat heart muscle greater than C6 glioma cells were the most active on both types of neuron cultures, whereas CM from rat brain, L6 myoblasts, mouse 3T3, and PYT21 fibroblasts was inactive on spinal cord cultures and only weakly active on sympathetic neurons. Serum-free CM from skeletal muscle was inactive on both types of neuron cultures. The CM factor active on spinal cord cultures has been purified several thousand-fold by using a four-step fractionation scheme which has previously led to a partial purification of the CM factor involved in the regulation of CAT, AChE, and catecholamine-synthesizing enzymes in sympathetic neuron cultures ( Swerts , J. P., A. Le Van Thai, A. Vigny , and M. J. Weber (1983) Dev. Biol. 100: 1-11). Moreover, a comparison of dose-response curves established with this purified material showed that it exerted its effects on spinal cord and on sympathetic neuron cultures in the same range of concentration. Thus, these results suggest that the same macromolecule is involved in the regulation of neurotransmitter phenotype in both types of cultures despite their different embryological origins.
 ...
PMID:Acetylcholine metabolism in rat spinal cord cultures: regulation by a factor involved in the determination of the neurotransmitter phenotype of sympathetic neurons. 614 37

The mechanism of isoproterenol and N6,O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cAMP) induction of lactate dehydrogenase (EC 1.1.1.27) was investigated in the C6 rat glioma cell line. [3H]Leucine-labeled lactate dehydrogenase in noninduced and induced cells was quantitatively immunoprecipitated with rabbit anti-rat lactate dehydrogenase-5 antiserum. The immunoprecipitates were analyzed for 3H-labeled lactate dehydrogenase by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels and isoelectrofocusing. Using this technique, it was shown that isoproterenol + 3-isobutyl-1-methylxanthine and dibutyryl cAMP cause an increase of the [3H]leucine incorporation into glioma cell lactate dehydrogenase. Analysis of the kinetics of induction and deinduction revealed no change in the rate of degradation of lactate dehydrogenase in the presence and absence of inducing agent, indicating that the induction was due to an increase in the rate of synthesis of the enzyme. The increased rate of synthesis was prevented by actinomycin D. Isoproterenol + 3-isobutyl-1-methylxanthine increased only the specific rate of synthesis of lactate dehydrogenase-5 isozyme and of the M subunit. The mechanism was further studied by assaying the level of functional mRNA coding for lactate dehydrogenase in a reticulocyte cell-free protein-synthesizing system using glioma cell poly(A)-containing RNA isolated from either isoproterenol or dibutyryl cAMP-induced cells. Analysis of the immunoprecipitated translation product by isoelectrofocusing revealed that isoproterenol or dibutyryl cAMP produced an approximately 8-fold stimulation of the poly(A) + RNA-directed synthesis of the lactate dehydrogenase M subunit. These data demonstrate that isoproterenol and dibutyryl cAMP control the level of functionally active lactate dehydrogenase mRNA in glioma cells which, in turn, determines the extent of synthesis of the lactate dehydrogenase M subunit.
 ...
PMID:Cyclic AMP regulation of lactate dehydrogenase. Isoproterenol and N6,O2'-dibutyryl cyclic AMP increase the levels of lactate dehydrogenase-5 isozyme and its messenger RNA in rat C6 glioma cells. 616 Jan 45

The specific activity of lactate dehydrogenase (LDH; EC 1.1.1.27) is induced two-fold by l-norepinephrine (NE) in C6TK- rat glioma cells, but not in NA mouse neuroblastoma cells or various other nonglial cells. Previous reports have shown that the induction is mediated by cyclic AMP (cAMP) and possibly protein phosphorylation, and that it requires RNA and protein synthesis. To study the block to LDH induction in nonglial cells, we hybridized C6TK- cells with NA cells and isolated a hybrid clone in which LDH is inducible by NE. Mouse and rat LDH from hybrid cells were separated by electrophoresis and quantitated by two independent methods, and it was found that mouse and rat LDH were induced equally when cells were exposed to NE. The results suggest that inducibility of LDH is not determined by a cis-acting control at the gene level, but rather by the presence or absence of an earlier component in the cAMP-mediated induction system, and that the induction system acts indiscriminately on all active LDH gene copies in the cell.
 ...
PMID:Induction of both rat and mouse lactate dehydrogenase in hybrids between inducible rat glioma and uninducible mouse neuroblastoma cells. 625 3

We have cloned DNA complementary to mRNA coding for rat C6 glioma cell lactate dehydrogenase M-subunit. Double-stranded DNA complementary to a portion of lactate dehydrogenase mRNA was inserted into the Pst I site of plasmid pBR322 by the dC.dG tailing technique and amplified in Escherichia coli HB101. A recombinant plasmid containing lactate dehydrogenase cDNA was identified by colony hybridization to a cDNA prepared from partially purified lactate dehydrogenase mRNA and by hybridization-selected translation. The recombinant plasmid (pRLD42) contains a 680 nucleotide insert of lactate dehydrogenase mRNA. Hybridization of nick-translation pRLD42 to glioma cell poly(A)+RNA separated on agarose gel and transferred to nitrocellulose exhibited Mr = 5.9 X 10(5) for lactate dehydrogenase mRNA. Furthermore, Northern blot analysis of RNA from unstimulated and isoproterenol-stimulated glioma cells indicated a 2-fold increase of lactate dehydrogenase mRNA molecules in stimulated cells. The 2-fold increase of lactate dehydrogenase mRNA was confirmed by RNA-excess kinetic hybridization using pRLD42 DNA and poly(A)+RNA from unstimulated, isoproterenol-, and dibutyryl cAMP-stimulated glioma cells. These data demonstrate that isoproterenol and dibutyryl cAMP cause an increase of the number of lactate dehydrogenase M-subunit mRNA molecules in glioma cells which, in part, determines the extent of synthesis of the lactate dehydrogenase M-subunit.
 ...
PMID:Cyclic AMP regulation of lactate dehydrogenase. Quantitation of lactate dehydrogenase M-subunit messenger RNA in isoproterenol-and N6,O2'-dibutyryl cyclic AMP-stimulated rat C6 glioma cells by hybridization analysis using a cloned cDNA probe. 627 88

The concentration of glycerol-3-phosphate dehydrogenase (GPDH; sn-glycerol-3-phosphate:NAD(+) 2-oxidoreductase, EC 1.1.1.8) had previously been determined to be regulated by glucocorticoids in rat brain cells in vivo and in cell culture. We now demonstrate that concanavalin A (Con A) can inhibit the induction of GPDH in dose-dependent manner in C6 rat glioma cells and in primary cultures of rat brain oligodendrocytes. Con A is not cytotoxic, because its effect can be prevented or reversed by alpha-methyl mannoside. The inhibition specifically prevents the appearance of new molecules of GPDH, although Con A does not significantly inhibit protein synthesis in these cells, nor does it affect the activity of another soluble enzyme, lactate dehydrogenase. The ability to block enzyme induction is not limited to Con A, because other lectins also inhibit induction, with Ricinus communis agglutinin 60 being the most potent (50% inhibition of induction at 0.0083 muM) and wheat germ agglutinin being the least potent (50% inhibition of induction at 1.2 muM). The molecular mechanism by which Con A inhibits GPDH induction appears to be by the "down regulation" of the cytoplasmic glucocorticoid receptors, because exposure to Con A results in the loss of more than 90% of the receptor activity. Con A does not inhibit the receptor assay and no direct interaction between the receptor and Con A could be demonstrated. This down regulation is not tumor cell specific and appears to be a general phenomenon, because it occurs in normal oligodendrocytes and even in normal astrocytes (a cell type in which the gene for GPDH is not expressed). The down regulation of glucocorticoid receptors in normal brain cells suggests two important corollaries. First, it demonstrates the existence of a rate-limiting step controlling the glucocorticoid-dependent gene expression in brain cells and possibly represents a regulatory site common to all glucocorticoid target cells. Second, it suggests that the response to glucocorticoids of oligodendrocytes and astrocytes can be regulated in vivo by cell surface contact with endogenous lectins, neighboring cells, or both.
 ...
PMID:Cell surface modulation of gene expression in brain cells by down regulation of glucocorticoid receptors. 694 Jan 41

To provide the significance of LDH isozymes in rat CNS tumors, the changes in lactic dehydrogenase isozyme and calculated ratios of H- to M- subunit were studied by means of polyacrylamide gel enzymoelectrophoresis in tumor extracts from CNS tumors (7 astrocytomas, 4 oligodendrogliomas, 7 mixed gliomas, 6 anaplastic gliomas, 3 glioependymomas, 1 astroblastoma, 11 neurinomas, 8 anaplastic neurinomas and 1 meningioma in Wistar rats which were induced by ethylnitrosourea). The isozyme patterns were compared to those obtained from normal rat CNS tissues. Among the glioma group, oligodendroglioma showed the highest H/M ratio followed by mixed glioma, glioependymoma, astrocytoma, astroblastoma and anaplastic glioma in order of decreasing of H/M ratios. On the other hand, the H/M ratio of neurinoma was significantly higher than that of anaplastic neurinoma. These observation suggested that determination of LDH isozyme patterns could supplement the histological evaluation of brain tumors.
 ...
PMID:LDH isozyme analyses of ethylnitrosourea-induced central nervous system tumors in rats. 739 14

We examined whether oligodendrocytes, neurons, and astroglia derived from the human central nervous system differ in susceptibility to injury mediated by tumor necrosis factor (TNF)-alpha and by activated CD4+ T cells acting via a TNF-independent mechanism. Injury was assessed either as cell membrane-directed (lysis), measured by 51chromium (Cr) or lactate dehydrogenase (LDH) release, or nucleus-directed (apoptosis), measured by morphologic features based on propidium iodide (PI) staining and by DNA fragmentation measured by a terminal transferase (TdT)-mediated dUTP biotin nick end labeling technique (TUNEL). TNF did not induce 51Cr or LDH release in any cell targets, but did induce nuclear (66 +/- 2% of cells) and DNA (68 +/- 2% of cells) fragmentation selectively in the oligodendrocytes over 96 hr. At this time, there was no significant loss of oligodendrocyte cell number. Nuclear injury could be induced in neurons by serum deprivation and in malignant astrocytes by the combination of TNF and low serum. CD4+ T cells activated with phytohemagglutin (pha) or anti-CD3 plus interleukin-2 induced significant 51Cr and LDH release in all target cells tested; only pha-activated CD4+ T-cell cocultures showed reduced target cell numbers. Significant nuclear fragmentation was observed only for glioma cells (22 +/- 1% of cells). Differences in susceptibility to different immune effector mechanisms and in the nature of the injury response to the same effector mediator among human CNS-derived neural cells will need to be considered in design of therapeutic strategies aimed at protecting or limiting target cell injury consequent to disease or trauma.
 ...
PMID:Differential susceptibility of human CNS-derived cell populations to TNF-dependent and independent immune-mediated injury. 747 83

In the present study the effect of cocaine on thymidine, uridine and leucine incorporation was assessed in primary cortical glial and C6 glioma cells. Cocaine exposure for 24 h inhibited thymidine and uridine incorporation in cortical glial and C6 glioma cells. However, the effect of cocaine on uridine incorporation was less prominent compared to thymidine incorporation. High concentrations of cocaine inhibited leucine incorporation in C6 glioma cells but not in cortical glia. Cocaine exposure for four days decreased cell proliferation of cortical glial and C6 glioma cells. Cocaine-induced attenuation of macromolecular syntheses was not due to cell death since cocaine-treated cells were not stained with Trypan Blue and did not release lactate dehydrogenase into culture supernatants. Furthermore, cocaine had no effect on glutamate uptake either in cortical glia or in C6 glioma cells. These results indicate that cocaine inhibits macromolecular syntheses in glial cells. The inhibition of macromolecular syntheses in glial cells may be the mechanism involved in cocaine-induced fetal brain growth retardation.
 ...
PMID:Effect of cocaine on macromolecular syntheses and cell proliferation in cultured glial cells. 750 70


<< Previous 1 2 3 4 5 6 7 8 9 Next >>