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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel clonal cell line derived from a human glioma (HOG) was found to express some oligodendrocyte-specific proteins including a 15-kDa form of myelin basic protein (MBP) and high 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) activity. Expression of the myelin lipids galactosylceramide and sulfogalactosylceramide (sulfatide) was low. HOG cells did not express the characteristic astrocyte markers glial fibrillary acidic protein (GFAP) or significant glutamine synthetase (GS) activity. After initial plating, HOG cells were flat and epitheloid and thus showed a limited oligodendrocyte-like morphology. However, after cells became more confluent, some cells were phase-bright and elaborated short processes. Receptor types expressed by HOG cells included A2-adenosine, prostaglandin E1 (PGE1), and beta 2-adrenergic receptors (beta-ARs) linked to stimulation of adenylate cyclase, and muscarinic cholinergic and H1-histamine coupled to phosphatidyinositol turnover (Post and Dawson, 1991). HOG cells should therefore provide a useful model for studying the extracellular regulation and phosphorylation of oligodendrocyte-specific proteins.
Mol Chem Neuropathol 1992 Jun
PMID:Characterization of a cell line derived from a human oligodendroglioma. 132 95

The linkage between the transmembrane signal transduction system utilized by endothelin and alterations in gene expression has been investigated in C6 glioma cells. Treatment of C6 cells with endothelin-1 caused a rapid and transient 5-fold increase in c-fos and c-jun mRNA levels, followed by a decrease at 4 h. Dose-response studies indicated that 1 nM endothelin-1 caused half-maximal induction of c-fos mRNA 0.5 h after treatment and that maximal induction was elicited with a concentration of 10 nM. Actinomycin D totally abolished the rapid increase in c-fos mRNA caused by endothelin, indicating that the effect is at the transcriptional level. Endothelin-1 caused a decrease in proenkephalin mRNA to 50% of control levels at 4 h after treatment and had no effect on histone H4 mRNA over a 24 h period that was examined. These data indicate that receptor binding of endothelin-1 leads to rapid changes in the expression of immediate-early response genes which may cause more prolonged changes in the expression of AP-1 and/or CREB target genes in the nervous system.
Brain Res Mol Brain Res 1992 Jul
PMID:Stimulation of c-fos and c-jun gene expression and down-regulation of proenkephalin gene expression in C6 glioma cells by endothelin-1. 133 50

Protein kinase C (PKC) activation was examined for its role in delta-opioid receptor down-regulation in the neuroblastoma X glioma hybrid cell line NG108-15. Incubation of NG108-15 cells for 2 hr at 37 degrees with up to 1 microM 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), a phorbol ester that activates PKC, had no effect on opioid binding to membranes prepared from these cells. However, as little as 3 nM PMA incubated with an opioid agonist and NG108-15 cells potentiated the decrease and the rate of decrease of opioid binding, compared with agonist alone. Scatchard analysis of [3H][D-Ala2,D-Leu5]enkephalin (DADLE) binding revealed that NG108-15 cells incubated for 3 hr with 1 nM DADLE and 30 nM PMA displayed a > 50% reduction in the number of [3H]DADLE binding sites with no affinity change at the remaining sites, compared with cells treated with DADLE alone. The antagonist naloxone blocked both DADLE-induced and PMA-enhanced DADLE-induced down-regulation. The agonists morphine and cyclazocine, which alone were unable to induce delta receptor down-regulation, did so in the presence of PMA. The PKC inhibitor staurosporine and down-regulation of PKC by chronic PMA treatment blocked PMA potentiation of DADLE-induced down-regulation, but not "normal" DADLE-induced down-regulation. The enhancement of down-regulation by PMA was unaffected by either metabolic inhibitor or incubations at 20 degrees, conditions that blocked down-regulation by DADLE alone. NG108-15 cells incubated with [3H]DADLE and PMA retained more [3H]DADLE than cells incubated with [3H]DADLE alone, suggesting that PMA enhanced receptor internalization instead of merely inhibiting membrane binding. The diacylglycerol 1-oleoyl-2-acetyl-glycerol and bradykinin substituted for PMA but not carbachol, indicating that PKC activated physiologically may play a role in delta receptor down-regulation.
Mol Pharmacol 1992 Oct
PMID:Protein kinase C activation increases the rate and magnitude of agonist-induced delta-opioid receptor down-regulation in NG108-15 cells. 133 57

Interactions between beta-adrenergic and ADP purinergic receptors in C6 glioma cell membrane preparations were investigated under steady state and then pre-steady state conditions of adenylyl cyclase (EC 4.6.1.1) activity, in order to determine how fast the second receptor antagonizes the transduction mechanism of the first. Cell membranes were washed to deplete them as thoroughly as possible of low molecular weight compounds, especially ATP and ADP, and to ensure better control of both substrate and agonist nucleotide concentrations. ATP concentrations were kept constant with the use of an ATP-regenerating system; the C6 cell line exhibited very active ectonucleotidases. The purinergic agonist ADP was replaced by its nonhydrolyzable congener adenosine 5'-O-(2-thio)diphosphate (ADP beta S), which was demonstrated, like ADP, to inhibit isoproterenol-stimulated adenylyl cyclase activity in intact cells (IC50 for ADP, 0.5 +/- 0.1 microM; IC50 for ADP beta S, 25 +/- 2 microM) and in membrane preparations (IC50 for ADP beta S, 79 +/- 20 microM). In the case of membrane preparations, ADP beta S did not compete with ATP, the substrate of the cyclase-catalyzed reaction, and behaved apparently as a non-competitive inhibitor of the enzyme. The pre-steady state kinetics of isoproterenol-stimulated adenylyl cyclase activity measured with a pulsed quenched-flow apparatus have previously been shown to include two steps, the first very rapid (taking place within 1-2 sec) and giving rise to a burst of cAMP synthesis and the second much slower and corresponding to the steady state reaction. ADP beta S inhibited the occurrence of both steps with comparable IC50 values (mean value, 55 +/- 20 microM). In the presence of increasing concentrations of the purinergic receptor agonist, the time constant of the exponential burst reaction was not affected, but its amplitude progressively decreased to zero. These results showed that the extinction of the beta receptor cAMP response by the purinergic ADP receptor occurred within the dead-time of the pulsed quenched-flow apparatus, which was 50 msec. Such a rapid inhibition of cAMP production excluded modulation of isoproterenol-stimulated adenylyl cyclase activity by the ADP receptor by a pathway other than its direct negative coupling to the cyclase via a Gi protein. In this respect, the P2 purinergic ADP receptor of the C6 glioma cell line appears comparable to the P2t receptor of platelets.
Mol Pharmacol 1992 Dec
PMID:Pre-steady state study of beta-adrenergic and purinergic receptor interaction in C6 cell membranes: undelayed balance between positive and negative coupling to adenylyl cyclase. 133 11

The synthesis of nerve growth factor (NGF) and nerve growth factor receptor (NGFR) were studied in a C6 glioma cell line by Northern blot hybridization. In response to a glutamate agonist N-methyl-D-aspartic acid (NMDA), NGF mRNA increased by up to 2-fold after 4-12 h of culture. The non-NMDA receptor agonists, quisqualate and kainate, did not induce any increase of NGF mRNA, and kainate actually produced a decrease. The increase in NGF mRNA in response to NMDA was dose-dependent at 1, 5 and 10 microM. NGF receptor (NGFR) mRNA showed changes in expression which were similar to those for NGF mRNA, but were less marked. The specific glutamate antagonist 2-aminophosphonovaleric acid (APV) blocked the increase of NGF mRNA produced by NMDA. In the absence of Ca2+, an increase of NGF mRNA was still observed but in the presence of 1 mM ethylglycol-bis-(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA), NGF mRNA production abolished. The mechanism producing an increase in NGF mRNA by NMDA may be mediated by cyclic AMP since intracellular cyclic AMP and NGF mRNA levels both increased following treatment with NMDA or dibutyryl cyclic AMP.
Brain Res Mol Brain Res 1992 Jun
PMID:Regulation of nerve growth factor and nerve growth factor receptor production by NMDA in C6 glioma cells. 135 54

Somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred tumors. SS-R were found in most neuroendocrine tumors, i.e. GH and TSH producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas. SS-R were also expressed in a majority of malignant lymphomas, in several brain tumors (all meningiomas, most astrocytomas) and in breast tumors. The majority of tumors expressing SS-R are rather differentiated (i.e. astrocytomas vs glioblastomas), but exceptions exist (high grade malignant lymphomas). An inverse relationship exists between SS-R and receptors for epidermal growth factor (EGF-R) incidence in lung tumors, glial tumors and most breast tumors, whereas meningiomas express simultaneously both receptors. A minority of tumors (ovarian tumors, MTC, insulinomas) express a subtype of SS-R, characterized by low affinity for the octapeptide SS analog octreotide. The function mediated by SS-R in human tumors may differ according to the tumor type. SS-R in pituitary and GEP tumor mediate hormone secretion inhibition with, in addition, possibly some antiproliferative effects. In meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate cyclase activity, and weakly stimulates proliferation. Whereas SS-R seem to mediate antiproliferative effects in animal models and cell lines of lymphomas, breast and lung tumors, such an effect has not yet been convincingly documented in human primary tumors. The clinical implications of the presence of SS-R in tumors are manyfold: (1) as a predictive marker for efficient therapy with octreotide in pituitary and GEP tumors; (2) as a diagnostic marker: for pathobiochemical classification of tumors, using in vitro detection methods; for clinical evaluation using in vivo scanning techniques; (3) as a prognostic marker; and (4) as a potential radiotherapeutic target.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. 135 16

C6 rat glioma cells were utilized as a model system to probe the 'serotonin/norepinephrine link' at the level of preproenkephalin (PPE) gene expression. The beta adrenoceptor mediated increase in PPE mRNA was attenuated by the selective beta 1 adrenoceptor antagonist metoprolol which blocked the isoproterenol induced cyclic AMP generation by 97%. The subtype nonspecific antagonist propranolol blocked both the isoproterenol induced increase in cyclic AMP and the increase in the PPE mRNA steady-state levels. Serotonin (5-HT) had no effect on the density of beta adrenoceptors or their down-regulation by isoproterenol and did not alter the PPE gene expression in the absence of the beta signal. However, 5-HT significantly deamplified the beta signal mediated enhancement of the PPE mRNA thus indicating that the aminergic link occurs beyond the beta adrenoceptor.
Brain Res Mol Brain Res 1992 Dec
PMID:The 'serotonin/norepinephrine link' beyond the beta adrenoceptor. 136 25

Operationally specific monoclonal antibodies (MAbs) reactive with tumor but not normal adult tissues offer great potential for diagnosis and therapy of CNS neoplasms. Two targets for specific MAb localization were chosen for this study: (1) glioma-associated gangliosides GM2 [II3NeuAc-GgOse3Cer], GD2 [II3(NeuAc)2-GgOse3Cer], GD3[II3(NeuAc)2-LacCer], 3'-isoLM1 [IV3NeuAc-LcOse4Cer], and 3',6'-isoLD1 [IV3NeuAc,III6NeuAc-LcOse4Cer] and (2) epidermal growth factor receptor (EGFR) variant molecules. Epitopic specificity of isolated ganglioside hybridomas was determined with FAB-MS defined ganglioside standards. All MAb are IgM. Assay of 14 cytologic specimens and 31 frozen sections of primary CNS neoplasms revealed staining with anti-GD3 (14/14, 31/31), anti-GM2 (9/14, 26/31), and anti-GD2 (6/14, 24/30), respectively. 3'-isoLM1 and 3',6' isoLD1, which exhibit a restricted oncofetal expression pattern and are not detectable in adult human brain, are present in 15/31 primary CNS neoplasms and in 1/8 human glioma xenografts, as detected by MAbs SL-50 and DMAb-14, respectively. EGFR proteins, the second target, have unique amino acid spans resulting from gene deletion in the amplified EGFR gene present in subsets of malignant human gliomas. Antibodies against EGFR deletion-mutant Type III show highly restricted activity with a subset of glioma biopsies (6/35) expressing the mutant EGFR. These reagents should be useful for in vitro and in vivo diagnosis and, potentially, for treatment of malignant brain tumors.
Mol Chem Neuropathol 1992 Oct
PMID:Monoclonal antibodies to malignant human gliomas. 138 25

Using homologous probes for the cloning of related genes within the family of guanine nucleotide-binding protein-coupled receptors, we have cloned the gene for the rhesus macaque D1 dopamine receptor. By using the rat D1 receptor coding sequence as a probe under high stringency conditions, the rhesus D1 receptor gene was isolated from a lambda EMBL3 rhesus genomic DNA library. The rhesus D1 dopamine receptor gene is intronless and encodes a 446-amino acid protein that contains two consensus sites for asparagine-linked glycosylation (Asn-5 and Asn-176) and two consensus sites for cAMP-dependent protein kinase phosphorylation (Thr-136 and Thr-268). The primary amino acid sequence of the rhesus D1 dopamine receptor shows an extremely high degree of similarity (99.6%) to the human D1 receptor. Genomic DNA analyses conducted with high and reduced stringency hybridizations indicate that the rhesus macaque D1 receptor is a member of a large multigene family. Like the human D1 receptor mRNA, the rhesus D1 receptor mRNA is approximately 4 kilobases in size and is localized predominantly in the caudate, with lesser amounts in the hippocampus and cortex. The rhesus D1 receptor coding region was inserted into the cytomegalovirus promoter-driven expression vector pcDNA-1, and the recombinant (pcDNA-D1) was cotransfected with the selectable marker pRSVneo, conferring G418 resistance, into D1 receptor-deficient C6 glioma cells. Analyses of the selected transfectant demonstrate the expression of a high affinity, functional D1 dopamine receptor. The D1 receptor radioligand [3H]SCH 23390 bound transfectant membranes with an affinity (Kd), of 0.3 nM; the D2-selective ligand spiperone, the dopamine receptor ligand clozapine, and the serotonin receptor antagonist ketanserin bound with considerably lower affinities (102, 80, and 95 nM, respectively). Both dopamine and the D1-selective agonist SKF 38393 inhibited the binding of [3H]SCH 23390 to transfectant cell membranes; the binding of these agonists was sensitive to GTP. Dopamine potently stimulated the accumulation of cAMP in transfected C6 cells, whereas SKF 38393 was a partial agonist in these cells. Also, the density of recombinant D1 receptors on the transfectant cells was decreased 40% upon treatment with 10 microM dopamine, indicating that occupation of recombinant D1 receptors by agonists alters surface expression of the receptors.
Mol Pharmacol 1992 Apr
PMID:Molecular cloning and expression of the rhesus macaque D1 dopamine receptor gene. 153 68

Glial fibrillary acidic protein (GFAP) is a 49 kDa component of 8 nanometers glial intermediate filaments. It is a definitive marker of both neoplastic and non-neoplastic glial cells. Malignant gliomas are heterogeneous in their structure and their expression of GFAP. Subjective visual impression of glioma cell cultures in early passage after explantation suggested two types of heterogeneity among the cells: 1) Indirect anti-GFAP immunofluorescence (IF) signal intensity appeared to vary among cells. 2). Sizes and shapes of cells appeared to vary. While many cultures lost GFAP+ cells by passage 2, some retained sufficient cells for study. Computerized microdensitometry and image analysis precisely assessed signal intensity, size and shape of glial cells from these latter cultures in passage 2 of cell culture. A Zeiss ICM 405 epi-illuminated fluorescent microscope with photographic interface to a Bio-Quant computerized microdensitometer measured IF signal intensity for GFAP. Normalized to the most intense reactivity, the mean intensity of GFAP expression of 26 glioma cells was 66.2%. The range of 5.2% to 100% around this mean reflected a high degree of heterogeneity of expression of GFAP by these cells. The effects of quenching of the fluorescent signal by the excitation beam were minimized in the following manner: a) Rhodamine anti-GFAP was substituted for more labile fluoresceine. b) A fluorescent filter and lens combination was selected to provide a high signal to quench ratio. c) The signal acquisition time was minimized and fixed to one standard interval. The image analysis system employed the described optics and computer.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Mol Biol 1992 Apr
PMID:Computerized image analysis of distinct cell marker parameters of glial fibrillary acidic protein: intensity of immunofluorescence and topography in human glioma cultures. 157 46


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