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)

The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.
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PMID:Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay. 127 91

Gene expression of nerve growth factor receptor (NGFR), epidermal growth factor receptor(EGFR), chromogranin A (CGA) and neuropeptide Y (NPY) in 4 neuroblastoma cell Lines without N-myc amplification was studied by using Northern blot technique. N type cells expressed more NGFR mRNA than S type cell's and have only little or no EGFR expression. S type cells had stronger expression of EGFR mRNA than that of N type cells accompanying with only less or even no NGFR expression. The results indicated that difference of gene expression of these growth factor receptors might be due to the various directions of tumor cell differentiation. Cells differentiating toward neurons gave more NGFR expression and cells prepared to be differentiating toward other direction might give more EGFR gene expression. Various gene expression of CGA and NPY in neuroblastoma cell lines might be due to the presence of different stages of tumor cell differentiation and NGF only induced differentiation of those neuroblastoma cells ready to be differentiating to neurons afterwards.
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PMID:[Gene expression of NGFR, EGFR, CGA, NPY in 4 neuroblastoma cell lines]. 132 22

1. We investigated the usefulness of neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma using a simple and highly sensitive r.i.a. for human neuropeptide Y. 2. Plasma immunoreactive neuropeptide Y concentrations were measured without extraction in plasma samples (100 microliters) from patients with various diseases. 3. The plasma immunoreactive neuropeptide Y concentration in patients with phaeochromocytoma (172.3 +/- 132.4 pmol/l, mean +/- SD, n = 23) was significantly higher than that in healthy adult subjects (40.1 +/- 10.1 pmol/l, n = 40, P < 0.0001). The plasma immunoreactive neuropeptide Y concentrations in patients with ganglioneuroblastoma (590.7 +/- 563.6 pmol/l, n = 6) and patients with neuroblastoma (566.9 +/- 524.4 pmol/l, n = 15) were significantly higher than those in control children (1-9 years old, 82.2 +/- 39.9 pmol/l, n = 72, P < 0.0001). 4. The plasma immunoreactive neuropeptide Y concentration in patients with essential hypertension (34.0 +/- 3.7 pmol/l, n = 18) was within the normal range, but in patients with chronic renal failure undergoing maintenance haemodialysis (192.1 +/- 68.0 pmol/l, n = 25) and in non-dialysed patients with chronic renal failure (85.1 +/- 23.1 pmol/l, n = 7) it was significantly higher than that in healthy adult subjects (P < 0.0001). 5. Eighty-seven per cent of the patients with phaeochromocytoma, 67% of the patients with ganglioneuroblastoma and 80% of the patients with neuroblastoma showed plasma immunoreactive neuropeptide Y concentrations higher than the upper limits in the control subjects [62 pmol/l (adult) and 160 pmol/l (children)].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma. 132 37

The signal transduction systems of the neuropeptide Y (NPY) Y1 receptor were studied in SK-N-MC human neuroblastoma cells. NPY induced an increase in intracellular calcium ion concentration ([Ca2+]i) and inhibition of forskolin-stimulated cyclic AMP accumulation, which were mediated through Y1 receptors. One-min preincubation of cells with phorbol 12-myristate 13-acetate (PMA) inhibited both signal transductions dose-dependently, but its effect on [Ca2+]i was about 100-fold more potent than that on cyclic AMP. PMA had no effect on [125I]BH-NPY binding in SK-N-MC cells and hardly inhibited the endothelin-1-induced increase in [Ca2+]i. Pertussis toxin also inhibited the NPY-induced [Ca2+]i increase 30-fold more effectively than the NPY-mediated inhibition of cyclic AMP accumulation. These results indicate that Y1 receptors in SK-N-MC cells couple to two signal transduction systems that have different sensitivities to phorbol ester and pertussis toxin treatments.
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PMID:Two different signal transductions of neuropeptide Y1 receptor in SK-N-MC cells. 132 39

We have demonstrated that the mouse neuroblastoma N18Tg2 cell line and several clones of hybrid ND cells (ND7, ND9 and ND21), derived from the fusion of neonatal rat sensory neurons with that neuroblastoma, show immunostaining to protein gene product 9.5, neuropeptide Y, C-flanking peptide of neuropeptide Y, tyrosine hydroxylase and chromogranins. Synaptophysin could only be detected in ND cells. Immunoreactivities to substance P, calcitonin gene-related peptide, galanin and somatostatin could not be detected in any of these cell lines. After three days of incubation in a differentiation medium, cell processes of various lengths were observed both in neuroblastoma and ND cell cultures. In ND7 cells there was also a redistribution of neuropeptide Y and its C-flanking peptide to the tips of cell processes. The differentiation of cell processes was also accompanied by the appearance of immunostaining to rat chromogranins in their tips. In contrast, synaptophysin expression was found mainly in cell bodies. Neuropeptide Y, its C-flanking peptide and chromogranins have been associated with secretory granules, whereas synaptophysin is a marker for small synaptic-like vesicles. Therefore, our morphological findings further support and expand the view that these markers are primarily associated with different subcellular structures. Moreover, they indicate that the regulated secretory pathway associated with chromogranins is segregated into nerve processes at an early stage of differentiation, when the synaptophysin-associated pathway is not yet mature. ND7 cells thus provide a useful model system for studying changes in the distribution of neuropeptides, cytoskeletal elements and proteins associated with cell secretion during neuronal differentiation.
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PMID:Intracellular redistribution of neuropeptides and secretory proteins during differentiation of neuronal cell lines. 134 12

Treatment of SH-SY5Y human neuroblastoma cells with the protein kinase inhibitor staurosporine, induced both morphological and functional differentiation in these cells. The effects of staurosporine were comparable to those induced by the protein kinase C (PKC) activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA), with respect to induction of neuronal differentiation, i.e. neurite outgrowth, inhibition of DNA synthesis, induction and down-regulation of c-myc protein expression, induction of mRNA for both neuropeptide Y (NPY) and growth associated protein 43 (GAP-43) and stimulation of tyrosine hydroxylase expression. Staurosporine failed to translocate PKC to the membrane fraction or to stimulate phosphorylation of the endogenous PKC substrate M(r) 80,000 (p80). Instead, staurosporine inhibited TPA-induced phosphorylation of p80.
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PMID:Staurosporine induces a neuronal phenotype in SH-SY5Y human neuroblastoma cells that resembles that induced by the phorbol ester 12-O-tetradecanoyl phorbol-13 acetate (TPA). 134 95

Truncated, branched, and/or cyclic neuropeptide Y (NPY) analogues were tested for their ability to bind to the neuroblastoma cells, SK-N-MC (Y1 receptor) and SK-N-BE(2) (Y2 receptor). The design of such analogues was inspired by models of NPY based on the crystal structure of avian pancreatic polypeptide. The minimum length of the backbone was investigated using the following truncated analogues [binding affinity (nM) for Y1 and Y2 receptor subtypes respectively are given in parentheses]: des-AA10-17[D-Ala9]NPY (100, 0.9), des-AA7-23[D-Ala6]NPY (> 1000, 1.2), des-AA4-26[D-Ala3]NPY (> 1000, 120), cyclo(7,20)-des-AA10-17[Glu7,D- Ala9,D-Dpr20]NPY (100, nd), cyclo(2,27)-des-AA7-23[Glu2,D-Ala6,D-Dpr27]NPY (> 1000, 3.6), cyclo(2,30)- des-AA7-23[Glu2,D-Ala6,-D-Dpr30]NPY (> 1000, nd), cyclo(1,30)-des-AA4-26[Glu1,D-Ala3,D-Dpr30]NPY (> 1000, > 1000). A new family of branched NPY analogues corresponding to the partial deletion of the polyproline helix with conservation of the N-terminus was also examined: des-AA7-23[(Ac-NPY14-22)-epsilon-D-Lys6]NPY (> 1000, 2.1), des-AA7-23[(Ac-NPY7-22)-epsilon-D-Lys6]NPY (> 1000, 5.1), des-AA7-23-[(Ac-LEALEG-NPY14-22)-epsilon-D-Lys6]NPY (> 1000, 4.8). Finally, the role played by the flexible tail (residues 32-36) was studied with the following cyclic analogues: cyclo(30,34)-[Lys30,Glu34]NPY18-36 (> 1000, 360), cyclo(30,34)-[Orn30,Gly34]NPY18-36 (> 1000, 950), cyclo(30,34)-[Dpr30,Glu34]NPY18-36 (> 1000, 590), cyclo(33,36)-[Lys33,Glu36]NPY (> 1000, > 1000), cyclo(33,36)-[Lys33,Glu36]NPY18-36 (> 1000, > 1000). These results suggest that the Y1 receptor is highly discriminatory since deletion of residues 10-17, shown to have little effect on Y2 binding affinity, reduces Y1 affinity 50-fold. Bridging sites and constructs have been identified that may serve as useful leads in the design of more potent and selective analogues. We have identified two positions (9 and 6) where the introduction of a D amino acid is not detrimental to binding affinity. Whether this modification leads to the stabilization of a yet unidentified turn compatible with high Y2 receptor affinity will have to be determined by spectroscopic methods. Finally, stabilizing a putative alpha-helical conformation of the C-terminal heptapeptide of NPY18-36 has a deleterious effect on the Y1 and Y2 receptors.
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PMID:Truncated, branched, and/or cyclic analogues of neuropeptide Y: importance of the pancreatic peptide fold in the design of specific Y2 receptor ligands. 143 76

We have studied [125I]neuropeptide Y-binding sites and neuropeptide Y-mediated second messenger responses in human SK-N-MC neuroblastoma cells with special reference to the role of G-proteins. Neuropeptide Y stimulated two second messenger responses in SK-N-MC cells, inhibition of cAMP accumulation and mobilization of Ca2+ from intracellular stores. Both effects were completely abolished by pretreatment with pertussis toxin. Binding of [125I]neuropeptide Y to intact cells or SK-N-MC cell membranes was rapid, reversible, characterized by high affinity and low capacity, and had pharmacological characteristics of a homogeneous population of Y1-like neuropeptide Y receptors. In permeabilized cells, [125I] neuropeptide Y binding was inhibited by GTP gamma S in a concentration-dependent manner. Saturation experiments in the absence and presence of GTP gamma S demonstrated a reduction in the number of high-affinity [125I]neuropeptide Y-binding sites without a decrease in affinity of the remaining sites. Pretreatment of intact cells with pertussis toxin completely abolished the inhibition of [125I]neuropeptide Y binding by GTP gamma S. Moreover, pertussis toxin treatment reduced the number of high-affinity [125I]neuropeptide Y binding sites. We conclude that the agonist ligand [125I]neuropeptide Y identifies functional neuropeptide Y receptors in SK-N-MC cells; however, the number of specific [125I]neuropeptide Y-binding sites may not necessarily reflect the number of neuropeptide Y receptors, because the former is affected by the functional state of cellular G-proteins.
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PMID:G-protein coupling and signalling of Y1-like neuropeptide Y receptors in SK-N-MC cells. 166 84

D-myo-Inositol-1,2,6-trisphosphate (PP56) is a novel experimental drug which is structurally related to the intracellular second messenger IP3. Among other pharmacological effects, PP56 has been shown to antagonize neuropeptide Y (NPY) induced vasoconstriction with a high degree of specificity. We examined the effects of i.c.v. PP56 on locomotor activity and food intake in rats, and on the hypoactivity and hyperphagia induced by NPY. In the open field, PP56 given alone increased locomotor activity by up to 85%. It did not prevent NPY induced hypoactivity to any extent. PP56 given alone did not affect food intake except for a small increase after the highest dose tested (200 nmol). When NPY was given after pretreatment with PP56, NPY induced hyperphagia was significantly reduced. A similar effect, however, was seen with regard to the hyperphagia produced by another orexigenic peptide, galanin. PP56 did not affect the binding of 125I-NPY to brain membranes in vitro, or to cells of two different neuroblastoma cell lines which selectively express NPY Y1 or Y2 receptors. In summary, PP56 acted as a locomotor stimulant per se. Only one of the two tested central effects of NPY could be antagonized by PP56, and then only partially and in a non-specific manner. The central effects of PP56 do not seem to be produced at the level of NPY receptors.
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PMID:Effects of intracerebroventricular D-myo-inositol-1,2,6-trisphosphate (PP56), a proposed neuropeptide Y (NPY) antagonist, on locomotor activity, food intake, central effects of NPY and NPY-receptor binding. 166 39

Two types of binding sites have previously been described for 36-amino acid neuropeptide Y (NPY), called Y1 and Y2 receptors. Y2 receptors can bind long C-terminal fragments of NPY-e.g., NPY-(13-36)-peptide. In contrast, Y1 receptors have until now only been characterized as NPY receptors that do not bind such fragments. In the present study an NPY analog is presented, [Leu31, Pro34]NPY, which in a series of human neuroblastoma cell lines and on rat PC-12 cells can displace radiolabeled NPY only from cells that express Y1 receptors and not from those expressing Y2 receptors. The radiolabeled analog, [125I-Tyr36] monoiodo-[Leu31, Pro34]NPY, also binds specifically only to cells with Y1 receptors. The binding of this analog to Y1 receptors on human neuroblastoma cells is associated with a transient increase in cytoplasmic free calcium concentrations similar to the response observed with NPY. [Leu31, Pro34]NPY is also active in vivo as it is even more potent than NPY in increasing blood pressure in anesthetized rats. It is concluded that [Leu31, Pro34]NPY is a specific Y1 receptor agonist and that the analog or variants of it can be useful in delineating the physiological importance of Y1 receptors.
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PMID:[Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist. 215 86


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