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)

1-Nitroso-2-naphthol reacts with various 5-hydroxyindoles as well as para-substituted phenols and guaiacols. Consequently, this reaction has long been used to measure tyrosine in tyrosinosis and tyrosinemia, homovanillic acid in neuroblastoma, and 5-hydroxy-3-indoleacetic acid in the carcinoid tumor. We report here on the specificity of this reaction, as well as our early observations with respect to the chemical basis of the reaction.
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PMID:The chemical basis and specificity of the nitrosonaphthol reaction. 619 18

A dimeric pentapeptide enkephalin (DPE2) consisting of two molecules of [D-Ala 2, Leu 5] enkephalin linked at C-terminal leucine with ethylenediamine, (H-Tyr-D-Ala-Gly-Phe-Leu-NH-Ch2)2 is a bivalent ligand for the delta enkephalin receptors of rat brain and neuroblastoma-glioma hybrid (NG108-15) cells. This new enkephalin analog shows dramatically increased affinity in radioligand assays using whole brain membranes when delta but not mu specific radioligands are employed. When membranes from NG108-15 cells are used, the dimer shows greatly increased activity irrespective of the mu or delta specificity of the tracer. The dimer DPE2 shows a four-fold, "sodium shift" in its IC50 for competition with [3H]naloxone, suggestive of agonist behavior. Agonist activity was confirmed by demonstrating that DPE2 inhibits cyclic AMP production in prostaglandin E1 stimulated NG108-15 cells, and by demonstrating very high potency in the mouse vas deferens bioassay. DPE2 binds to the same delta sites as the delta-selective monomer [D-Ala2, D-Leu5] enkephalin, since the two ligands show complete crossdisplacement. Radiolabeled 3H-DPE2 shows a five-fold higher affinity constant, a 2.5-fold higher association rate constant, and a two-fold lower dissociation rate than the monomer. These results are consistent with the hypothesis that the dimeric pentapeptide enkephalin can bridge two delta receptors. This enkephalin dimer provides a valuable new probe of opiate receptors and their organization in cell membranes.
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PMID:Dimeric pentapeptide enkephalin: a novel probe of delta opiate receptors. 629 43

Exorphins, peptides with opioid activity, have previously been isolated from pepsin hydrolysates of alpha-casein [Zioudrou, C., Streaty, R. A., & Klee, W. A. (1979) J. Biol. Chem. 254, 2446-2449]. Analysis of these peptides shows that they correspond to the sequences 90-96, Arg-Tyr-Leu-Gly-Tyr-Leu-Glu, and 90-95, Arg-Tyr-Leu-Gly-Tyr-Leu, of alpha-casein. These peptides, as well as two of their analogues Tyr-Leu-Gly-Tyr-Leu-Glu (91-96) and Tyr-Leu-Gly-Tyr-Leu (91-95), have now been synthesized and characterized. Their opioid activity was examined by three different bioassays: (a) displacement of D-2-alanyl[tyrosyl-3,5-3H]enkephalin-(5-L-methioninamide) and [3H]dihydromorphine from rat brain membranes; (b) naloxone-reversible inhibition of adenylate cyclase in homogenates of neuroblastoma x glioma hybrid cells; (c) naloxone-reversible inhibition of electrically stimulated contractions of the mouse vas deferens. The synthetic peptide of sequence 90-96 was the most potent opioid in all three bioassays and its potency was similar to that of the isolated alpha-casein exorphins. The synthetic peptides were totally resistant to hydrolysis by trypsin and homogenates of rat brain membranes, but were partially inactivated by chymotrypsin and subtilisin. The difference in opioid activity of alpha-casein exorphins may be related to differences in conformational flexibility observed by NMR spectroscopy.
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PMID:Opioid activities and structures of alpha-casein-derived exorphins. 631 43

Degradation of tritiated [Leu5]enkephalin was studied in cultures of neuroblastoma cells (clone N1E-115). Incubation of cells in suspension revealed Tyr as the main tritiated metabolite; however, Tyr-Gly-Gly and Tyr-Gly were detectable as well. In a crude membrane preparation of the neuroblastoma cells the level of Tyr is reduced to 13% and that of Tyr-Gly to 10% of the initial value, whereas Tyr-Gly-Gly is increased to about 5 times the initial value. Of the degraded enkephalin, 66% was accounted for by the formation of Tyr, 30% by the formation of Tyr-Gly-Gly and 4% by the formation of Tyr-Gly. The production of Tyr was inhibited by bestatin, an inhibitor of aminopeptidases, and that of Tyr-Gly-Gly by captopril, an inhibitor of angiotensin-converting-enzyme. The results prove the ability of neuroblastoma cells (N1E-115) to degrade enkephalin by aminopeptidase and the membrane-bound angiotensin-converting-enzyme.
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PMID:Enkephalin degradation by enkephalinergic neuroblastoma cells. Involvement of angiotensin-converting-enzyme. 632 31

Since there is no nutritional requirement for the biopterin cofactor, we attempted to create a drug-induced deficiency in rats in order to study the role of tetrahydrobiopterin in regulating the biosynthesis of dopamine and serotonin. The hypothesis that dihydrofolate reductase (EC 1.5.1.3) mediates the final step in the de novo synthesis of tetrahydrobiopterin was tested by treating rats with methotrexate along with leucovorin as a protective agent; there was no reduction in total biopterin or in the fraction present as tetrahydrobiopterin in adrenal medulla, adrenal cortex, pituitary, brain, or pineal glands. Similar results were obtained with metoprine, a lipid-soluble inhibitor of dihydrofolate reductase which readily enters the central nervous system. Treatment with loading doses of phenylalanine along with methotrexate reduced the level of tetrahydrobiopterin in liver. Neuroblastoma N115 cells growing in medium supplemented with thymidine and hypoxanthine continued to form normal amounts of tetrahydrobiopterin in the presence of concentrations of methotrexate which completely inhibited dihydrofolate reductase; higher concentrations of methotrexate increased the tetrahydrobiopterin content of the cells 2-fold and the total biopterin in the medium 3-fold. Although attempts to create a drug-induced deficiency were unsuccessful, the evidence indicates that the de novo synthesis of tetrahydrobiopterin proceeds by a pathway independent of dihydrofolate reductase and that folate antagonists, such as methotrexate are unlikely to impair the hydroxylation of tyrosine and tryptophan, which is dependent upon the availability of the biopterin cofactor.
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PMID:Biosynthesis of tetrahydrobiopterin in the presence of dihydrofolate reductase inhibitors. 686 19

The aim of this work was to study the selective modification of tryptophan residues with NBS. To accomplish this, a specific method to determine tryptophan was required initially. NBS reacts with both tryptophan and tyrosine residues, which are found in most enzyme proteins, and static spectrophotometric observation, which is usually employed to follow the progress of modification, is not selective for tryptophan. However, discrimination of tryptophan from tyrosine was achieved by the kinetic method with a stoppeed-flow apparatus. The rate of modification of tryptophan residues is 10(3) times larger than that of tyrosine, so rapid stopping of the reaction of NBS brings about the selective modification of tryptophan residues. Using fluorescence-spectrophotometric and kinetic methods, the modification with NBS of model compounds of the tryptophan residue could be simply followed as a single phase, even though the reaction is complex when followed by the static spectrophotometric method.
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PMID:Stopped-flow studies on the chemical modification with N-bromosuccinimide of model compounds of tryptophan residues. 735 35

We have developed a routine capillary gas-chromatographic profiling method for simultaneous quantitative determination of the tert-butyldimethylsilyl derivatives of homovanillic acid, vanilmandelic acid, 3-methoxy-4-hydroxyphenylethylene glycol, and 3,4-dihydroxyphenylacetic acid and the estimation of 5-hydroxyindole-3-acetic acid in urine. The method is useful for diagnosis and followup of patients with functional tumors characterized by increased urinary excretion of metabolites originating from the metabolism of tyrosine and tryptophan--e.g., neuroblastoma, pheochromocytoma, carcinoid, and melanoma. It may also be applicable in pharmacokinetic studies of administered aromatic amino acids (parkinsonism, mental diseases, loading tests) and for diagnosis and followup of patients with inborn errors of metabolism that are characterized by organic aciduria (for instance, tyrosyluria and phenylketonuria).
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PMID:Simultaneous determination of the four major catecholamine metabolites and estimation of a serotonin metabolite in urine by capillary gas chromatography of their tert-butyldimethylsilyl derivatives. 746 Feb 71

Steady-state levels of gp140proto-trk in cell lines and tumor tissues of neuroblastoma were examined by immunoblotting with anti-gp140proto-trk. The level of gp140proto-trk varied but showed good correlations with the stage of the tumor and the age of the patients at the time of diagnosis. Moreover, patients with higher expression of gp140proto-trk clearly had a far better survival rate than those with lower expression, suggesting that suppression of gp140proto-trk strongly correlates with the malignant conversion of the tumor. However, we found that neither autophosphorylation of gp140proto-trk nor tyrosine phosphorylation of cellular proteins was elevated in tumors of the higher expression group. These results suggest that gp140proto-trk does not actively participate in the process of transformation or the suppression of malignant conversion. Rather, the higher level of gp140proto-trk may reflect the greater level of differentiation of tumor cells.
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PMID:Abundant but inactive-state gp140proto-trk is expressed in neuroblastomas of patients with good prognosis. 750 4

We show here that a protein tyrosine phosphatase inhibitor, sodium orthovanadate, induces rat pheochromocytoma cells to express neurites, a prominent morphological marker of neuronal phenotype. Vanadate-induced differentiation and neurite outgrowth in pheochromocytoma cells was not as extensive as that induced by the positive control employed, nerve growth factor. However, neurite outgrowth responses were comparable between nerve growth factor-treated pheochromocytoma cells and cells primed and then restimulated with vanadate. In the human neuroblastoma cell line, SH-SY5Y, a single exposure to vanadate induced neurite extension in this cell line equal to that initiated by nerve growth factor. In both cell lines vanadate treatment resulted in tyrosine phosphorylation of several high-molecular-weight proteins and using anti-phosphotyrosine antibodies, intense fluorescence was observed in the cell body and neurites of pheochromocytoma cells exposed to vanadate. Vanadate mediated differentiation and neurite outgrowth in pheochromocytoma cells could be ablated by the tyrosine kinase inhibitor erbastatin, whereas nerve growth factor-induced neurite outgrowth was only partially inhibited. In SH-SY5Y cells, erbstatin mediated partial inhibition of both vanadate and nerve growth factor-induced neurite elongation with similar kinetics. In contrast, K252b, a trk tyrosine kinase inhibitor, exhibited only a 30% reduction of neurite outgrowth in vanadate treated pheochromocytoma cells but an 80% reduction in nerve growth factor-treated cells. In SH-SY5Y cells, K252a did not have a statistically significant effect on neurite elongation induced by vanadate in contrast to a 60% reduction in nerve growth factor-treated cells. The membrane impermeable analogue K252b, had no effect on neurite elongation induced with either vanadate or nerve growth factor in these cells. The effects of vanadate were not mimicked by ouabain (0.1-50 microM) indicating that vanadate does not induce differentiation and/or neurite extension by inhibiting ion channel Na,K-ATPase, which is one of its other well-characterised inhibitory activities. Evidence for the selective action of vanadate on some but not all neuronal cell lines comes from the fact that it did not induce neurite extension in the human neuroblastoma cell line SK-N-MC. These data imply that vanadate-induced neurite outgrowth responses in pheochromocytoma and SH-SY5Y cells can be induced by the inhibition of tyrosine phosphatases and appears not to simply mimic nerve growth factor signals. The target(s) of vanadate action in the two cell lines are currently being sought.
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PMID:Vanadate stimulates differentiation and neurite outgrowth in rat pheochromocytoma PC12 cells and neurite extension in human neuroblastoma SH-SY5Y cells. 752 Oct 24

The cytokines leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) have been implicated in determination of neuronal phenotype as well as promotion of neuronal survival. However, the intracellular mechanisms by which their signals are transduced remain poorly understood. We have previously studied the regulation of vasoactive intestinal polypeptide gene expression by LIF and CNTF in the NBFL neuroblastoma cell line. Because these cytokines induce tyrosine phosphorylation that may lead to Ras activation, we explored a possible role for Ras in LIF- and CNTF-induced signal transduction. In NBFL cells LIF increases activated Ras in a rapid, transient, and concentration-dependent manner. CNTF and a related cytokine, oncostatin M, produce similar increases. CNTF and LIF also increase activated Ras in neuron-enriched dissociated cultures of sympathetic ganglia. Moreover, these cytokines rapidly and transiently induce specific tyrosine-phosphorylated proteins, p165 and p195. The protein kinase inhibitors K252a and staurosporine block LIF-induced increases in tyrosine phosphorylation, activated Ras, and vasoactive intestinal polypeptide mRNA in NBFL cells. These data support a possible role for Ras in the cell differentiation effects of LIF and CNTF.
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PMID:Leukemia inhibitory factor and ciliary neurotrophic factor increase activated Ras in a neuroblastoma cell line and in sympathetic neuron cultures. 752 87


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