Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Flat, amorphous astroblasts in culture differentiate into rounded process-bearing cells after removal of serum from the media or following addition of dibutyryl cyclic-AMP (dbcAMP). We report here that addition of thrombin (10 nM) to rat primary astroglial cultures reversed both the spontaneous morphological differentiation of astroblasts caused by serum removal, and the more extensive morphological differentiation caused by pre-treatment with dbcAMP. The astroblasts retained the ability to differentiate upon removal of thrombin from the medium. Proteolytic activity of thrombin was required for the reversal of differentiation. Moreover, addition of serine protease inhibitors active against thrombin elicited a prolonged morphological differentiation rivaling that induced by dbcAMP, suggesting that inactivation of cell-associated thrombin might be sufficient for morphological differentiation to occur. Two other serine proteases with a cleavage specificity similar to thrombin were ineffective in reversing differentiation. Both the induction of morphological differentiation by dbcAMP and its reversal by thrombin were rapid, being essentially complete by 1 h. With more prolonged treatments, thrombin also reduced the dbcAMP-mediated increase in glutamine synthetase, a biochemical marker for astroglial differentiation. Thrombin also inhibited morphological differentiation in C6 glioma and altered the morphology of microglial cells; however, thrombin did not prevent neurite outgrowth in primary central neuronal cultures in contrast to its previously reported effects on the neuroblastoma 2a cell line. These findings indicate that a proteolytic mechanism mediated by thrombin and its inhibitors may underlie the regulation of astroglial differentiation.
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PMID:Thrombin and its inhibitors regulate morphological and biochemical differentiation of astrocytes in vitro. 197 84

Lead has been demonstrated to induce precocious glial differentiation both in vitro and in vivo. Lead-treated rat glioma (C6) and cerebellar astrocytes exhibited cytoplasmic extensions and the presence of glial endfeet after a 3-day exposure to 10(-6) to 10(-4) M PbCl2. In similar experiments no effect was noted in neuroblastoma (Neuro-2a) or on neurite outgrowth from chick spinal cord explants. This prodifferentiative effect on glia was also seen in the cerebella of postnatal rats in which the developmental expression of glial-specific glutamine synthetase activity was significantly increased up to postnatal day 12 after chronic exposure to lead from time of birth via their dam's drinking water (400 mg PbCl2/l).
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PMID:Chronic low level lead exposure precociously induces rat glial development in vitro and in vivo. 289 24

We report the isolation of a complimentary DNA (cDNA) clone encoding glutamine synthetase, derived from a population of methionine sulfoxime-resistant mouse GF1 fibroblasts. When GF1 cells are incubated for 48 h in the presence of the glucocorticoid hormone dexamethasone, the specific activity of glutamine synthetase (GS), assayed as glutamyltransferase activity, increases by threefold. Based on dot hybridization analysis, hormonal treatment also produces a similar increase in the level of GS mRNA. When GF1 cells or mouse Neuro 2A neuroblastoma cells are transferred from medium containing 4 mM glutamine to glutamine-free medium, glutamyltransferase activity increases by at least fivefold. However, the presence or absence or glutamine in the medium does not affect the relative level of glutamine synthetase mRNA in either cell line. With both GF1 and Neuro 2A cells, the half-time for the decline in glutamine synthetase enzyme activity on addition of glutamine to the medium is approximately 1.5 h. This rapid decline, coupled with the lack of effect of glutamine on the level of GS messenger RNA in Neuro 2A cells, renders it unlikely that neural cells alter glutamine synthetase levels in response to glutamine by a biosynthetic mechanism, as suggested by previous authors [L. Lacoste, K.D. Chaudhary, and J. Lapointe (1982) J. Neurochem. 39, 78-85].
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PMID:Multiple mechanisms by which glutamine synthetase levels are controlled in murine tissue culture cells. 290 21

Regulation of the biosynthesis of glutamine synthetase was studied in neuroblastoma cells (Neuro-2A) by use of a recently developed, sensitive radioisotopic assay. The removal of glutamine from the culture medium of these cells for 24 h resulted in a 10-fold increase in glutamine synthetase specific activity (15-fold after 2 weeks) compared with the basal level found in cells grown in the presence of 2 mM glutamine. Following the growth of these cells for 2 weeks in the presence of various concentrations of glutamine, a negative linear correlation was observed between the specific activity of glutamine synthetase (from 1.7 to 0.14 unit/mg) and the concentration of glutamine in the growth medium (from 0.5 to 2 mM). Cycloheximide or actinomycin D blocked the increase in glutamine synthetase activity observed in the absence of glutamine. These results suggest that the removal of glutamine led to the induction of glutamine synthetase by stimulating new enzyme synthesis. The enzyme was not degraded, but only diluted, by growth upon readdition of glutamine to the medium. The influence of glutamine depletion is also reported for C-6 glioma cells and glial cells in primary cultures.
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PMID:Derepression of the glutamine synthetase in neuroblastoma cells at low concentrations of glutamine. 612 53

A sensitive method for assaying glutamine synthetase activity is described. This enzyme produces ?-glutamylhydroxamate in the presence of l-glutamic acid and hydroxylamine as substrates. This amino acid hydroxamate was separated and quantified by high performance liquid chromatography on an ion-exchange resin column using post-column derivatization with o-phthalaldehyde for detection. As little as 50 pmol of ?-glutamylhydroxamate was detected in assays using cell-free extracts from fish retina, rat clonal C6 glioma cells, mouse clonal NIE 115 and N18TG2 neuroblastoma cells, whose specific activity measured was 1.0, 0.03, 0.01 and 0.01 ?mol of ?-glutamylhydroxamate produced per 30 min per milligram protein, respectively.
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PMID:A high performance liquid chromatography assay for glutamine synthetase. 2050 55