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)

Some neuron-derived cells, such as neuroblastoma cells, adhere and extend neurites on fibronectin (FN) substrata by processes that can be independent of binding to the Arg-Gly-Asp-Ser sequence (RGDS in FN) and independent of proteoglycan/ganglioside-binding activities of FN. Proteolytic fragments of various FNs have been used in this study to map a new adhesion-promoting domain in FNs that may be neural cell-specific. A thermolysin-generated fragment of human plasma FN (F110 containing the RGDS domain) or the analagous fragment from transformed human cell FN (F120, also containing the alternately spliced extra domain b[EDb]) facilitate RGDS-independent adherence and neurite extension of human neuroblastoma cells and an F11 hybrid neuronal line (by fusion of mouse neuroblastoma cells with rat dorsal root ganglion neurons) as effectively as adherence and neurite extension on intact FN. Since neither F110 nor F120 contains sequences from the alternately spliced IIICS region of FN, neurite-promoting activity in these fragments cannot be ascribed to a recently discovered cell-binding domain in this region. Furthermore, F120 could be cleaved into two subfragments retaining virtually all the sequence of the parent fragment: F35 from the C terminus of F120 containing the RGDS domain, and F90 from the N terminus containing most of the EDb region bordering the thermolysin cleavage site. These neuronal cells could adhere but not extend neurites on substrata coated with either F35 or F90 alone while 3T3 cells could adhere only on F35. Mixtures of F35 and F90 on substrata could reconstitute some, but not nearly all, of the neurite-promoting activity of F120. Therefore, these data identify a new cell-binding domain in common sequences of FNs on the N-terminal side of EDb and demonstrate cooperativity between this RGDS-independent domain and the RGDS-dependent domain for maximal differentiation of these neuron-derived cells. Several possibilities for a receptor directed to this new domain are discussed.
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PMID:Requirement for two different cell-binding domains in fibronectin for neurite extension of neuronal derivative cells. 235 3

Stimulation of soluble guanylyl cyclase in rat fetal lung fibroblasts (RFL-6 cells) was used as a sensitive assay for endothelium-derived relaxing factor/nitric oxide (EDRF/NO) formation. Intact N1E-115 cells released an EDRF/NO-like material that enhanced cyclic GMP levels in RFL-6 cells. The synthesis of this substance could be stimulated with the receptor agonist neurotensin (10 microM) or by addition of the EDRF/NO substrate L-arginine (100 microM). In Ca2(+)-free Locke's solution, stimulation of EDRF/NO production by both neurotensin and L-arginine was abolished. The EDRF/NO-synthesizing activity was localized in the cytosol of N1E-115 cells. The activity was lost after boiling and it was highly sensitive to Ca2+ with the major increase in activity occurring between 100 and 500 nM Ca2+. L-Arginine and NADPH were required for maximal synthesis of EDRF/NO by the enzyme(s). The synthesis of EDRF/NO was inhibited by the following antagonists of calmodulin-regulated functions (with the approximate IC50 values given in parentheses): calmidazolium (7 microM), trifluoperazine (10 microM), fendiline (80 microM), W-7 (N-[6-aminohexyl]-5-chloro-1-naphthalenesulfonamide) (120 microM), and compound 48/80 (3 micrograms/ml). The EDRF/NO-synthesizing activity was partially purified from N1E-115 cytosol by DE 52 anion exchange chromatography. The activity was eluted with 0.1 M KCl. The enzyme(s) showed very little activity in the presence of L-arginine (100 microM) and NADPH (100 microM), but the activity could be fully restored by addition of exogenous calmodulin (EC50, approximately 2 units/ml). At 0.3 M KCl, a fraction eluted from the DE 52 column that was also able to fully restore the EDRF/NO-synthesizing activity. Thus, this fraction is likely to contain the endogenous Ca2(+)-binding protein. It is concluded that the activity of the EDRF/NO-synthesizing enzyme(s) in N1E-115 neuroblastoma cells is regulated by Ca2+ and calmodulin.
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PMID:Hormone-induced biosynthesis of endothelium-derived relaxing factor/nitric oxide-like material in N1E-115 neuroblastoma cells requires calcium and calmodulin. 237 Aug 55

Substance P at micromolar concentrations enhances the uptake of [14C]guanidinium in neuroblastoma X glioma hybrid cells, an effect which most likely indicates activation of Na+ permeability. The substance P receptor was characterized pharmacologically. Analogues of substance P with D-amino acids e.g. spantide, and substance P-methyl ester were similarly active. Substance P (free acid), fragments of the substance P precursor, and substance P-(1-9) displayed no activity. This indicates the importance of the hydrophobic C-terminal for stimulation of the hybrid cells. The potency was reduced with decreasing length the of C-terminal fragments. However, the substance P antagonists [D-Pro4,D-Trp7,9,Nle11]substance P-(4-11) and [D-Pro4,D-Trp7,9,10]substance P-(4-11) showed substantially greater activity than substance P-(4-11). Substance P-(6-11) (i.e. H-Arg-DTrp-MePhe-DTrp-Leu-Met-NH2) behaved as a mixed agonist-antagonist. At concentrations higher than 10 microM, it inhibited the stimulation exerted by substance P. No other peptides of the tachykinin family (neurokinins A and B, physalaemin, eledoisin, kassinin) nor the synthetic analogues with specificity for certain receptor subtypes ([pGlu6,Pro9]substance P-(6-11), DiMe-C7, i.e. [pGlu5,MePhe8,Sar9]substance P-(5-11) and senktide, i.e. N-succinyl-[Asp6,MePhe8]substance P-(6-11) had any effect on guanidinium uptake in the hybrid cells. Hence, the substance P site with low affinity on the hybrid cells does not fit into the usual classification of tachykinin receptors but resembles the site that modulates nicotinic acetylcholine receptors on chromaffin cells.
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PMID:Characterization of a substance P receptor activating a cation permeability in neuronal cell lines. 245 Jul 63

A membrane-bound adhesive protein that promotes neurite outgrowth in brain neurons has been isolated from rat brain (Rauvala, H., and R. Pihlaskari. 1987. J. Biol. Chem. 262:16625-16635). The protein is an immunochemically distinct molecule with a subunit size of approximately 30 kD (p30). p30 is an abundant protein in perinatal rat brain, but its content decreases rapidly after birth. In the present study the amino-terminal sequence of p30 was determined by automated Edman degradations. A single amino-terminal sequence was found, which is not present in previously studied adhesive molecules. This unique sequence has a cluster of five positive charges within the first 11 amino acid residues: Gly-Lys-Gly-Asp-Pro-Lys-Lys-Pro-Arg-Gly-Lys. Antisynthetic peptide antibodies that recognize this sequence were produced in a rabbit, purified with a peptide affinity column, and shown to bind specifically to p30. The antipeptide antibodies were used, together with anti-p30 antibodies, to study the localization of p30 in brain cells and in neuroblastoma cells as follows. (a) Immunofluorescence and immunoelectron microscopy indicated that p30 is a component of neurons in mixed cultures of brain cells. The neurons and the neuroblastoma cells expressed p30 at their surface in the cell bodies and the neurites. In the neurites p30 was found especially in the adhesive distal tips of the processes. In addition the protein was detected in ribosomal particles and in intracellular membranes in a proportion of cells. (b) The antibodies immobilized on microtiter wells enhanced adhesion and neurite growth indicating that p30 is surface exposed in adhering neural cells. (c) Immunoblotting showed that p30 is extracted from suspended cells by heparin suggesting that a heparin-like structure is required for the binding of p30 to the neuronal cell surface. A model summarizing the suggested interactions of p30 in cell adhesion and neurite growth is presented.
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PMID:The adhesive and neurite-promoting molecule p30: analysis of the amino-terminal sequence and production of antipeptide antibodies that detect p30 at the surface of neuroblastoma cells and of brain neurons. 246 49

Two dynorphin-degrading cysteine proteases, I and II, were extracted with Triton X-100 from neuroblastoma cell membrane, isolated from accompanying dynorphin-degrading trypsin-like enzyme by affinity chromatography on columns of soybean trypsin inhibitor-immobilized Sepharose and p-mercuribenzoate-Sepharose, and separated by ion-exchange chromatography on diethylaminoethyl (DEAE)-cellulose and TSK gel DEAE-5PW columns. Cysteine protease II was purified further by hydroxyapatite chromatography and gel filtration. The molecular weights of cysteine proteases I and II were estimated to be 100,000 and 70,000, respectively, by gel filtration. Both of the enzymes, were inhibited by p-chloromercuribenzoate, N-ethylmaleimide, and high-molecular-weight kininogen, but not or only slightly inhibited by diisopropylphosphorofluoridate, antipain, leupeptin, E-64, calpain inhibitor, and phosphoramidon. Cysteine protease I cleaved dynorphin(1-17) at the Arg6-Arg7 bond with the optimum pH of 8.0, whereas II cleaved dynorphin(1-17) at the Lys11-Leu12 bond and the Leu12-Lys13 bond with the optimum pH values of 8.0 and 6.0, respectively. These bonds corresponded to those that had been proposed as the initial sites of degradation by neuroblastoma cell membrane. Cysteine protease I was further found to show strict specificity toward the Arg-Arg doublet, when susceptibilities of various peptides containing paired basic residues were examined as substrates for the enzyme.
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PMID:Characterization of cysteine proteases functioning in degradation of dynorphin in neuroblastoma cells: evidence for the presence of a novel enzyme with strict specificity toward paired basic residues. 256 12

The cytosolic fraction of N1E-115 neuroblastoma cells catalysed the L-arginine- and NADPH-dependent formation of a substance that relaxed endothelium-denuded strips of rabbit aorta. Relaxations in response to this substance were enhanced in the presence of superoxide dismutase. N omega-Nitro-L-arginine and NG-monomethyl-L-arginine, two inhibitors of EDRF synthesis, markedly attenuated the relaxations. Hemoglobin, a scavenger of EDRF, and methylene blue, an inhibitor of soluble guanylate cyclase, completely abolished the relaxation to N1E-115 cytosol. In contrast, the cyclo-oxygenase inhibitor indomethacin did not alter the relaxations. These data demonstrate that the cytosol of a neuronally-derived cell line is able to synthesize a substance with pharmacological properties similar to EDRF.
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PMID:The cytosol of N1E-115 neuroblastoma cells synthesizes an EDRF-like substance that relaxes rabbit aorta. 263 48

Sixteen murine hybridoma-secreting monoclonal antibodies against pancreatic islet cell surface antigens (mc-ICSA) have been produced by the cell fusion technique using splenocytes from xenogeneic islet cell- or RIN cell-immunized Balb/c mice. In addition, some mice were autoimmunized by subdiabetogenic doses of the beta cell toxin streptozotocin in combination with complete Freund's adjuvant. Isotyping of the mc-ICSA revealed that 13 of the antibodies belong to the class IgM, and 3 to the subclass IgG1. The specificity of these mc-ICSA has been detected by means of the indirect immunofluorescent technique using primary rat islet cells suspensions, following a procedure of double immunostaining for pancreatic insulin and glucagon. Furthermore, the cross reactivity of these mc-ICSA was studied using endothelial, neuroblastoma and fibroblast cell lines and primary rat splenocytes. One out of the 10 mc-ICSA tested was alpha cell-specific, 2 were beta cell-specific and 7 out of 10 were reactive with both alpha and beta cells. Eleven mc-ICSA showed no cross-reactivity with the 5 other cell types tested. The binding of one mc-ICSA was blocked by 6 of the ICSA-positive human sera which were tested, suggesting that this monoclonal recognizes the same antigenic determinant. The same mc-ICSA diminished the glucose- and arginine-stimulated insulin secretion of isolated rat islets.
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PMID:Heterogeneity of monoclonal antibodies against pancreatic beta cells. 267 11

Very late antigen (VLA) 1 is a member of the family of integral plasma-membrane glycoproteins known as integrins. It is a heterodimer composed of an alpha subunit of Mr 200,000, noncovalently associated with a beta subunit of Mr 110,000 which is shared by other VLA molecules (VLA-2-5). Unlike most of the other VLA proteins which have been shown to be receptors for various extracellular matrix proteins, the ligand for VLA-1 is unknown. Utilizing polyclonal antisera against the human fibronectin receptor as well as alpha subunit-specific monoclonal antibodies and cDNA probes, we have been able to demonstrate that in two human neuroblastoma cell lines, IMR-32 and SK-N-SH, the common beta subunit is associated with alpha 1, alpha 2, alpha 3, and alpha 5 subunits. By culturing these two cell lines in the presence of a synthetic peptide, Gly-Arg-Gly-Asp-Ser-Pro, which contains the Arg-Gly-Asp cell attachment promotion tripeptide, we have isolated variant cell lines resistant to the detachment effects of this peptide. Peptide-resistant SK-N-SH and IMR-32 neuroblastoma cells exhibit weaker attachment to type I collagen and laminin, but a similar level of attachment to fibronectin as compared to the parental cells. Although the peptide-resistant variant cell lines proliferate at a rate similar to that of the parental cell lines, they stably overproduce (up to 20-fold) the alpha 1 subunit (VLA-1) specifically; and in the IMR-32 variant cells, the common beta 1 subunit is also overproduced. The level of expression of alpha 2 and alpha 3 subunits, however, is considerably reduced and that of the alpha 5 subunit is unchanged relative to the parental cells. These data suggest that the expression of integrin alpha subunits can be regulated differentially and independently of the beta subunit and that the VLA-1 heterodimer has an important function in mediating Arg-Gly-Asp-dependent cell adhesion or other phenotypic properties in human neuroblastoma cells.
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PMID:Specific overproduction of very late antigen 1 integrin in two human neuroblastoma cell lines selected for resistance to detachment by an Arg-Gly-Asp-containing synthetic peptide. 278 39

Adhesion responses of fibroblasts (Balb/c 3T3 cells) and human neuron-derived (Platt neuroblastoma) cells have been examined with plasma fibronectin (pFN) adsorbed to glass surfaces derivatized with an alkyl chain and six chemical end groups interfacing with the bound pFN to test regulation of pFN function. Using new derivatization protocols, the following surfaces have been tested in order of increasing polarity: [CH3], [C = C], [Br], [CN], [Diol], [COOH], and underivatized glass [( SiOH]). For all substrata, pFN bound equivalently using either a supersaturating amount of pFN or a subsaturating amount in competition with bovine albumin. Attachment of both cell types was also equivalent on all substrata. However, spreading/differentiation responses varied considerably. F-actin reorganization was tested in 3T3 cells with rhodamine-phalloidin staining. While stress fibers formed effectively on pFN-coated [SiOH] and [Br] substrata, only small linear bundles of F-actin and a few thin stress fibers were observed on the [COOH], [Diol], and [CN] substrata; the hydrophobic substrata [( CH3] and [C = C]) gave an intermediate response. When a synthetic peptide containing the Arg-Gly-Asp-Ser sequence required for integrin binding to FNs was included in the medium as an inhibitor, additional differences were noted: Stress fiber formation was completely inhibited on [SiOH] but not on [Br] and stress fiber formation was very sensitive to inhibition on the hydrophobic substrata while the F-actin patterns on the [CN] and [COOH] substrata were unaffected. Evaluation of neurite outgrowth by neuroblastoma cells on these substrata revealed both qualitative and quantitative differences as follows: [Diol] = [COOH] greater than [SiOH] much greater than [CN] = [Br] greater than [CH3] = [C = C]. While there was poor cytoplasmic spreading and virtually no neurites formed on the hydrophobic surfaces when pFN alone was adsorbed, neurite formation could be "rescued" if a mixture of pFN with an excess of bovine albumin was adsorbed, demonstrating complex conformational interactions between substratum-bound pFN and adhesion-inert neighboring molecules. In summary, these studies demonstrate that different chemical end groups on the substratum modulate pFN functions for cell adhesion, principally by affecting the conformation of these molecules rather than the amounts bound. Furthermore, these studies confirm multiple-receptor interactions with the FN molecules in cell type-specific adhesion patterns.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Modulation of fibronectin adhesive functions for fibroblasts and neural cells by chemically derivatized substrata. 280 41

Rat brain neuropeptide Y precursor (prepro-NPY) cDNA clones were isolated and sequenced in order to study regulation of the prepro-NPY gene. Rat prepro-NPY (98 amino acid residues) contains a 36-residue NPY sequence, followed by a proteolysis/amidation site Gly-Lys-Arg, followed by a 30-residue COOH-terminal sequence. The strong evolutionary conservation of rat and human sequences of NPY (100%) and COOH-terminal peptide (93%) suggests that both peptides have important biological functions. In the rat central nervous system, prepro-NPY mRNA (800 bases) is most abundant in the striatum and cortex and moderately abundant in the hippocampus, hypothalamus, and spinal cord. The rat adrenal, spleen, heart, and lung have significant levels of prepro-NPY mRNA. Regulation of the prepro-NPY mRNA abundance was studied in several rodent neural cell lines. PC12 rat pheochromocytoma and N18TG-2 mouse neuroblastoma cells possess low basal levels of prepro-NPY mRNA, while NG108-15 hybrid cells possess high levels. Treatment of PC12 cells with a glucocorticoid such as dexamethasone or elevation of cAMP by forskolin increased the prepro-NPY mRNA level 2-3-fold or 3-10-fold, respectively. In N18TG-2 cells dexamethasone and forskolin synergistically increased prepro-NPY mRNA 7-fold. Treatment of PC12 cells with the protein kinase C activator phorbol 12-myristate 13-acetate alone elevated prepro-NPY mRNA marginally, but the phorbol ester plus forskolin elicited 20-70-fold increases, which were further enhanced to over 200-fold by dexamethasone and the calcium ionophore A23187. These results indicate that NPY gene expression can be positively regulated by synergistic actions of glucocorticoids, cAMP elevation, and protein kinase C activation.
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PMID:Rat neuropeptide Y precursor gene expression. mRNA structure, tissue distribution, and regulation by glucocorticoids, cyclic AMP, and phorbol ester. 283 71


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