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)

Rubrophilin, a unique brain specific polypeptide, was purified to apparent homogeneity from microsomal fractions of bovine brains. The peptide stains pink with Coomassie Brilliant Blue R-250 (C.I. No. 42660) under specific conditions, has an apparent Mr of 53,000, and is acidic with an apparent pI of 4.9. The purification involves initial solubilization of delipidated microsomes in sodium dodecyl sulfate, followed by ammonium sulfate fractionation, reversed ammonium sulfate gradient elution from diatomaceous earth, gel filtration on polyacrylamide (Biogel P-200), gradient elution chromatography from hydroxylapatite, and reverse-phase chromatography from phenyl-Sepharose. A yield of about 5 mg of rubrophilin was obtained from 9 g of microsomal proteins. Amino acid analysis shows that rubrophilin contains only nine amino acids with residues/mol as follows: alanine (102), glutamic acid (97), lysine (65), proline (55), aspartic acid (48), glycine (44), serine (37), threonine (35), and valine (10). Cysteine, methionine, tryptophan, tyrosine, isoleucine, phenylalanine, histidine, and arginine could not be detected. Relative rubrophilin content of vertebrate brains was as follows: mammals greater than birds greater than reptiles greater than fishes. It is present in mouse retina and human neuroblastoma cell cultures but could not be detected in octopus optic lobe or in cultured C-6 rat glioma cells.
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PMID:Purification and properties of rubrophilin: a novel brain specific membrane polypeptide. 380 7

The nuclear protein kinase NI (NI kinase) was purified from NB-15 mouse neuroblastoma cells by phosphocellulose column and casein affinity column chromatography. The purified NI kinase exhibited (i) an apparent subunit molecular weight of about 37,000, (ii) autophosphorylation, and (iii) insensitivity to inhibition by heparin. When NI kinase was added to heat-treated neuroblastoma nuclei in the presence of [gamma-32P] ATP, two proteins with apparent subunit molecular weights of 11,000 and 10,000 were prominently phosphorylated. Other protein kinases tested including the nuclear protein kinase NII, Type I cAMP-dependent protein kinase, and protein kinase C did not catalyze the phosphorylation of these two proteins. The NI kinase-catalyzed phosphorylation of these two proteins was completely inhibited by 1 mM spermine. In contrast, 10 mM putrescine, 2 mM spermidine, 5 mM arginine, and 10 mM NH4Cl, had no inhibitory effect on this phosphorylation reaction. Our study also indicated that the phosphorylation of the 11,000- and 10,000-dalton proteins occurred in the nuclear matrix fraction but not in heterogeneous nuclear ribonucleoproteins, high mobility group proteins, or histone fractions. We have previously reported that spermine specifically inhibits the endogenous phosphorylation of an 11,000-dalton nuclear protein in various mammalian cell lines (Chen, K. Y., and Verma, R. (1984) Biochem. Biophys. Res. Commun. 118, 710-716). The present study suggests that the 11,000- and 10,000-dalton nuclear proteins may be native substrates of nuclear protein kinase NI and that their phosphorylation can be affected by physiological concentrations of spermine.
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PMID:Spermine inhibits the phosphorylation of the 11,000- and 10,000-dalton nuclear proteins catalyzed by nuclear protein kinase NI in NB-15 mouse neuroblastoma cells. 394 52

Guanylate cyclase in neuroblastoma N1E 115 cells was readily solubilized upon homogenization of the cells with hypotonic buffer. When the supernatant was passed through cation exchangers such as a Chelex 100 Na+ column, the guanylate cyclase activity in the effluent fraction decreased to 4-6% of the original supernatant. The addition of the acid extract of neuroblastoma cells or rat tissues to the effluent restored guanylate cyclase activity, indicating that the supernatant of neuroblastoma cells contained an acid-soluble endogenous activator for guanylate cyclase which was adsorbed on cation exchangers. The activator was purified from rat brain and identified as L-arginine by 13C- and 1H-NMR spectroscopy and paper partition chromatography. L-Arginine, at a concentration of 1-2 x 10(-5) M, stimulated guanylate cyclase activity in the effluent fraction 15-25-fold, whereas D-arginine and other basic L-amino acids were ineffective. Peptides that contained L-arginine at the NH2- or COOH-terminal also resulted in an activation of guanylate cyclase to the extent similar to that of L-arginine, while peptides that contained L-arginine inside the peptide chain failed to stimulate the activity. The activation of L-arginine seemed to operate by a mechanism similar to that induced by nitroso compounds.
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PMID:L-Arginine identified as an endogenous activator for soluble guanylate cyclase from neuroblastoma cells. 612 10

Intracellular cyclic GMP content responds to the stimulation of muscarinic receptor in a variety of tissues. Several aspects of the cellular mechanism involved in the synthesis of cyclic GMP were investigated. 1. In cultured bovine chromaffin cells, acetylcholine as well as muscarine stimulated the 32Pi incorporation into phosphatidic acid, induced Ca2+ mobilization across the cells, and, in parallel, elevated intracellular cyclic GMP content. Phosphatidic acid added to culture medium also stimulated the efflux and influx of Ca2+ and the synthesis of cyclic GMP in bovine chromaffin cells and in neuroblastoma cells in the same fashion as acetylcholine. 2. We have succeeded in a purification of an endogenous activator for guanylate cyclase from rat brain and identified it as L-arginine. L-Arginine, but not D-arginine, activated soluble guanylate cyclase 10- to 20-fold at a low concentration (1-2 X 10(-5) M). The activation of the enzyme by L-arginine seemed to require Ca2+. Calcium accumulated in cells in response to muscarinic stimulation would activate guanylate cyclase in collaboration with L-arginine. 3. Using a specific monoclonal antibody, we demonstrated the cellular and subcellular localizations of guanylate cyclase in rat brain. An intense reaction was observed in the brain regions which were rich in muscarinic receptor. Electron microscopic examination revealed that guanylate cyclase was concentrated in the postsynaptic perikaryon and dendrites of some type of neurons indicating its involvement in neural transmission.
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PMID:Cellular mechanism involved in the synthesis of cyclic GMP in nervous tissues. 613 49

Pertussis toxin (islet-activating protein) activates adenylate cyclase in susceptible cells by ADP-ribosylating an inhibitory component of the cyclase system. This toxin, assayed in a cell-free system in the presence of high concentrations of thiol, catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. This NAD glycohydrolase activity co-chromatographed on Sephacryl G-200 in 6.5 M urea, pH 3.2, 0.1 M glycine with the ADP-ribosyltransferase activity of the toxin, as monitored by the transfer of [32P]ADP-ribose from [32P]NAD to a 41,000-Da protein in NG108-15 neuroblastoma X glioma hybrid cells. In the absence of thiol, the native holotoxin was enzymatically inactive. Following addition of 250 mM dithiothreitol to the assay, maximal enzymatic activity was evident after a delay of approximately 1 h; with 20 mM thiol, the delay was longer. The Km for NAD with the fully activated enzyme was 25 microM; the Km did not appear to vary with the extent of activation. Thiol was necessary in a cell-free system to demonstrate NAD glycohydrolase activity. When extensively washed membranes were used as a source of 41,000-Da substrate, thiol was necessary to observe ADP-ribosylation in some cases (human erythrocytes) and significantly stimulated activity in others (NG108-15 cells). In contrast to the bacterial toxins choleragen and Escherichia coli heat-labile enterotoxin that ADP-ribosylate stimulatory components of the cyclase system, pertussis toxin did not transfer ADP-ribose to low molecular weight guanidino compounds, such as arginine or agmatine.
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PMID:Activation by thiol of the latent NAD glycohydrolase and ADP-ribosyltransferase activities of Bordetella pertussis toxin (islet-activating protein). 631 27

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

Human retinoblastoma contains clusters of cells immunoreactive for methionine-enkephalin and methionine-enkephalin-arginine-phenylalanine. Some tumour cells also exhibited methionine-enkephalin-arginine-glycine-leucine-like immunoreactivity. The results are in agreement with those obtained with similar testing of neuroblastoma cell cultures. It is concluded that some human retinoblastoma cells are capable of synthesizing preproenkephalin A or parts of this molecule.
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PMID:Immunohistochemical evidence for preproenkephalin A synthesis in human retinoblastoma. 638 22

The effect of polyamines (putrescine, spermidine and spermine) on endogenous protein phosphorylation in mouse neuroblastoma cells was investigated by using techniques of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The results indicated that spermine at 1mM completely inhibited the phosphorylation of the 11,000-dalton and 120,000-dalton proteins in nuclear fractions. The inhibition of the phosphorylation of the 11,000-dalton but not the 120,000-dalton protein by spermine was also observed in five other cell lines examined and appeared to be a general phenomenon. The inhibitory effect of spermine on the phosphorylation of the 11,000-dalton protein was specific, other cations such as ammonium chloride, arginine, putrescine, cyclen and trien were ineffective at equal molar or much higher concentrations.
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PMID:Spermine specifically inhibits the phosphorylation of an 11,000-dalton nuclear protein in various cultured mammalian cell lines. 670 3

The coupling of m5 muscarinic acetylcholine receptors to the generation and release of nitric oxide (NO) was investigated. Chinese hamster ovary cells, which stably express m5 receptors, were transiently transfected with the gene encoding neuronal NO synthase and used as a model system. Increased generation of NO upon stimulation of cells by muscarinic agonists was detected by an increase in cyclic GMP in admixed mouse neuroblastoma N1E-115 cells or more directly by measuring the conversion of L-arginine into L-citrulline. Carbachol increased cyclic GMP formation in the mixture of cells in a time- and concentration-dependent manner, with a half-maximal response occurring in the nanomolar range. This response was significantly attenuated by scavengers of NO or inhibitors of NO synthase. This high potency of carbachol was also observed in measurements of L-citrulline formation. A series of muscarinic agonists were as efficacious as carbachol in stimulating NO synthase, whereas McN-A-343 and pilocarpine were partial agonists in this regard. Evidence for an exceptionally high efficiency of coupling of m5 receptors to this response and its possible implication in the interaction between cholinergic and dopaminergic neurotransmission is discussed.
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PMID:Efficient coupling of m5 muscarinic acetylcholine receptors to activation of nitric oxide synthase. 750 88

Cell-adhesion activity of the bovine propolypeptide of von Willebrand factor (pp-vWF) was assessed by means of an in vitro assay with several cell lines of both normal and tumor-cell origin. pp-vWF promoted adhesion and spreading of B16 mouse melanoma cells and G-361 human melanoma cells. However, it could not induce adhesion of any other cell lines tested including endothelial cells, normal fibroblasts, and tumor cells of sarcoma, carcinoma, neuroblastoma and leukemia origin. A monospecific polyclonal antibody against pp-vWF, but not against fibronectin, laminin, and von Willebrand factor (vWF), completely blocked the pp-vWF-mediated adhesion, indicating that the cell adhesion was due to the pp-vWF molecule and not due to possible contamination of these three well-known adhesive proteins. The cell-adhesion activity was also observed with human pp-vWF and, furthermore, the adhesion to both bovine and human pp-vWF was not affected by a peptide containing the Arg-Gly-Asp sequence while the peptide abolished the cell adhesion to vWF. The adhesion was completely dependent on Mg2+ and inhibited by Ca2+. Inhibition by an anti-(beta 1 integrin) mAb (4B4) indicates that the receptor for this protein belongs to the beta 1-integrin family. A monoclonal antibody (TC4) among several antibodies directed against bovine pp-vWF inhibited the B16 adhesion to immobilized pp-vWF. The epitope for this monoclonal antibody lies in a central 8-kDa portion of pp-vWF, suggesting that this region is important for the cell-adhesion activity. This idea was supported by the finding that purified 8-kDa fragment promoted adhesion of B16 cells in a concentration-dependent manner. As pp-vWF shows unique cell-type specificity in its adhesion activity, which is completely different from that of fibronectin, laminin, vWF and collagen, it may be a novel type of adhesive glycoprotein that utilizes a beta 1-integrin receptor.
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PMID:Beta 1-integrin-mediated adhesion of melanoma cells to the propolypeptide of von Willebrand factor. 751 67


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