Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunocytochemical, immunoblotting and in situ hybridization studies were used to map the distribution of SNAP-25 protein and mRNA in the rodent nervous system. These experiments demonstrated that subsets of neurons expressed SNAP-25, and that several patterns of expression emerged: SNAP-25 expression in caudate nucleus was initially concentrated in axons, which subsequently was localized in presynaptic regions of these axons. Other regions, typified by neocortex, showed developmental increases and persistent adult neuronal immunoreactivity for SNAP-25. Finally, olfactory bulb contained neurons which initially expressed SNAP-25, but lost expression during maturation. Additional studies in cultured human and rat cell lines derived from neural crest suggested that SNAP-25 is expressed in such lines, but not in glial or fibroblast lines. Differentiation of rat PC-12 cells with nerve growth factor failed to alter steady-state levels of SNAP-25 protein; similar responses were seen in human SMS-KCNR neuroblastoma cells differentiated using retinoic acid. The presence of SNAP-25 in presynaptic regions of numerous neuronal subsets and in neural crest cell lines suggests that this protein subserves an important function in neuronal tissues.
 ...
PMID:Distribution and expression of SNAP-25 immunoreactivity in rat brain, rat PC-12 cells and human SMS-KCNR neuroblastoma cells. 157 61

Western blot analysis showed that the human neuroblastoma SH-SY5Y expresses the proteins synaptotagmin l, synaptobrevin, synapsin-l, rab3a, syntaxin, SNAP-25, NSF, alpha-SNAP, and munc-18, which have been implicated in the movement, docking, and fusion of vesicles during exocytosis from other neuroendocrine cells. The subcellular localization of secretogranins I and II, synaptotagmin l, neuropeptide Y, rab3a, synaptobrevin, synaptophysin, and syntaxin was investigated by immunofluorescence microscopy and revealed punctate staining patterns characteristic of secretory vesicles. The comigration of noradrenaline, secretogranin II, and dopamine-beta-hydroxylase on sucrose-D2O gradient fractions indicates the presence of a population of noradrenaline-containing large dense-cored vesicles (LDCVs). In addition, a lighter vesicle population is also present that does not appear to be noradrenergic and contains a 48-kDa synaptophysin antigen absent from the large dense-cored vesicles. Immunocytochemical experiments show that not all of the vesicles that express synaptotagmin l contain secretogranin II. Thus, our studies suggest that two types of vesicle are present in SH-SY5Y cells, one of which, the LDCVs, contains noradrenaline. These findings confirm our previous studies suggesting that depolarization-evoked release of noradrenaline from SH-SY5Y occurs by LDCV exocytosis. This enhances the value of SH-SY5Y as a cell line in which to study the mechanism by which noradrenaline release is regulated.
 ...
PMID:Occurrence of two types of secretory vesicles in the human neuroblastoma SH-SY5Y. 908 25

alpha-Synuclein is presynaptic nerve terminal protein and its immunoreactivity has been observed in such neurodegenerative structures as senile plaques of Alzheimer's disease or Lewy bodies of Parkinson's disease. The physiological role of alpha-synuclein is still unknown. It is speculated that alpha-synuclein may be expressed in brain tumors, especially in those showing neuronal differentiation. We examined the immunohistochemical localization of alpha-synuclein in 77 human brain tumors. alpha-Synuclein was widely distributed in the brain tumors showing neuronal differentiation. As a result, positive immunostaining for alpha-synuclein was observed in ganglioglioma, medulloblastoma, neuroblastoma, primitive neuroectodermal tumor, pineocytoma/pineoblastoma, and central neurocytoma. Compared with other neuronal markers, the positive ratio of alpha-synuclein was not as high as synaptophysin, microtubule-associated protein 2, neuron-specific enolase and tau, but it was higher than neurofilament and chromogranin A. The expression of synaptophysin was diffusely observed in the cytoplasm, cellular processes and nucleus in tumors showing neuronal differentiation; however, the expression of alpha-synuclein was predominantly observed in the cytoplasm of the tumors as well as in the cellular processes. On the other hand, non-neuronal brain tumors such as astrocytic tumors or meningiomas were totally negative for alpha-synuclein. In conclusion, the appearance of an alpha-synuclein-positive structure was not limited to neurodegenerative diseases, but could also be detected in neoplastic cells showing neuronal differentiation.
 ...
PMID:alpha-Synuclein is expressed in a variety of brain tumors showing neuronal differentiation. 1067 22

Exocytosis is mediated by high-affinity interactions between different SNARE proteins. The existence of several variants of each SNARE protein suggests that the specificity of fusion may be directed by unique combination of SNARE family members. We examined if two alternatively spliced variants of synaptosomal-associated protein of 25 kD, SNAP-25a and SNAP-25b, possessed distinct cellular distribution if coexpressed within the same neuroblastoma cell. Double-labelling immunofluorescence histochemistry in combination with confocal laser microscopy of individual cell clones revealed a different subcellular localisation pattern for the two SNAP-25 variants. Sucrose density gradient centrifugation of cell homogenates followed by Western blotting showed that the SNAP-25 protein variants associated with intracellular organelles of different density. Taken together, this study shows that two alternatively spliced variants of SNAP-25, differing in only nine amino acids, possess distinct properties at the level of intracellular trafficking, suggesting that the cellular localisation of SNAP-25 protein is regulated at the level of mRNA splicing.
 ...
PMID:Differential sorting of SNAP-25a and SNAP-25b proteins in neuroblastoma cells. 1113 40

The role of rat neuronal calcium sensor-1 (NCS-1), a Ca2+-binding protein, in synapse formation and transmitter release was examined in mouse neuroblastoma x rat glioma hybrid NG108-15 cells in culture. Wild-type NG108-15 cells expressed rodent NCS-1. Endogenous NCS-1 was partially co-localized with the synaptic protein SNAP-25 at the plasma membrane in both cell bodies and processes, but not with the Golgi marker [beta]-COP, an individual coat subunit of the coatomer complex present on Golgi-derived vesicles. In NG108-15 cells co-cultured with rat myotubes, partial co-localization of SNAP-25 and NCS-1 was observed at the plasma membrane of neurites and growth cones, some of which had synaptic contacts to muscle cells. Transient co-transfection of the rat NCS-1 cDNA and green fluorescent protein (GFP) resulted in NCS-1 overexpression in about 30 % of the cells as determined by fluorescence microscopy. The rate of functional synapse formation with co-cultured rat myotubes increased 2-fold as determined by the presence of miniature endplate potentials (MEPPs) in NCS-1-overexpressing NG108-15 cells compared to non- and mock-transfected cells. The number of neurites per cell, branches per neurite and length of neurites was slightly less in cells that were either transiently transfected (GFP-NCS-1-fluorescence positive) or stably transformed with NCS-1 compared to GFP-NCS-1-negative, non-transfected or mock-transfected NG108-15 cells. The number of action potentials that elicited endplate potentials increased in NG108-15 cells stably transformed with rat NCS-1. The mean number of quanta per impulse (m) increased 5-fold. These results show that NCS-1 functions to facilitate synapse formation, probably because of the increased quantal content of evoked acetylcholine release.
 ...
PMID:Overexpression of rat neuronal calcium sensor-1 in rodent NG108-15 cells enhances synapse formation and transmission. 1131 36

We have described, in undifferentiated SH-SY5Y human neuroblastoma cells, the relative potency of Clostridium botulinum neurotoxin (BoNT) serotypes A-F Sensitivity of stimulated [3H]-noradrenaline ([3H]-NA) release to the toxins had a rank order of potency of: C > D > A > B > F after 3 days exposure. The difference between the most potent (BoNT/C: IC50 0.54 nM) and the least (BoNT/F: IC50 > 300 nM) was approximately 1,000-fold. Though fluid phase endocytosis may have been the mechanism of entry for low potency toxins the far higher potency of BoNT/C would suggest receptor-driven entry. Potency was not a reflection of the dependence of the release mechanism on a particular SNARE since the substrate specificities were mixed throughout the potency order. This indicated that the toxins differed in their efficiency of binding/endocytosis or enzymatic activity inside the cell. The serotypes that cleaved vesicle-associated membrane protein (VAMP) isoforms (BoNT/B, D and F) did not fully inhibit [3H]-NA release. Cleavage of the appropriate substrate proteins was observed for all serotypes. SNAP-25 cleavage by BoNT/A was shown to be a dose-dependent and correlated closely with reduction of release, supporting proteolysis as the mechanism by which toxin inhibited secretion. Comparison of the SH-SY5Y cell line sensitivity to BoNT/A with glycine releasing rat primary spinal cord neuron cultures, revealed a massive difference in potency; the primary cultures being approximately 200,000-fold more sensitive. The demonstration, using BoNTs, of the crucial role of SNAP-25, VAMP and syntaxin in SH-SY5Y cells suggests the use of this neuroblastoma as a model in the study of these proteins in neurotransmitter release.
 ...
PMID:Clostridium botulinum neurotoxins act with a wide range of potencies on SH-SY5Y human neuroblastoma cells. 1157 3

SNAP-25 is an integral protein of the plasma membrane involved in neurotransmission and hormone secretion. The cysteine-rich domain of SNAP-25 is essential for membrane binding and plasma-membrane targeting. However, this domain is not required for SNARE complex formation and fusion of membranes in vitro. In this paper, we describe an 'intact-cell'-based system designed to compare the effect of similar amounts of membrane-bound and soluble SNAP-25 proteins on regulated exocytosis. In transfected neuroblastoma cells, Botulinum neurotoxin E (BoNT/E), a protease that cleaves SNAP-25, blocks regulated release of hormone. However, hormone release is rescued by expressing a wild-type SNAP-25 protein resistant to the toxin. BoNT/E-resistant SNAP-25 proteins lacking the cysteine-rich domain or with all the cysteines substituted by alanines do not form SNARE complexes or rescue regulated exocytosis when expressed at the same level as membrane-bound SNAP-25, which is approximately four-fold higher than the endogenous protein. We conclude that the cysteine-rich domain of SNAP-25 is essential for Ca(2+)-dependent hormone release because, by targeting SNAP-25 to the plasma membrane, it increases its local concentration, leading to the formation of enough SNARE complexes to support exocytosis.
 ...
PMID:Plasma membrane targeting of SNAP-25 increases its local concentration and is necessary for SNARE complex formation and regulated exocytosis. 1214 Feb 65

To elucidate the biological differences in neural phenotype between malignant rhabdoid tumor (MRT) and neuroblastoma cell lines, we examined the expression of solube N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex proteins in MRT cell lines under differentiation induction with 12-O-tetradecanoylphorbol-13-acetate (TPA). Six MRT cell lines (TM87-16, STM91-01, TTC642, TTC549, YAM-RTK1, and TTC1240) and six neuroblastoma cell lines (IMR-32, NH12, SCCH26, TGW, NB-1, and NB-NR) were used in this study. Expression of SNAREs: the vesicle SNARE (synaptotagmin, synaptophysin, and synaptobrevin-2) and the target SNARE (syntaxin 1A, SNAP-25A/B) was examined. Our results showed that in MRT cells, only two cell lines (TM87-16, TTC642) expressed the vesicle SNARE and the target SNARE with the exception of SNAP-25B, while all neuroblastoma cells expressed the entire SNARE complex. During differentiation, synaptotagmin was upregulated in these two MRT cell lines. Interestingly, synaptophysin was downregulated in these MRT cell lines in contrast with the neuroblastoma cell lines. SNAP-25B was not expressed in MRT cells after differentiation with TPA. MRT cells having a neural phenotype morphologically looked like neuroblastoma cells after treatment with TPA. However, the expression of SNARE complex was incomplete in MRT cells. Our results suggest that the biological characteristics of MRT cells with neural phenotype are distinct from those of neuroblastoma cells.
 ...
PMID:Malignant rhabdoid tumor shows incomplete neural characteristics as revealed by expression of SNARE complex. 1221 Aug 30

Nitric oxide is well accepted as one of the defenses for inhibiting viral dissemination. Macrophages and cells in the macrophage lineage are professional nitric oxide producers which sub-serve as target for dengue virus. The interaction between nitric oxide and dengue virus in such target cell is unknown. In this report, the impact of nitric oxide on infectious dengue virus serotype 2 production and RNA replication was investigated in vitro. Primary isolates of dengue virus serotype 2 from dengue patients were replicated in mouse neuroblastoma cells in the presence of an exogenous nitric oxide donor, s-nitroso-N-acethylpennicillamine, SNAP, at the concentration of 50 or 75 or 100 microM. Nitric oxide inhibited viral replication in a dose and a multiplicity of infection dependent manner. Nitric oxide from 50 and 75 microM SNAP delayed and suppressed replication of dengue virus isolates while higher concentration of nitric oxide, 100 microM SNAP, completely inhibited production of infectious particles up to 36 hr study. Twenty-four out of forty tested isolates, 60%, were susceptible to 50 microM SNAP inhibitory effect. The mechanism of inhibition was investigated at the level of RNA synthesis and was found that RNA production was suppressed which correlated to production of the infectious particles. Down-regulation of the RNA synthesis resulted in reduction of protein synthesis which was detected by lower level of NS1 protein synthesis using immunoblotting. In conclusion, nitric oxide from exogenous nitric oxide donor down regulated replication of dengue virus serotype 2 isolates from dengue patients. The suppression was clearly shown at the level of viral RNA and protein synthesis resulting in reduction of viral progenies production. This phenomenon implies that nitric oxide may serve as a defense which diminishes viral load in patients.
 ...
PMID:Nitric oxide radical suppresses replication of wild-type dengue 2 viruses in vitro. 1603 50

Caveolins are the main structural proteins of glycolipid/cholesterol-rich plasmalemmal invaginations, termed caveolae. In addition, caveolin-1 isoform takes part in membrane remodelling as it binds and transports newly synthesized cholesterol from endoplasmic reticulum to the plasma membrane. Caveolin-1 is expressed in many cell types, including hippocampal neurons, where an abundant SNAP25-caveolin-1 complex is detected after induction of persistent synaptic potentiation. To ascertain whether caveolin-1 influences neuronal voltage-gated Ca2+ channel basal activity, we stably expressed caveolin-1 into transfected neuroblastoma x glioma NG108-15 hybrid cells [cav1(+) clone] that lack endogenous caveolins but express N-type Ca2+ channels upon cAMP-induced neuronal differentiation. Whole-cell patch-clamp recordings of cav1(+) cells demonstrated that N-type current density was reduced in size by approximately 70% without any significant change in the time course of activation and inactivation and voltage dependence. Moreover, the cav1(+) clone exhibited a significantly increased proportion of membrane cholesterol compared to wild-type NG108-15 cells. To gain insight into the mechanism underlying caveolin-1 lowering of N-current density, and more precisely to test whether this was indirectly caused by caveolin-1-induced enhancement of membrane cholesterol, we compared single N-type channel activities in cav1(+) clone and wild-type NG108-15 cells enriched with cholesterol after exposure to a methyl-beta-cyclodextrin-cholesterol complex. A lower Ca2+ channel activity was recorded from cell-attached patches of both cell types, thus supporting the view that the increased proportion of membrane cholesterol is ultimately responsible for the effect. This is due to a reduction in the probability of channel opening caused by a significant decrease of channel mean open time and by an increase of the frequency of null sweeps.
 ...
PMID:Caveolin-1 expression and membrane cholesterol content modulate N-type calcium channel activity in NG108-15 cells. 1604 Jul 58


1 2 3 Next >>