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)

Reactions mediated by the opiate receptors that inhibit adenylate cyclase (EC 4.6.1.1) are closely coupled to subsequent reactions that gradually increase adenylate cyclase activity of neuroblastoma X glioma NG108-15 hybrid cells. Opiate-treated cells have higher basal-, prostaglandin E1-, and 2-chloroadenosine-stimulated activities than do control cells. However, NaF or guanosine 5'-(beta, gamma-imido)triphosphate abolishes most of the differences in adenylate cyclase activity observed with homogenates from control and opiate-treated cells. Cycloheximide blocked some, but not all, of the opiate-dependent increase in adenylate cyclase activity. These results suggest that the opiate-dependent increase in adenylate cyclase is due to conversion of adenylate cyclase to a form with altered activity. Protein synthesis also is required for part of the opiate effect. We propose that activity of adenylate cyclase determines the rate of conversion of the enzyme from one form to the other and that opiates, by inhibiting adenylate cyclase, alter the relative abundance of low- and high-activity forms of the enzyme.
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PMID:Opiate-dependent modulation of adenylate cyclase. 26 96

Nuclear RNA polymerase activity was studied in homotransplanted rat glial tumors where the primary tumor was produced by transplacental injection of ethylnitrosourea. Alpha amanitin, cycloheximide, and rifampicin were tested as inhibitors of this activity. Alpha amanitin significantly inhibited RNA polymerase activity in all tumors. This indicated that the major nuclear RNA polymerase activity seen in vitro in the tumor nuclei was RNA polymerase II. This is similar to the activity seen in normal glial nuclei. Cycloheximide and rifampicin which have no effect on RNA polymerase activity in normal glial nuclei inhibited about 20% of the polymerase activity in three of the tumors. The size and multiplicity of the nucleoli in these tumor cells suggests that RNA polymerase I could account for the activity which is inhibited by cycloheximide.
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PMID:RNA polymerase activity in homotransplanted rat brain tumors initially induced by ethylnitrosourea. 114 4

A model culture system of C6 rat glioma cells was used to test the involvement of cAMP in the regulation of the myelin PLP and MAG genes. The treatment of cells with isoproterenol (10(-5) to 10(-8) M) upregulated the expression of the PLP and MAG genes in a concentration-dependent manner. The mRNA for PLP reached a maximum (sevenfold higher than in control cells) after about 12-24 hr, then declined to approximately fourfold over the control level. The response of MAG gene was delayed by at least 36 hr, and the level of MAG mRNA reached a maximum of approximately 48-fold over the control level on the fourth day in culture. The co-administration of propranolol blocked the effect of isoproterenol, whereas 10(-5) M forskolin simulated the effect of isoproterenol, indicating a role of cAMP in the signal transduction cascades leading to upregulation of the myelin genes. However, the dissimilarity in the timing and the extent of upregulation of the PLP and MAG genes by cAMP-stimulating agents indicate the existence of different intracellular mechanisms for the activation of these two genes. Cycloheximide blocked the stimulatory effect of isoproterenol on both the PLP and MAG genes, indicating that the effect of cAMP on the myelin genes is mediated by protein product(s) of other cAMP-response gene(s).
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PMID:Cyclic AMP-induced upregulation of proteolipid protein and myelin associated glycoprotein gene expression in C6 cells. 137 8

The growth of rat glioma C6 cells, which provide an in vitro model of glial cells, is inhibited by retinoic acid and glucocorticoids, two agents which are important in brain differentiation and growth. To determine whether the growth-inhibitory effects of these agents are mediated by alterations in insulin-like growth factor I (IGF-I) production, the effects of retinoic acid and dexamethasone on IGF-I production and messenger RNA levels in C6 cells were investigated. IGF-I mRNA levels were determined using a solution hybridization/RNase protection assay. Treatment of C6 cells with dexamethasone or retinoic acid decreased IGF-I mRNA levels in a time-dependent fashion. The time course of the effect of the two agents differed, with the peak effect of dexamethasone between 6 and 12 h and the peak effect of retinoic acid at 27 h. In dose-response studies, IGF-I mRNA levels decreased to 27% of control levels (cells maintained in serum-free media) after treatment with 5 ng/ml dexamethasone, while half-maximal inhibition was achieved with approximately 0.5 ng/ml (1.4 nM) dexamethasone. Treatment with 10 microM retinoic acid decreased IGF-I mRNA levels to 24% of control levels with half-maximal inhibition occurring with approximately 0.5 microM retinoic acid. Cycloheximide prevented the inhibitory effect of these agents on IGF-I mRNA levels, suggesting that their effect is at least partly dependent upon protein synthesis. Immunoreactive IGF-I levels in media conditioned for 48 h by cells treated with dexamethasone or retinoic acid decreased to 32% and 42% of control levels, respectively. Treatment of C6 cells with retinoic acid or dexamethasone decreased thymidine incorporation into DNA. Treatment of cells with IGF-I alone had no effect on thymidine incorporation into DNA, but addition of 10 or 50 ng/ml IGF-I to dexamethasone-treated cells stimulated a small, but significant (P less than 0.01), increase in thymidine incorporation into DNA. IGF-I was not, however, able to reverse the inhibitory effect of retinoic acid. Finally, treatment of cells with 150 ng/ml of IGF binding protein 1 significantly decreased (P less than 0.01) thymidine incorporation into DNA by 17% as compared to incorporation into control cells maintained in serum-free media.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of insulin-like growth factor I production in rat C6 glioma cells: possible role as an autocrine/paracrine growth factor. 157 88

Cells that produce tumor necrosis factor-alpha (TNF-alpha) require the presence of signaling molecules since this cytokine is not normally expressed in a constitutive manner. It has been demonstrated that glial cells can produce TNF-alpha; however, the specific inducing molecules and their mechanism(s) of action have not been clearly defined. In this study, we examined the effect of human recombinant interleukin-1 beta (IL-1 beta) on the expression of TNF-alpha by CH235-MG human malignant glioma cells. CH235-MG cells do not constitutively express TNF-alpha mRNA or protein; however, upon stimulation with IL-1 beta, these cells synthesize and secrete biologically active TNF-alpha. IL-1 beta induces the expression of a 1.9 kb TNF-alpha mRNA species. Kinetic analysis demonstrated optimum TNF-alpha mRNA expression after a 4 h exposure to IL-1 beta, and peak TNF-alpha protein production at 18 h. Cycloheximide (CHX), an inhibitor of protein synthesis, markedly increased expression of TNF-alpha mRNA in IL-1 beta stimulated CH235-MG cells, indicating that de novo protein synthesis is not required for astroglioma TNF-alpha gene expression. Nuclear run-off analysis demonstrates that IL-1 beta causes transcriptional activation of the TNF-alpha gene, and CHX enhances IL-1 beta-induced TNF-alpha transcription. Studies of TNF-alpha mRNA stability using actinomycin D show that IL-1 beta-induced TNF-alpha mRNA has a half-life of approximately 30 min, and CHX increases the half-life of IL-1 beta-induced TNF-alpha mRNA to approximately 210 min. These results indicate that IL-1 beta, a cytokine present in the central nervous system during some pathological disease states, is a potent inducer of TNF-alpha in human malignant glioma cells.
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PMID:Interleukin-1 beta induction of tumor necrosis factor-alpha gene expression in human astroglioma cells. 173 80

The cellular distribution of active and inactive transglutaminase (TGase) was studied in C6 glioma cells before and during stimulation by a serum-containing medium. The activity of the enzyme was determined in the soluble and insoluble fractions obtained by freezing and thawing the cells, followed by centrifugation at 12,000g for 5 min. In the soluble fractions, the activity of TGase decreased 2.5 h post-stimulation and increased after 5 and 8 h. In the corresponding insoluble fractions, no significant changes in the activity of the enzyme were noted up to 8 h after stimulating the cells with fresh medium. An immunological approach was next used to determine the quantity of TGase antigen during the stimulation of the cultured glioma cells. In the soluble fraction, the quantity of the antigen decreases significantly at 2.5, 5, and 8 h. In contrast, in the insoluble fraction, a significant increase in TGase antigen was detected 8 h after the addition of fresh medium. Cycloheximide completely inhibited the increase in the quantity of TGase antigen in the insoluble fraction, 8 h post-stimulation, while actinomycin D caused a partial inhibition. Trypsin, neuraminidase, or Sendai viruses increased the activity of TGase significantly, when added to nonstimulated cells. Trypsin had no effect on TGase activity when added to the cells 2 h after stimulation with a serum-containing medium. These findings suggest that an inactive form of the enzyme is present in the insoluble cellular fraction. A model has been proposed to explain the variations in TGase activity, its distribution and translocation during cellular stimulation.
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PMID:Intracellular distribution of active and inactive transglutaminase in stimulated cultured C6 glioma cells. 287 48

The presence of insulin receptor and its regulation by butyrate and other short-chain fatty acids was studied in C6 cells, a rat glioma cell line. Intact C6 cells bind 125I-insulin in a rapid, reversible and specific manner. Scatchard analysis of the binding data gives typical curvilinear plots with apparent affinities of approx. 6 nM and 70 nM for the low-affinity (approx. 90% of total) and high-affinity (approx. 10% of total) sites respectively. Incubation with butyrate results in a time- and dose-dependent decrease of insulin binding to C6 cells. A maximal effect was found with 2 mM-butyrate that decreased the receptor by 40-70% after 48 h. Butyrate decreased numbers of receptors of both classes, but did not significantly alter receptor affinity. Other short-chain fatty acids, as well as keto acids, had a similar effect, but with a lower potency. Cycloheximide caused an accumulation of insulin receptors at the cell surface, since insulin binding increased and receptor affinity did not change after incubation with the inhibitor. Simultaneous addition of butyrate and cycloheximide abolished the loss of receptors produced by the fatty acid. In cells preincubated with butyrate, cycloheximide also produced a large increase in receptor numbers, showing that in the absence of new receptor synthesis a large pool of receptors re-appears at the surface of butyrate-treated cells.
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PMID:Presence of insulin receptors in cultured glial C6 cells. Regulation by butyrate. 293 May 2

The molecular mechanism of opiate receptor down-regulation and desensitization was investigated by studying the effects of cycloheximide and tunicamycin on opiate receptor activities in neuroblastoma X glioma NG108-15 hybrid cells. Cycloheximide inhibited [35S]methionine and [3H]-glucosamine incorporation by hybrid cells, while tunicamycin inhibited [3H]glucosamine incorporation only. Exposing hybrid cells to these two agents did not alter the viability of the cell. Treatment of NG108-15 cells with cycloheximide or tunicamycin produced a decrease in [3H]diprenorphine binding dependent on both time and concentrations of inhibitors, with no measurable modification in the ability of etorphine to regulate intracellular cyclic AMP production. Cycloheximide attenuated [3H]-diprenorphine binding by decreasing both the number of sites, Bmax, and the affinity of the receptor, Kd. Tunicamycin treatment produced a decrease in Bmax with no apparent alteration in Kd values. Cycloheximide and tunicamycin did not potentiate the rate or magnitude of etorphine-induced down-regulation or desensitization of opiate receptor in NG108-15 cells. Furthermore, there was an apparent antagonism in cycloheximide action on receptor down-regulation. The reappearance of opiate binding sites after agonist removal was affected by these two inhibitors. Cycloheximide and tunicamycin eliminated the increase in [3H]diprenorphine binding in the chronic etorphine-treated cells after agonist removal. These two inhibitors did not alter the resensitization of hybrid cells to etorphine. Thus, the site of opiate agonist action to induce receptor down-regulation and desensitization is not at the site of protein synthesis or protein glycosylation. These data substantiate previously reported observations that receptor down-regulation and receptor desensitization are two different cellular adaptation processes.
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PMID:Effects of cycloheximide and tunicamycin on opiate receptor activities in neuroblastoma X glioma NG108-15 hybrid cells. 298 31

We have examined insulin receptor regulation by glucocorticoids in the C6 rat glioma cell line. Dexamethasone decreased insulin binding to intact cell monolayers in a dose and time-dependent fashion. The effect is maximal between 48 and 72 h with 50 nM dexamethasone that decreased binding by 40-60%. The natural steroid corticosterone produced a similar effect although it was less potent, and the antiglucocorticoid 17 alpha-methyltestosterone was ineffective in lowering the receptor and partially antagonized the effect of dexamethasone. Total number of binding sites was decreased by glucocorticoids, and when analyzed with a two-site model a 3-fold increase in the dissociation constant (Kd) of the low affinity site was also observed. In the absence of protein synthesis the receptor accumulates at the cell surface, since cycloheximide produced a large increase of insulin binding. Cycloheximide totally blocked the effect of dexamethasone when both compounds were added together to the cells suggesting that protein synthesis is necessary for the effect of the glucocorticoid. By contrast, in cells pretreated with dexamethasone, cycloheximide was unable to produce an increase in cell surface receptor, showing that glucocorticoids probably deplete not only membrane receptor but also total cellular receptor.
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PMID:Glucocorticoids regulate insulin binding in a rat glial cell line. 329 39

Laminin promotes attachment and process formation in the neuroblastoma X glioma hybrid cell line NG108-15. As cells attached to laminin, they flattened and remained dispersed rather than associated in clumps. Process formation was observed within 1 hr after exposure to laminin and was dose dependent. Cycloheximide, an inhibitor of protein synthesis, did not block laminin-mediated attachment and neurite formation. Addition of drugs that depolymerize the cytoskeleton led to different behaviors for cells grown on plastic compared with those in the presence of laminin. Cells on plastic treated with either vinblastine or cytochalasin neither flattened nor grew processes. Cells plus laminin and vinblastine retracted processes, but remained flat, suggesting that laminin-induced processes can be destabilized by disrupting microtubules. Cells sequentially treated with laminin and cytochalasin produced processes that were thin and highly branched. Cells in high concentrations of cytochalasin on a laminin substrate formed aberrant processes even when their soma did not flatten. Since laminin counteracted the effect of cytochalasin on process outgrowth but did not alter the effect of cytochalasin on flattening of the cell body, different mechanisms mediated by microfilaments may be involved in cell flattening and in process formation.
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PMID:Effect of laminin and cytoskeletal agents on neurite formation by NG108-15 cells. 336 96


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