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)

Rat C6 glioma cells have both beta 1- and beta 2-adrenergic receptors in approximately 7:3 ratio. When the cells were exposed to the beta-adrenergic agonist isoproterenol, there was a rapid sequestration of up to 50% of the surface receptor population over a 30-min period as measured by the loss of binding of the hydrophilic ligand [3H] CGP-12177 to intact cells. Using the beta 1-selective antagonist CGP 20712A to quantify the proportion of the two subtypes, it was found that although both beta 1 and beta 2 receptors were sequestered, the latter were sequestered initially twice as fast as the former. More prolonged agonist exposure led to a down-regulation of approximately 90% of the total receptor population by 6 h as measured by the loss of binding of the more hydrophobic ligand [125I]iodocyanopindolol to cell lysates. The two subtypes, however, underwent down-regulation with similar kinetics. Treatment of the cells with agents that raise cyclic AMP levels such as cholera toxin and forskolin resulted in a slower, but still coordinated down-regulation of both subtypes. Thus, there appears to be both independent and coordinate regulation of endogenous beta 1-and beta 2-adrenergic receptors in the same cell line.
 ...
PMID:Independent and coordinate regulation of beta 1- and beta 2-adrenergic receptors in rat C6 glioma cells. 781 86

The present study describes identification and partial characterization of a glioma-derived high molecular weight transforming growth factor beta-like molecule (HMW-TGF beta) that requires no activation for biological activity. HMW-TGF beta, constitutively produced by the human glioma cell line, D54MG, is not acid- or heat-labile; is relatively resistant to denaturation, reduction, and high salt treatment. Monoclonal antibody 12A12.D7, produced against partially-purified HMW-TGF beta, was used both to deplete and to neutralize directly a > 158 kDa HMW-TGF beta activity from gel filtration fractions; the antibody also directly neutralized purified mature TGF beta 1. 12A12.D7 recognized a single protein species of 186 kDa from unlabeled glioma cell conditioned media and 35S-labeled lysates. HMW-TGF beta is not due to complex formation between TGF beta and any of the known carrier molecules. Production of HMW-TGF beta by glioma cells could facilitate tumor cell proliferation, and thus contribute to the inexorable and rapid progression that characterizes malignant gliomas.
 ...
PMID:Production of a bioactive high molecular weight transforming growth factor beta-like molecule by human malignant glioma cell lines. 785 59

Transforming growth factor beta 1 (TGF beta 1) inhibits cell proliferation in T24 glioma and 476-16 trigeminal neurinoma (Schwannoma) cells. In both cell types, the inhibition of cell proliferation is followed by cell rounding and detachment as well as internucleosomal DNA fragmentation, nuclear condensation and cell shrinkage, cellular changes that are characteristic for apoptosis. While the induction of apoptosis is closely coupled with the inhibition of cell proliferation in these tumor cells, the mode of apoptosis appears to differ between the two cell types. In 476-16 cells whose proliferation is highly susceptible to TGF beta 1, apoptosis occurs primarily after growth arrest at the G1 phase. Apoptotic cell death of 476-16 cells pretreated with TGF beta 1 is stimulated by serum deprivation, and it is inhibited by mitogenic growth factors such as insulin and platelet-derived growth factors. In T24 cells whose DNA replication is inhibited only moderately by TGF beta 1, apoptosis occurs in the presence of TGF beta 1 during the final cell division cycle when cells undergo density-induced growth arrest. While staurosporine accelerates TGF beta 1-induced apoptosis in both 476-16 and T24 cells, 12-O-tetradecanoylphorbol 13-acetate inhibits TGF beta 1-induced apoptosis of 476-16 cells but stimulates that of T24 cells. The present results suggest that TGF beta 1 may potentially be utilized for the management of neurogenic tumors of glial and Schwann cell origin.
 ...
PMID:Induction of apoptosis by transforming growth factor beta 1 in glioma and trigeminal neurinoma cells. 787 62

We studied the regulation of beta-adrenergic receptor (AR) subtypes co-existing in rat C6 glioma cells to clarify the importance of subtype ratio in responses to catecholamines. Radioligand binding studies with [125I]-cyanopindolol showed that beta 1- and beta 2-ARs co-existed in this cell line in approximately an 80:20 ratio. Norepinephrine (NE) and epinephrine (EPI) were equally potent in increasing cAMP accumulation, consistent with a primarily beta 1-response, although both beta 1- and beta 2-components of the response could be isolated using selective agonists (NE and zinterol), and antagonists (CGP 20712A and ICI 118,551). Little or no evidence of beta 3-ARs could be found in this cell line. Treatment of cells with 500 nM dexamethasone (DEX) for 48 hr increased the proportion of beta 2-ARs (20 to 60%). However, a reciprocal decrease in beta 1-ARs resulted in no change in total beta-ARs. Studies on the time-(12 to 72 hr) and concentration- (5 nM to 5000 nM) dependence of DEX treatment showed that increases in beta 2-ARs were closely linked to decreases in beta 1-ARs with little or no change in total receptor density observed at any time or in any concentration studied. Treatment with DEX also increased beta 2- and decreased beta 1-mediated cAMP responses, but did not alter the response to the nonselective agonist, isoproterenol. Northern blot analysis showed a 2- to 3-fold increase in beta 2-AR mRNA, but no change in beta 1-AR mRNA, after exposure to 50 or 500 nM DEX for 48 hr. Surprisingly, after DEX treatment, NE and EPI were still equally potent in activating cAMP accumulation, although responses to the beta 2-selective agonist, zinterol, were increased. These studies show a close reciprocal regulation by DEX of the relative proportions of beta 1- and beta 2-AR subtypes in C6 cells. The functional significance of the changing subtype ratios does not appear to be related to catecholamine responsiveness.
 ...
PMID:Close reciprocal regulation of beta 1- and beta 2-adrenergic receptors by dexamethasone in C6 glioma cells: effects on catecholamine responsiveness. 790 14

Microtubule disrupter, colchicine, and microtubule stabilizer, taxol, were used to determine whether microtubules play a role in beta-adrenergic receptor mRNA homeostasis and agonist-induced down-regulation in C6 glioma cells. Colchicine treatment had significant, differential, time-dependent effects on constitutive beta 1- and beta 2-adrenergic receptor mRNA levels. These effects stemmed from the action of colchicine on microtubules, because beta-lumicolchicine, an inactive isomer, had no effect, and nocodazole, a structurally unrelated microtubule disrupter, had similar effects. Colchicine treatment had little effect on the total number of beta-adrenergic receptor binding sites as measured by (-)-[125I]iodopindolol binding, but did alter the relative proportion of beta 1- and beta 2-adrenergic receptor subtypes. Colchicine also had no effect on basal cyclic AMP levels. In contrast to colchicine, taxol treatment had little long-term effect on either beta 1- or beta 2-adrenergic receptor mRNA levels. Taxol antagonized the effects of colchicine on total binding and mRNA levels. Taxol treatment increased basal cyclic AMP levels fourfold and potentiated (-)-isoproterenol-induced cyclic AMP production. Colchicine pretreatment completely inhibited (-)-isoproterenol-induced down-regulation of beta 1-adrenergic receptor mRNA, but not that of beta 2-adrenergic receptor mRNA. Taxol pretreatment had little effect on isoproterenol-induced beta-adrenergic receptor mRNA down-regulation. Colchicine pretreatment also attenuated isoproterenol-induced receptor down-regulation and inhibited agonist-stimulated cyclic AMP production. These effects of colchicine were antagonized by taxol. Whereas the effects of taxol and colchicine on isoproterenol-induced down-regulation of beta-adrenergic receptor mRNA are consistent with their effects on cyclic AMP production, those of colchicine in the absence of stimulation must involve other mechanisms. The data demonstrate that the state of microtubule assembly can affect cyclic AMP levels, beta 1- and beta 2-adrenergic receptor mRNA, and binding site levels in C6 glioma cells.
 ...
PMID:Regulation of beta-adrenergic receptor mRNA in rat C6 glioma cells is sensitive to the state of microtubule assembly. 790 23

Exposure of rat C6 glioma cells to either agonists or agents that increase cyclic AMP levels leads to down-regulation of beta 1-adrenergic receptors (beta 1 AR) as measured by loss of radioligand binding sites. The present study examines the influence of isoproterenol and forskolin treatment on levels of beta 1 AR mRNA, mRNA stability, and gene transcription rate. Isoproterenol treatment of C6 cells altered beta 1 AR mRNA levels in a biphasic manner; i.e., short-term exposure (30-60 min) increased by 50%, whereas longer exposure (2-6 h) decreased by 50% the levels of beta 1 AR mRNA. The extent of both the up- and down-regulation was dependent on agonist concentration. Similar regulation of beta 1 AR mRNA was observed in forskolin-treated cells. Pretreatment of the cells with Pseudomonas exotoxin A, a potent inhibitor of protein synthesis, completely blocked isoproterenol- and forskolin-mediated down-regulation of beta 1 AR mRNA, and thereby potentiated the increase in receptor mRNA up to fourfold over the 6-h time course. The mechanisms underlying beta 1 AR mRNA down-regulation were examined. The half-life of beta 1 AR mRNA was slightly increased (from 61 to 77 min) after a 2-h exposure of the cells to either isoproterenol or forskolin. Nuclear run-on analysis demonstrated that the rate of beta 1 AR gene transcription was increased after isoproterenol incubation for 60 min, but then decreased after 90-240 min, consistent with the time course for up- and down-regulation of beta 1 AR mRNA. Isoproterenol treatment (120 min) also decreased the level of beta 1 AR nascent transcripts, purified by affinity chromatography of RNA isolated from 4-thiouridine-pulsed cells. The results demonstrate that beta 1 AR mRNA has a relatively short half-life and that agonist regulation of beta 1 AR mRNA is mediated by activation of the cyclic AMP system. Moreover, the results indicate that agonist regulation of beta 1 AR mRNA occurs at the level of beta 1 AR gene transcription, not mRNA stability. Finally, the observed requirement for protein synthesis indicates that beta 1 AR mRNA down-regulation may be mediated by the induction of a repressor of the beta 1 AR gene.
 ...
PMID:Agonist and cyclic AMP-mediated regulation of beta 1-adrenergic receptor mRNA and gene transcription in rat C6 glioma cells. 793 20

A protein was isolated from rat C6 glioma-conditioned medium and was biochemically characterized. The heparin-binding protein has a native molecular mass of 55-75,000 Da, a molecular mass of 40-48,000 Da under denaturing conditions, and a pI of 5.0-6.0. Based on the determined partial amino acid sequences, the full lenght cDNA encoding the rat and human proteins were cloned. The cDNA sequences identified the isolated rat and human protein as the homologue of a recently reported mouse osteoblast-transforming-growth-factor-beta 1-inducible protein, encoded by the TSC-36 gene [Shibanuma, M., Mashimo, J., Mita, A., Kuroki, T. & Nose, K. (1993) Eur. J. Biochem. 217, 13-19]. Analysis of the human, rat and mouse amino acid sequences indicates that these proteins are highly conserved (> 92% sequence identity). Sequence similarities with follistatin and the follistatin-like domain of agrin are revealed. The relationship with follistatin and agrin points to possible common functions for the cloned follistatin-related proteins (FRP). The protein has no effect on the inhibitory action of transforming growth factor-beta 1, on CCl-64 cell growth.
 ...
PMID:Characterization of a rat C6 glioma-secreted follistatin-related protein (FRP). Cloning and sequence of the human homologue. 795 30

A unique characteristic of astrocytic malignancies is their frequent dissemination through the brain. Cellular determinants of migration include adhesion to the substratum, restructuring of the actin cytoskeleton to generate motion, and (in the setting of invasion into tissue) secretion of enzymes for remodeling interstitial space to accommodate forward motion of the migrating cell. In order to better understand these features in the context of local brain invasion by astrocytoma cells, the adhesion and migratory properties of these cells have been investigated in an in vitro monolayer system. Adhesion of 8 different astrocytoma cell lines to different purified human extracellular matrix (ECM) proteins (collagen type IV, cellular fibronectin, laminin, and vitronectin) revealed that there is no "astrocytoma-specific" ECM protein that consistently leads to high cell binding. Similarly, migration of astrocytoma cells was found to be variable and dependent on different ECM proteins. Laminin was frequently the most permissive for adhesion and migration. Adhesion to collagen, fibronectin, and vitronectin was integrin dependent and could be blocked using anti-beta 1 integrin antibodies; in contrast, attachment to laminin could not be blocked using these antibodies. A comparison of adhesion with migration for each of the cell lines on each of the 4 ECM proteins revealed that poor adhesion was associated with minimal migration and that frequently, high adhesion was correlated with rapid migration. When tested for migration on autologous, cell-derived ECM, none of the cell lines were as migratory as they were on one of the purified ECM proteins, with the exception of SF767 cells. Furthermore, it was found that ECM from SF767 cells promoted the migration of other astrocytoma cells. The results from this study indicate that migration is a constitutive behavior of glioma cells which is dependent on, or modified by, the presence or absence of permissive ligands in the environment.
 ...
PMID:Determinants of human astrocytoma migration. 803 13

We raised polyclonal antibodies against the C-terminal peptides of protein kinase C (PkC) subspecies alpha, beta 1, beta 2, gamma, delta, epsilon, and zeta and checked their specificity against brain extracts using Western immunoblot analysis. With equal amounts of protein applied to gels PkC subspecies beta 1, delta, epsilon and zeta were detected in primary cultures of mixed glial cells: bands for the alpha and beta 2 subspecies were less prominent. PkC gamma was not detected in primary glial cultures. The epsilon and zeta subspecies of PkC were detected in subcultures of type 1 astrocytes with weaker bands for the alpha, beta 1 and beta 2 subspecies. Blots of O-2A-lineage glia contained PkCs delta and zeta as prominent bands: the alpha, beta 1 and epsilon subspecies were also present. All PkC subspecies including PkC gamma were detected in C6 glioma cells.
 ...
PMID:Rat brain glial cells in primary culture and subculture contain the delta, epsilon and zeta subspecies of protein kinase C as well as the conventional subspecies. 808 70

The expression of beta 2-adrenergic receptors is up-regulated by glucocorticoids. In contrast, beta 1-adrenergic receptors display glucocorticoid-induced down-regulation. In rat C6 glioma cells, which express both of these subtypes of beta-adrenergic receptors, the synthetic glucocorticoid dexamethasone stimulates no change in the total beta-adrenergic receptor content, but rather shifts the beta 1:beta 2 ratio from 80:20 to 50:50. Radioligand binding and immunoblotting demonstrate a sharp decline in beta 1-adrenergic receptor expression. Metabolic labelling of cells with [35S]-methionine in tandem with immunoprecipitation by beta 1-adrenergic-receptor-specific antibodies reveals a sharp decline in the synthesis of the receptor within 48 h for cells challenged with glucocorticoid. Steady-state levels of beta 1-adrenergic-receptor mRNA declined from 0.47 to 0.26 amol/microgram of total cellular RNA within 2 h of dexamethasone challenge, as measured by DNA-excess solution hybridization. The stability of receptor mRNA was not influenced by glucocorticoid; the half-lives of the beta 1- and beta 2-subtype mRNAs were 1.7 and 1.5 h respectively. Nuclear run-on assays revealed the basis for the down-regulation of receptor expression, i.e. a sharp decline in the relative rate of transcription for the beta 1-adrenergic-receptor gene in nuclei from dexamethasone-treated as compared with vehicle-treated cells. These data demonstrate transcriptional suppression as a molecular explanation for glucocorticoid-induced down-regulation of beta 1-adrenergic receptors.
 ...
PMID:Glucocorticoids down-regulate beta 1-adrenergic-receptor expression by suppressing transcription of the receptor gene. 809 90


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