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)

Human T-cell lymphotropic virus type I (HTLV-I), an etiologic agent for adult T-cell leukemia, is strongly associated with certain neurological diseases. The HTLV-I genome encodes a protein, Tax1, that transactivates viral gene transcription. CD4-positive T helper lymphocytes express the proenkephalin gene, and enkephalins have been implicated as neuroimmunomodulators. We have investigated the effect of Tax1 on the proenkephalin gene promoter in C6 rat glioma cells and demonstrated its transactivation. Analysis using 5' deletion mutants of the promoter region showed that sequences upstream of base pair -190 are necessary for maximal transactivation. Forskolin, a cAMP modulator, synergistically increased Tax1-mediated transactivation of the proenkephalin promoter. Neither Tax1 transactivation alone nor Tax1/cAMP synergism exclusively involved cAMP-responsive elements. Endogenous proenkephalin gene expression increased in Tax1-expressing C6 cells. Since HTLV-I infects lymphocytes, which express proenkephalin mRNA, Tax1 transregulation of proenkephalin expression may provide bidirectional communication between the nervous and immune systems in HTLV-I-related diseases.
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PMID:Transactivation of the proenkephalin gene promoter by the Tax1 protein of human T-cell lymphotropic virus type I. 173 81

Some human tumor cell lines express the c-sis gene, the proto-oncogene of the transforming gene v-sis, and produce platelet-derived growth factor, which may contribute to carcinogenesis by autocrine or paracrine mechanisms. Here we demonstrate that c-sis expression in some human glioma and osteosarcoma cell lines can be blocked by agents that increase cellular cyclic adenosine monophosphate (cAMP). Forskolin, 8-bromocyclic AMP, cholera toxin, and prostaglandin E1 reduced c-sis mRNA in these cells by up to 90%. c-sis transcription rates were reduced by agents that increase cAMP; the stability of c-sis mRNA was unaffected. The possible therapeutic value of blocking the expression of tumor growth factor genes pharmacologically warrants further study.
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PMID:Cyclic AMP blocks expression of the c-sis gene in tumor cells. 254 92

Cultured C6 rat glioma cells contain mRNA coding for preproenkephalin (A), the precursor of methionine- and leucine-enkephalin. The abundance in untreated cells was determined by blot hybridization methods to be 3-6 pg per micrograms total RNA. Treatment of confluent cells for 12 h with 10 microM (-)-norepinephrine, which activates C6 adenylate cyclase, transiently elevated preproenkephalin mRNA to 3.3 and 7.7 times the control in the absence and presence of the glucocorticoid dexamethasone, respectively. Hydrocortisone and corticosterone also potentiated the effect of norepinephrine. However, glucocorticoids alone did not alter the preproenkephalin mRNA abundance. The effect of norepinephrine + dexamethasone was blocked by the beta-adrenergic antagonist propranolol but not by the alpha-adrenergic antagonist phentolamine. Forskolin, which directly activates adenylate cyclase, similarly elevated the preproenkephalin mRNA abundance; its effect was also potentiated by dexamethasone. C6 cells contain Met-enkephalin-containing protein resembling proenkephalin (apparent Mr 30,000) but little Met-enkephalin, suggesting a low level of proper precursor processing. Treatment with norepinephrine + dexamethasone raised the content of proenkephalin-like protein 11-fold. Thus, preproenkephalin mRNA levels in C6 cells are regulated synergistically by adenosine 3':5'-cyclic monophosphate and glucocorticoids. These results suggest modes of regulation of proenkephalin biosynthesis in normal rat enkephalinergic cells.
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PMID:Expression of the enkephalin precursor gene in C6 rat glioma cells: regulation by beta-adrenergic agonists and glucocorticoids. 287 71

We have compared the effects of norepinephrine, forskolin, and dibutyryl cyclic AMP (Bt2cAMP) on the regulation of the cytosolic enzyme glycerol phosphate dehydrogenase (GPDH) in the C6 rat glioma cell line. Forskolin and Bt2cAMP elicit a dose-dependent increase in the levels of the enzyme that was, however, unaffected by norepinephrine. The half-maximal effect of forskolin was obtained at 7-8 microM, and the effect was maximal at 30 microM. Dexamethasone at a 50 nM concentration produced a two- to sixfold induction of GPDH after 48 h. The combination of dexamethasone with forskolin or Bt2cAMP leads to an elevation in GPDH levels that is higher than that produced by one of the compounds alone. This potentiation is found when both agents are added together with or after the glucocorticoid. The increase in uninduced and dexamethasone-induced GPDH activity was blocked by cycloheximide and actinomycin D, indicating that de novo protein and RNA synthesis are required. The activity of cytosolic lactate dehydrogenase activity did not change after incubation with dexamethasone, but increased with forskolin or Bt2cAMP.
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PMID:Regulation of glycerol phosphate dehydrogenase and lactate dehydrogenase activity by forskolin and dibutyryl cyclic AMP in the C6 glial cells. 302 Jan 71

The neuroblastoma-glioma NG108 cell line has been shown to contain both a delta-opiate receptor and enkephalin peptides. In this paper, the presence of authentic proenkephalin mRNA and proenkephalin-derived peptides are demonstrated. Growth of the cells in the presence of etorphine for 5-7 days resulted in a 3-fold increase of proenkephalin mRNA, which was accompanied by comparable increases in proenkephalin peptides and free enkephalin. The effect was mimicked by either morphine or [D-Ala2,D-Met5]enkephalinamide, and was blocked by naloxone. The EC50 for the effect of etorphine was 10(-9) M. The cyclic AMP content of cells grown for 5 days in the presence of etorphine was the same as that of control cells. Forskolin treatment also increased the proenkephalin mRNA content of the cells: the effect was not additive with that of etorphine, suggesting that the effect of opiate agonists was not occurring through their inhibition of adenylate cyclase. The results suggest that proenkephalin synthesis in NG108 cells can be regulated by two different mechanisms, one involving cyclic AMP while the other, regulated by the opiate receptor, is yet to be determined.
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PMID:Chronic exposure to opiate agonists increases proenkephalin biosynthesis in NG108 cells. 338 39

We have examined the roles that cyclic AMP and protein synthesis play in the development of refractoriness in C6-2B rat glioma cells using the diterpene, forskolin, a general activator of cyclic AMP-generating systems. Forskolin-stimulated cyclic AMP accumulation peaked at 30 min and declined thereafter to 10% of peak levels by 3 hr despite the continued presence of sufficient forskolin to produce 98% of the control response when the incubation medium was transferred to naive cells. C6-2B cells treated for 3 hr with forskolin were refractory to a subsequent challenge with forskolin or isoproterenol. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) increased the degree of refractoriness developed after forskolin treatment. In the presence of IBMX, the induction of refractoriness by forskolin and forskolin-stimulated cyclic AMP accumulation were similarly dependent on forskolin concentration. Pre-treatment with isoproterenol or the cyclic AMP analogue, dibutyryl cyclic AMP, induced refractoriness to forskolin. When C6-2B cells were pre-treated with forskolin plus the protein synthesis inhibitor, cycloheximide, the development of refractoriness to forskolin or isoproterenol was attenuated. Cycloheximide prevented isoproterenol- or dibutyryl cyclic AMP-induced refractoriness to forskolin. These data provide further evidence that the onset of the refractory state in C6-2B cells is mediated by cyclic AMP and is a protein synthesis-requiring process.
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PMID:Forskolin-stimulated cyclic AMP accumulation mediates protein synthesis-dependent refractoriness in C6-2B rat glioma cells. 619 88

We have identified and studied a posttranscriptional mechanism of lactate dehydrogenase A (LDH) subunit gene expression at the level of mRNA stability. Using the well differentiated rat C6 glioma cell line as a model system, the effects of activators of the protein kinase A and C pathways on the half-life of LDH A mRNA were measured by two independent methods: 1) by the RNA synthesis inhibitor-chase method using actinomycin D, and 2) by analysis of decay of LDH A [3H]mRNA in [3H]uridine-labeled cells. By each method, the half-life of relatively short-lived LDH A mRNA was increased 5- to 7-fold in 8- (4-chloro-phenylthio) cAMP or forskolin-treated and about 3-fold in 12-0-tetradecanoylphorbol-13- acetate (TPA) or dioctanoylglycerol-treated cells. Forskolin acted synergistically with TPA to prolong LDH A mRNA half-life from 55 min to more than 20 h. The relatively rapid basal decay rate of LDH A mRNA was also considerably slowed in the presence of the protein phosphatase inhibitor okadaic acid, suggesting a functional role for protein phosphorylation in the stabilization process. In glioma cells stably transformed with a protein kinase A catalytic subunit expression vector, overexpression of the catalytic subunit stabilized LDH mRNA to the degree seen in forskolin-treated cells. In cells transfected with a protein kinase A inhibitor-expression vector, cAMP-mediated stabilization of LDH A mRNA half-life was prevented. Furthermore, both staurosporin and 3- [1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol- 3-yl)- maleimide, inhibitors of protein kinase C, prevented the TPA-induced stabilization of LDH A mRNA. We conclude from the experimental data that the protein kinase A and C signal pathways play an active functional role in regulating LDH A mRNA stability and act cooperatively to achieve LDH A mRNA stability regulation.
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PMID:Lactate dehydrogenase A subunit messenger RNA stability is synergistically regulated via the protein kinase A and C signal transduction pathways. 747 96

Recently we identified three novel Schwann cell mitogens named GGF (glial growth factor)-I (34 kDa), GGF-II (59 kDa), and GGF-III (45 kDa), and provided evidence that they are three distinct but structurally related members of a larger family of factors, which includes heregulin, neu differentiation factor, and acetylcholine receptor-inducing activity (ARIA). We report here the characterization of the mitogenic and trophic activities for all three forms of GGF on rat Schwann cells and several other cell types. GGF-I, GGF-II, and GGF-III are potent mitogens for rat Schwann cells in vitro at nanomolar concentrations, whereas at lower concentrations they promote Schwann cell survival, in the absence of cAMP elevating agents. Forskolin, an adenylate cyclase activator, potently synergizes with the GGFs by an indirect mechanism, possibly involving transcriptional activation of GGF receptor(s). In addition, the GGFs stimulate DNA synthesis in rat glioma C6 cells, and in SK-BR-3 cells, which overexpress the p185 neu/erbB2. Fibroblasts obtained from different sources are weakly stimulated by GGFs, whereas PC12 cells are unable to respond under a variety of experimental conditions. These observations are consistent with the proposal that GGF-I, GGF-II, and GGF-III are a set of potent glial cell mitogens and putative ligands of members of the EGF receptor family, namely p185 neu/erbB2, p160/erbB3, and p180/erbB4, which may play important roles in the development, regeneration, and tumor biology of the peripheral nervous system.
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PMID:Glial growth factors I-III are specific mitogens for glial cells. 898 98

P2Y receptors inhibiting adenylyl cyclase have been found in blood platelets, glioma cells, and endothelial cells. In platelets and glioma cells, these receptors were identified as P2Y(12). Here, we have used PC12 cells to search for adenylyl cyclase inhibiting P2Y receptors in a neuronal cellular environment. ADP and ATP (0.1 - 100 microM) left basal cyclic AMP accumulation unaltered, but reduced cyclic AMP synthesis stimulated by activation of endogenous A(2A) or recombinant beta(2) receptors. Forskolin-dependent cyclic AMP production was reduced by <or=1 microM and enhanced by 10 - 100 microM ADP; this latter effect was turned into an inhibition when A(2A) receptors were blocked. The nucleotide inhibition of cyclic AMP synthesis was not altered when P2X receptors were blocked, but abolished by pertussis toxin. The rank order of agonist potencies for the reduction of cyclic AMP was (IC(50) values): 2-methylthio-ADP (0.12 nM)=2-methylthio-ATP (0.13 nM)>ADPbetaS (71 nM)>ATP (164 nM)=ADP (244 nM). The inhibition by ADP was not antagonized by suramin, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid, or adenosine-3'-phosphate-5'-phosphate, but attenuated by reactive blue 2, ATP(alpha)S, and 2-methylthio-AMP. RT - PCR demonstrated the expression of P2Y(2), P2Y(4), P2Y(6), and P2Y(12), but not P2Y(1), receptors in PC12 cells. In Northern blots, only P2Y(2) and P2Y(12) were detectable. Differentiation with NGF did not alter these hybridization signals and left the nucleotide inhibition of adenylyl cyclase unchanged. We conclude that P2Y(12) receptors are expressed in neuronal cells and inhibit adenylyl cyclase activity.
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PMID:Inhibition of adenylyl cyclase by neuronal P2Y receptors. 1183 15

Inducible nitric oxide synthase (iNOS) plays a significant role in the pathology of central nervous system diseases. Inducible NOS expression is regulated by intracellular adenosine 3',5'-cyclic monophosphate (cAMP) signaling, and astrocytes contain both iNOS and adenylate cyclase-coupled neurotransmitter receptors. The data obtained from the present study indicated that acetylcholine, lambda-amino-n-butyric acid, glutamate, quinolinic acid, N-methyl-D-aspartate and aspartate have no effect on NO(2)(-) production in C6 glioma cells stimulated by lipopolysaccharide and interferon-gamma. However, dopamine (DA) caused inhibition of NO(2)(-) production and iNOS transcription. The effects of DA were not due to homovanillic acid/3,4-dihydroxyphenylacetic acid, the autoxidative products superoxide (O(2)(-))/hydrogen peroxide (H(2)O(2)) or direct reactions with NO(2)(-). Forskolin, adenylate cyclase activator, dose-dependently reduced NO(2)(-). Meanwhile, (+/-) SKF-38393 D(1) receptor agonist attenuated iNOS in a similar fashion to DA. In addition, the results indicated that DA attenuation of iNOS was significantly impeded by the adenylate cyclase inhibitor MDL-12,330A, the D(1) antagonist SCH-23390, the beta2 adrenergic receptor antagonist ICI-118,551 and the beta1 adrenergic receptor antagonist atenolol. In conclusion, it appears that DA attenuates iNOS through a D(1), beta1 and beta2 adrenergic receptor-linked adenylate cyclase-mediated cAMP cascade.
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PMID:Characterization of neurotransmitters and dopamine attenuation of inducible nitric oxide synthase in glioma cells. 1245 38


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