UMLS:C0027819 - FACTA Search

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Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iodinated human beta-endorphin was affinity-cross-linked to opioid receptors present in membrane preparations from bovine frontal cortex, bovine striatum, guinea pig whole brain, and rat thalamus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography revealed covalently labeled peptides of 65, 53, 41, and 38 kilodaltons (kDa). The 65- and 38-kDa peptides were present in all four tissues. The 41-kDa peptide was seen only in bovine caudate and guinea pig whole brain while the 53-kDa peptide was absent in rat thalamus. All four labeled peptides were constituents of opioid receptors since their labeling was fully suppressed by the presence of excess opiates, such as bremazocine, during binding. The distribution and levels of the labeled species in the brain tissues examined and, in earlier work, in the neuroblastoma X glioma NG 108-15 cell line suggested that the 65-kDa peptide is a binding component of mu receptors while the 53-kDa peptide is a binding subunit of delta receptors. This result was strongly supported by the finding that the labeling of the 65-kDa peptide is selectively reduced by the presence of the highly mu-selective ligand Tyr-D-Ala-Gly-(N-Me)Phe-Gly-ol (DAMGE) during binding, while while the labeling of the 53-kDa peptide is selectively reduced or eliminated by the highly mu-selective ligand [D-Pen2, D-Pen5]enkephalin (DPDPE). The labeling of the 41- and 38-kDa bands was reduced by either DAMGE or DPDPE. The relationship of these lower molecular weight opioid-binding peptides to mu and delta receptors is not understood. Several possible explanations are presented.
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PMID:Identification of distinct binding site subunits of mu and delta opioid receptors. 300 57

Luteinizing hormone-releasing hormone was degraded by cells of the N-18 line of mouse neuroblastoma and their membrane. Cleavage products were separated by HPLC and identified by amino acid analysis. Fragments (1-3), (4-5), and (6-10) were major cleavage products. All the products increased in level as a function of time except for fragment (1-5), which increased in amount only during a short incubation time and then decreased. The accumulation of fragment (1-5) was increased in the presence of captopril or EDTA, whereas that of fragments (1-3) and (4-5) decreased inversely. On the other hand, the generation of either fragment (1-3) or (4-5) was stimulated by the presence of Cl-. The results suggest that the conversion of fragment (1-5) into fragments (1-3) and (4-5) is catalyzed by angiotensin-converting enzyme. p-Chloromercuribenzoate inhibited the formation of fragment (1-5), a result suggesting the involvement of a thiol protease in this formation. Thus, the degradation of luteinizing hormone-releasing hormone by neuroblastoma cells and their membrane seems to take place mainly through the cleavage of the Tyr5-Gly6 bond by a thiol protease, followed by the release of the dipeptide Ser-Tyr from the liberated fragment (1-5) by angiotensin-converting enzyme. It is further suggested that the thiol protease and angiotensin-converting enzyme are also responsible for the initial minor cleavages of the Gly6-Leu7 bond and the Trp3-Ser4 bond, respectively.
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PMID:Degradation of luteinizing hormone-releasing hormone by neuroblastoma cells and their membrane: evidence for the involvement of a thiol protease and angiotensin-converting enzyme. 302 68

[3H]Az-DTLET (Tyr-D-Thr-Gly-Phe(pN3)-Leu-Thr), a photoaffinity probe for delta opioid receptors binds to a single class of sites in rat brain membranes with a high affinity (KD = 1.66 nM). The selectivity index of Az-DTLET (KI delta/KI mu = 0.036) is better than that of its precursor DTLET (0.053). Rat brain or neuroblastoma glioma cells membranes were incubated with 10 nM [3H]Az-DTLET, washed and irradiated with U.V. After irradiation a fraction (20-30%) of specific binding was found to remain indissociable after 10 min at 60 degrees C and was considered as irreversible. This fraction increased as a function of the irradiation time. The radioactivity irreversibly bound to rat brain membranes, solubilized by sodium cholate, was associated with high molecular weight species (200,000 daltons). In denaturing conditions (SDS 2%), the [3H]Az-DTLET specific binding was associated with molecular components of 45-50 K and 90-100 K daltons. In contrast, when opioid receptors were prelabelled by [3H]Az-DTLET, solubilized by Na-cholate and irradiated, the radioactivity was only recovered with subunits of 45-50 K daltons. The autoradiographic localization of the irreversibly bound [3H]Az-DTLET in rat brain was identical to that of reversibly bound [3H]DTLET or [3H]Az-DTLET. These results suggest that [3H]Az-DTLET represents an adequate specific probe for studies on the structure, function and anatomical distribution at light and even electron microscopic level of delta-opioid receptors.
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PMID:Irreversible labelling of delta-opioid receptors in rat brain and neuroblastoma cells by [3H]azido-DTLET: characterization of subunits and autoradiographic visualization of the covalent binding. 303 96

A membrane-bound enkephalin (ENK) -hydrolyzing amino-peptidase (AP) was partially purified from neuroblastoma (clone N1E-115) cell membranes; enzyme activity was assayed by determination of the leu-enkephalin (LENK) degradation product, tyrosine (Tyr), with HPLC. The enzyme was extracted with Triton X-100, resolved by anion-exchange chromatography and further purified by gel filtration. The overall purification was about 100-fold with a yield of 43%. The apparent Mr value of the AP by gel filtration in the presence of 0.3% Triton X-100 was approx. 400 kDa. In the absence of detergent the apparent Mr value was about 305 kDa. In the elution buffers, where Triton X-100 was omitted, the peptidase activity was lost. The enzyme had a Km of 0.13 mM and a Vmax of 450 nmoles per mg protein per min at 25 degrees C for LENK and exhibited little sensitivity to bestatin (IC50: 200 microM) and puromycin (IC50: 500 microM), but it was strongly inhibited by amastatin (IC50: 8 microM). The enzyme is an amphiphilic membrane protein; the native primary structure is preserved only in the 'detergent form'. It seems to be AP N (EC 3.4.11.2) with an optimum of pH 7.2 to 7.4. We assume that this AP plays the important role in inactivating ENKs on the neuronal level. The ENK-degrading AP, partially purified from primary rat brain astrocyte cell membranes, exhibited a smaller apparent Mr value (130 kDa) and a higher sensitivity to amastatin (IC50: 0.4 microM), bestatin (IC50: 90 nM) and puromycin (IC50: 5 microM) than did the N1E-115 enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the enkephalin-degrading aminopeptidase of neuroblastoma (N1E-115) cell membranes. 312 43

We have compared in different human neuroblastoma cell lines and human glioblastoma cells the expression level, structure, and tyrosine-specific protein kinase activity of pp60c-src. Our results show that not all human neuroblastoma cell lines express pp60c-src molecules with amino-terminal structural alterations. In neuroblastoma cells which possess pp60c-src with altered gel migration, the diminished polyacrylamide gel mobility of pp60c-src was found not to be dependent upon amino-terminal phosphorylations since extensive treatment of these molecules with phosphatase did not significantly change their gel migration properties. Similar differences in gel migration were observed when RNA from the various neuroblastoma and glioblastoma cells was translated in vitro using either rabbit reticulocyte or wheat germ lysates. White the level of c-src mRNA in the different cells analyzed was found to be similar, the abundance of pp60c-src in these same cells was found to vary by as much as 12-fold. This suggests that the abundance of pp60c-src in human neuroendocrine tumors is regulated through post-transcriptional and/or post-translational events which may be related to the stage of neuronal differentiation of the cells. Based upon determination of pp60c-src abundance by immunoblot analysis, we demonstrate that pp60c-src molecules derived from human neuroblastoma and glioblastoma cells have very similar in vitro protein kinase activities.
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PMID:Analysis of the c-src gene product structure, abundance, and protein kinase activity in human neuroblastoma and glioblastoma cells. 314 45

It is clear that there are at least two classes of cancer-related genes. The more characterized of these are the oncogenes, whose activation appears to play a major role in human neoplasia. There are now two families of oncogenes, the myc and ras families, whose cooperation seems capable of transforming normal cells in culture to tumorigenic cells. As such, they appear to form complementation groups with immortalizing and transforming properties, respectively. Moreover, the oncogenes can be subclassified as tyrosine kinases or kinase related, GTP binding proteins, growth factors or growth factor receptors or nuclear proteins. More than 20 viral oncogenes have been identified, for which more than 30 proto-oncogenes or pseudogenes exist in the human genome. Many of these have been cloned, characterized to some extent, and mapped to particular chromosomes or regions of chromosomes. Further, more than 20 additional putative oncogenes or transforming genes have been identified by tumor DNA transfection studies or at sites of integration or translocation for which no viral transforming gene cognates exist. Oncogenes can be activated by increased or unregulated expression, increased copy number (duplication, amplification), or somatic mutation resulting in a protein with increased oncogenic potential. Examples of all of these mechanisms can be found in several specific human cancers or leukemias. The cytogenetic correlate of enhanced expression is a translocation between two chromosomes at specific breakpoints with no net loss of genetic material (e.g., increased c-myc expression resulting from the 8;14 translocation in Burkitt's lymphoma). The phenomenon of increased gene copy number can sometimes be visualized as trisomy or tetrasomy for a particular chromosome but more dramatically as the development of extrachromosomal DMs or as chromosomally integrated HSRs (e.g., the N-myc gene amplification seen in neuroblastoma). Finally, certain somatic mutations can be associated with translocations (e.g., the bcr/abl fusion product created as a result of the 9;22 translocation in chronic myelogenous leukemia), but they are more commonly submicroscopic (as characterized by point mutations in the ras gene family). Evidence is accumulating for a second class of cancer-related genes whose absence or inactivation is associated with tumorigenesis. These genes are associated at the cytogenetic level with chromosomal deletions, in which the breakpoints may be variable, but specific, common regions are consistently deleted.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The involvement of oncogenes and suppressor genes in human neoplasia. 331 93

A kinetic analysis of the tyrosine-specific protein kinase of pp60c-src from the C1300 mouse neuroblastoma cell line Neuro-2A and pp60c-src expressed in fibroblasts was carried out to determine the nature of the increased specific activity of the neuroblastoma enzyme. In immune-complex kinase assays with ATP-Mn2+ and the tyrosine-containing peptide angiotensin I as phosphoacceptor substrate, pp60c-src from the neuroblastoma cell line was characterized by a maximum velocity (Vmax.) that was 7-15-fold greater than the Vmax. of pp60c-src from fibroblasts. The neuroblastoma enzyme exhibited Km values for ATP (16 +/- 3 microM) and angiotensin I (6.8 +/- 2.6 mM) that were similar to Km values for ATP (25 +/- 3 microM) and angiotensin I (6.5 +/- 1.7 mM) of pp60c-src from fibroblasts. pp60v-src expressed in Rous-sarcoma-virus-transformed cells exhibited an ATP Km value (25 +/- 4 microM) and an angiotensin I Km value (6.6 +/- 0.5 mM) that approximated the values determined for pp60c-src in neuroblastoma cells and fibroblasts. These results indicate that the pp60c-src kinase from neuroblastoma cells has a higher turnover number than pp60c-src kinase from fibroblasts, and that the neural form of the enzyme would be expected to exhibit increased catalytic activity at the saturating concentrations of ATP that are found intracellularly.
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PMID:Vmax. activation of pp60c-src tyrosine kinase from neuroblastoma neuro-2A. 332 40

Typical insulin receptors are present on neuroblastoma cell lines. High affinity binding for insulin was present in membrane preparations from NG108 (a hybrid mouse neuroblastoma-rat glioma) as well as in membranes from SK-N-MC and SK-N-SH, two human neuroblastoma cell lines. Specific [125I]insulin binding was 24.4% for NG108, 16.9% for SK-N-MC and 5.2% for SK-N-SH at membrane protein concentrations of 0.4 mg/ml. IC50 for [125I]insulin binding was 3.4 nM in NG108 membrane preparations and 0.9 nM for SK-N-SH and 1.8 nM in SK-N-MC membranes. Apparent mol. wt. for the alpha subunits (identified by specific immunoprecipitation using the anti-insulin receptor antiserum B10) on SDS PAGE was 134 kDa for NG108; 124 kDa for SK-N-MC and 120 kDa for SK-N-SH. Neuraminidase digestion increased the mobility of the alpha subunit from both NG108 and SK-N-MC receptors to 120 kDa, whereas that from SK-N-SH were unaffected. Endoglycosidase H and endoglycosidase F digestions increased the mobility of the alpha subunits of all 3 cell lines to varying degrees, suggesting the presence of N-linked glycosylation. Insulin induced autophosphorylation of the insulin receptor beta subunit in WGA-purified membranes from all 3 cell lines. In addition, phosphorylation of a protein with an apparent mol. wt. 105 kDa was stimulated by insulin in WGA purified membranes from NG108. Tyrosine-specific kinase activity was present in the membranes from each cell line and was stimulated by insulin in a dose-dependent manner from 10(-9) to 10(-6) M. Proinsulin was about 100 times less potent in stimulating phosphorylation of the artificial substrate poly (Glu, Tyr)4:1 when compared to insulin in accordance with its lower binding affinity to the insulin receptor. Hexose transport was stimulated by insulin in all 3 cell lines. These results indicate that neuroblastoma cells contain specific insulin receptors and that they may be useful as models for studying the role of insulin in nervous tissue.
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PMID:Characterization of the altered oligosaccharide composition of the insulin receptor on neural-derived cells. 335 62

Five opioid peptides (immunoreactivity) derived from their respective opioid precursors were measured in neuroblastoma-glioma hybrid cells (NG 108CC15; pmol/g protein): heptapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Phe), 13.0 +/- 2.6; alpha-neoendorphin, 6.6 +/- 0.8; dynorphin A, 4.4 +/- 1.5; dynorphin A 1-8, 1.3 +/- 0.29; beta-endorphin, 0.3 +/- 0.13. These peptides originate from preproenkephalin A (heptapeptide), prodynorphin (alpha-neonedorphin, dynorphin A, dynorphin A 1-8) and proopiomelanocortin (beta-endorphin). The data suggest the expression of all three known opioid precursors in a single hybrid cell line, permitting a simultaneous investigation of the processing of different opioid peptides under identical experimental conditions.
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PMID:Evidence for the expression of peptides derived from three opioid precursors in NG 108CC15 hybrid cells. 356 21

The mechanisms by which neurotensin (NT) was inactivated by differentiated neuroblastoma and HT29 cells were characterized. In both cell lines, the sites of primary cleavages of NT were Pro7-Arg8, Arg8-Arg9 and Pro10-Tyr11 bonds. The cleavage at the Pro7-Arg8 bond was totally inhibited by N-benzyloxycarbonyl-Prolyl-Prolinal and therefore resulted from the action of proline endopeptidase. This peptidase also contributed in a major way to the cleavage at the Pro10-Tyr11 bond. However the latter breakdown was partly due to an NT-degrading neutral metallopeptidase. Finally, we demonstrated the involvement of a recently purified rat brain soluble metalloendopeptidase at the Arg8-Arg9 site by the use of its specific inhibitor N-[1(R,S)-carboxy-2-Phenylethyl]-alanylalanylphenylalanine-p-amino benzoate. The secondary processing of NT degradation products revealed differences between HT29 and N1E115 cells. Angiotensin converting enzyme was shown to degrade NT1-10 and NT1-7 in N1E115 cells but was not detected in HT29 cells. A post-proline dipeptidyl aminopeptidase activity converted NT9-13 into NT11-13 in HT29 cells but not in N1E115 cells. Finally bestatin-sensitive aminopeptidases rapidly broke down NT11-13 to Tyr in both cell lines. Models for the inactivation of NT in HT29 and N1E115 cells are proposed and compared to that previously described for purified rat brain synaptic membranes.
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PMID:Catabolism of neurotensin by neural (neuroblastoma clone N1E115) and extraneural (HT29) cell lines. 356 17

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