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 phenylalanine analogues p-chlorophenylalanine and alpha-methylphenylalanine were used to inhibit phenylalanine hydroxylase in animal models for phenylketonuria. The present report examines the affects of these analogues on the metabolism of neuroblastoma cells. p-Chlorophenylalanine inhibited growth and was toxic to neuroblastoma cells. Although in vivo this analogue increased cell monoribosomes by 42%, it did not significantly affect poly(U)-directed protein synthesis in vitro. P-Chlorophenylalanine did not compete with phenylalanine or tyrosine for aminoacylation of tRNA and was therefore not substituted for those amino acids in nascent polypeptides. The initial cellular uptake of various large neutral amino acids was inhibited by this analogue but did not affect the flux of amino acids already in the cell; this suggested that an alteration of the cell's amino acid pools was not responsible for the cytotoxicity of the analogues. In contrast with p-chlorophenylalanine, alpha-methylphenylalanine did not exert these direct toxic effects because the administration of alpha-methylphenylalanine in vivo did not affect brain polyribosomes and a comparable concentration of this analogue was neither growth inhibitory nor cytotoxic to neuroblastoma cells in culture. The suitability of each analogue as an inhibitor of phenylalanine hydroxylase in animal models for phenylketonuria is discussed.
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PMID:Effects of p-chlorophenylalanine and alpha-methylphenylalanine on amino acid uptake and protein synthesis in mouse neuroblastoma cells. 15 35

A bioactive, fluorescent derivative of enkephalin, Tyr-D-Ala-Gly-Phe-Leu-Lys-rhodamine, was used to determine the distribution of opiate receptors in living neuroblastoma cells. The receptors appeared in clusters on the cell surface, and no internalization was detected. No specific fluorescence or clusters were observed in the presence of [D-Ala2, Leu5]enkephalin or at 4 degrees C, and the clusters were much reduced under ionic conditions (that is, with 100 millimolars sodium) that specifically decrease the binding of opiate agonists.
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PMID:Opiate (Enkephalin) receptors of neuroblastoma cells: occurrence in clusters on the cell surface. 22 58

Peptichemio (PTC) is a mixture of six synthetic peptides of m-L-phenylalanine mustard. It acts with both alkylating and antimetabolic effects, interfering with the synthesis of DNA, RNA, and proteins. PTC was administered iv to 18 previously untreated children with advanced neuroblastoma at a dose of 1-1.5 mg/kg/day for one to three cycles of 5-6 consecutive days each. Eleven of 12 patients (92%) experienced both objective and subjective improvement; complete remission was achieved in two of them. In spite of the high remission rate, the median duration of remission has been short (4 months) and the overall survival (median, 6 months) did not seem to be influenced by the use of PTC. The primary toxic effects were, in order of importance, bone marrow depression, phlebosclerosis, nausea and vomiting, and alopecia. Chronic use of PTC seems limited by two major factors: profound long-lasting thrombocytopenia and severe phlebosclerosis.
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PMID:Peptichemio in advanced neuroblastoma. 65 65

Cloned neuroblastoma cell lines derived from the spontaneous mouse tumor C-1300 were used to study nerve cell differentiation. Our findings included a) morphologic and electrical differentiation was induced by the addition of dimethyl sulfoxide to the culture medium of some of the neuroblastoma clonal lines; b) a contrasting difference existed between the percentage of the phenylalanine-specific, tRNA species deficient in the peroxy Y-nucleoside in the mouse embryo or rat brain (6-10%) and that of mouse neuroblastoma cells (85%); c) the assembly of neuroblastoma microtubules and neurofilaments that are necessary for neurite outgrowth proceeded from preexisting pools of tubulin and actin, but a sustained level of phosphorylated tubulin was not required for this regulation; and d) the in vitro translation of tubulin and actin was accomplished with mRNA from rat brains in a wheat-germ cellfree system.
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PMID:Properties and synthesis of tubulin in neuroblastoma cells. 78 6

Affinity chromatography on anti-Y (Y is a tricyclic imidazopurine to which is attached a complex four-carbon side chain) antibody immobilized to Sepharose was used to determine the proportion of rat liver tRNAPhe species containing the peroxy Y-nucleoside. Unfractionated Unfractionated mammalian tRNA was aminoacylated with labeled phenylalanine. The phenylalanyl-tRNA was then chemically acetylated to yield N-acetylphenylalanyl-tRNA. When this preparation was applied to the antibody column, between 6-10% of the radioactivity was not bound to the column, indicating a deficiency of peroxy Y-nuceloside in a minor isoaccepting tRNAPhe species. In contrast to normal tissues (including embryonic tissue), about 85% of the tRNAPhe from mouse neuroblastoma C-1300 or N-18 tumors lack the peroxy Y-base, a property which is not affected by tumor age. Rat liver labeled N-acetylphenylalanyl-tRNA preparations were resolved on Plaskon chromatography (RPC-5) into two minor peaks closely followed by a mojor component. A high proportion of the two minor tRNAPhe species was unable to bind to anti-Y antibodies. Upon mild acid treatment, the minor and major tRNAPhe species eluted simultaneously from Plaskon columns, at a much reduced salt concentration. These results would indicate that the two minor tRNAPhe species from rat liver as well as the major component contain a tricyclic imidazopurine base that differs from each other in its side chain. About 85% of the N-acetylphenylalanyl-tRNA from neuroblastoma was resolved by Plaskon chromatography as an early eluting peak. The position of this major neuroblastoma tRNAPhe species was not altered by mild acid treatment, and its elution position from the column almost coincides with that of acid-treated normal rat liver tRNAPhe. The latter results would suggest that most of the tRNAPhe chains from neuroblastoma lack the tricyclic imidazopurine of normal rat liver tRNAPhe, but are very close if not identical in primary nucleotide sequence.
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PMID:Abundance of tRNAPhe lacking the peroxy Y-base in mouse neuroblastoma. 99 5

In order to develop systemically-active opioid peptides, the delta-selective, opioid pentapeptide [D-Pen2,D-Pen5]-enkephalin (DPDPE) was modified by esterification and by substitution of 2',6'-dimethyltyrosine for tyrosine to yield 4. Compound 4 was on the order of 8- and 800-fold more active than DPDPE in both delta and mu opioid radioligand binding assays, respectively, in rat neural membrane suspensions. Compound 4 was considerably more potent than DPDPE at inhibiting contractions of electrically-stimulated mouse vas deferens in vitro, and this effect was very sensitive to naltrindole, a delta-selective opioid antagonist. These observations can be taken as indication that 4 exerts its effects through delta opioid receptors. This interpretation is supported by the finding that the EC50 value of 4 derived in the smooth muscle assay is very similar to that derived in NG108-15 neuroblastoma cells, a preparation devoid of mu receptors. Unlike DPDPE, 4 exhibited significant, naloxone-sensitive, antinociceptive activity when administered systemically, as measured by inhibition of phenylbenzquinone-induced stretching in mice (ED50 = 2.1 mg/kg). Compound 4 also displayed significant antinociceptive activity following systemic administration as measured by its action in mice to increase latencies for tail withdrawal from radiant heat (ED50 = 50 mg/kg). Compound 4 did not produce morphine-like discriminative stimulus effects in rats trained to discriminate 3.0 mg/kg morphine from vehicle at doses ranging from 30 to 120 mg/kg. This observation can be interpreted as indication that within this dosage range there is an absence of morphine-like subjective effects. Physical dependence, however, could be induced in mice at higher doses of 4 under a progressively-graded, 4-day dose regimen. Congeners of 4 with amide bond surrogates for the Gly-Phe amide bond (oxymethylene, trans-double bond, and bismethylene isosteres) in the cyclic core of DPDPE were prepared in an attempt to increase the antinociceptive activity of 4. While some of the congeners were active in the in vitro assays, they did not display significant antinociceptive activity following systemic administration. The preparation of all the compounds was accomplished by solution-phase methods. The mechanisms which might underlie the biological and systemic activity of 4 are discussed.
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PMID:Analogs of the delta opioid receptor selective cyclic peptide [2-D-penicillamine,5-D-penicillamine]-enkephalin: 2',6'-dimethyltyrosine and Gly3-Phe4 amide bond isostere substitutions. 132 77

ANP-R1 receptors for atrial natriuretic peptide (ANP) showed the following rank order of affinity in intact human neuroblastoma cells NB-OK-1: human ANP-(99-126) approximately human ANP-(102-126) approximately rat ANP-(99-126) (K1 17-32 pM) > human ANP-(103-126) > porcine brain natriuretic peptide (BNP). Analogues truncated at the C-terminal extremity or devoid of a disulphide bridge, such as rat ANP-(103-123), rat C-ANP-(102-121), rat ANP-(111-126), rat ANP-(99-109) and rat [desCys105,Cys121]ANP-(104-126) and chicken C-type natriuretic peptide, were not recognized. The occupancy of these high affinity ANP-R1 receptors led to marked cyclic GMP accumulation in the presence of 3-isobutyl 1-methylxanthine. An ectoenzymic activity, partly shed in the incubation medium, provoked the stepwise release of Phe-Arg-[125I]Tyr, Arg-[125I]Tyr and [125I]Tyr from rat [125I]ANP-(99-126), at an optimal pH of 7.0. Its inhibition by 1,10-phenanthroline, EDTA and bacitracin but not by thiorphan suggests the contribution of at least one neutral metalloendopeptidase, distinct from EC 3.4.24.11, for which ANP showed high affinity.
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PMID:Atrial natriuretic peptide binds to ANP-R1 receptors in neuroblastoma cells or is degraded extracellularly at the Ser-Phe bond. 133 13

To better understand opioid binding parameters found in situ, binding studies were conducted to mu-opioid receptors on intact SH-SY5Y neuroblastoma cells and compared with binding to SH-SY5Y membrane and guinea pig brain membrane preparations. The mu-selective peptide antagonist [3H]D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) was used for the binding studies. The fact that CTOP is an antagonist and hydrophilic is important for binding to be achieved using intact cells. In intact cells, using a physiological buffer, there appears to be only a low affinity "agonist" conformation of the receptor. This is in contrast to binding in either brain or SH-SY5Y membranes in Tris buffer, in which high-affinity agonist binding was prevalent. As expected from the binding profiles, pertussis toxin treatment of cells has no effect on binding to intact cells, but significantly decreases affinity of agonists to cell membranes. In intact cells, binding appears to be to a single site and a single state of the mu receptor. Although in membrane preparations inhibition curves are shallow, with slope factors less than 1.0 for many agonists, on intact cells agonist inhibition curves are very steep, with slope factors slightly greater than 1.0.
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PMID:Comparison of mu opioid receptor binding on intact neuroblastoma cells with guinea pig brain and neuroblastoma cell membranes. 134 68

The synthetic undecameric peptide, pGlu-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe, known as the hydra head activator peptide, present in high concentrations in mammalian hypothalamus and intestine, was tested for neurotrophic activity in a survival assay using cultured chick embryonic sympathetic and dorsal root ganglion cells, and for morphological differentiation activity on neuroblastoma cells. Hydra head activator peptide supported neuron survival. The optimal active concentration, 1 pM, was very similar to the concentration that causes bud and head formation in hydra. Maximal neuron survival obtained with hydra head activator peptide was close to that obtained with nerve growth factor: both substances enhanced survival up to 3 times that of control cultures. Bradykinin, which has some amino acid sequence homology with hydra head activator, was inactive as a neurotrophic factor. Hydra head activator induced rapid morphological differentiation of the mouse neuroblastoma cell line Neuro-2A. Neuro-2A responded to the peptide by process extension, 4 h after its addition to the culture medium. Neurotrophic factors isolated to date have been characterized by their ability to maintain cell viability and enhance neurite outgrowth. Hydra head activator peptide met these two criteria when tested in 3 different neuron culture systems. Our results suggest that the head activator peptide may act as a neurotrophic factor for neurons in other species, including mammals.
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PMID:Hydra head activator peptide has trophic activity for eukaryotic neurons. 152 28

A novel metallo-endopeptidase from human neuroblastoma NB-OK-1 cells was partially purified and characterized. This enzyme activity was detected in the culture medium and could be detached from intact cells by gentle washing, suggesting a peripheral localization of the enzyme. This endopeptidase inactivated Atrial Natriuretic Peptide (ANP) by a unique and selective cleavage of the Ser123-Phe124 bond. It also produced hydrolysis at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bonds of other peptide hormones such as bradykinin, somatostatin 14, litorin, substance P, neuromedin C and angiotensin II. The substrate selectivity and inhibition profile of the enzyme showed obvious similarities with the peptide hormone inactivating endopeptidase (PHIE) recently purified from Xenopus laevis skin secretions and indicated a thermolysin-like activity distinct from neutral endopeptidase (EC 3.4.24.11) and from angiotensin converting enzyme (EC 3.4.15.1).
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PMID:A new metallo- endopeptidase from human neuroblastoma NB-OK-1 cells which inactivates atrial natriuretic peptide by selective cleavage at the Ser123-Phe124 bond. 153 Oct 11


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