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)

Two clonal immortalized neurons designated CL8c4.7 and CL8a5.2 were established by somatic cell fusion between a hypoxanthine phosphoribosyltransferase-(HPRT-) deficient neuroblastoma N18TG2 and newborn mouse cerebellar/brain stem neurons. In the serum-containing medium without extra differentiating agents, both clones exhibited a morphology of differentiated neurons. They contained high levels of glutamate but no gamma-aminobutyric acid (GABA). The CL8a5.2 clone synthesized choline acetyltransferase and serotonin. In immunocytochemical studies, both clones expressed 200 kD neurofilament protein, neuron-specific enolase, microtubule-associated protein 2 (MAP2), tau protein, neuronal cell adhesion molecule (N-CAM), HNK-1, Thy-1.2, saxitoxin-binding sodium channel protein, and glutamate. Synaptophysin immunoreactivity was identified in the neuritic terminals of CL8c4.7 cells. Most of these antigens were barely detectable on N18TG2 cells. Electrophysiologically, both clones generated action potentials in response to electrical stimuli. The hybrid clones that express characteristics of differentiated neurons derived from the cerebellar and brain stem regions might be invaluable for the study of the molecular basis of neuronal differentiation and degeneration in these regions.
 ...
PMID:Establishment of mouse-immortalized hybrid clones expressing characteristics of differentiated neurons derived from the cerebellar and brain stem regions. 135 6

NB2a/d1 neuroblastoma cells constitutively express multiple isoforms of the microtubule-associated protein tau and incorporate this protein into the axonal neurites elaborated during serum deprivation. To examine whether or not tau played an essential role in axonal outgrowth, cells cultured in serum-free medium were treated at 24 h intervals with antisense- and sense-oriented cDNA oligonucleotides (25 or 36 mers that span or are upstream of tau initiation codon) and were simultaneously serum deprived. Oligonucleotide uptake was confirmed by determination of intracellular levels of radiolabeled oligonucleotides. Treatment for 48 h with tau antisense oligonucleotides reversibly inhibited the expression of tau and the number of neurite-bearing cells compared with treatment with sense oligonucleotides. By contrast, tubulin expression was not affected. When cells were treated with antisense oligonucleotide simultaneously with serum deprivation, the initial outgrowth of neurites was unaffected, but continued neurite elongation was prevented. By contrast, neurite outgrowth at 4 h was inhibited when cells were pretreated with tau antisense 24 h before serum deprivation. Furthermore, intracellular delivery of anti-tau antiserum prevented neurite outgrowth and, in cells that had previously been deprived of serum for 24 h, induced retraction of existing neurites. These findings indicate that both the initiation and the continued outgrowth of neurites are dependent on tau and that pre-existing cytoplasmic pools of tau can mediate initial neuritogenesis.
 ...
PMID:Microtubule-associated protein tau is required for axonal neurite elaboration by neuroblastoma cells. 143 85

1. SH-SY5Y, a human neuroblastoma cell line, was used as a tissue culture model to examine the hypothesis that cocaine may affect the metabolism of tau protein which stabilizes microtubules and promotes microtubule assembly. 2. Cocaine hydrochloride (10(-9)-10(-3) M) caused dose-dependent reductions in cell number, with 10(-3) M causing 28% reduction after 48 hr. 3. This drug also decreased tau protein (50 Kd) in the cytoplasmic (supernatant) as well as the membrane (pellet) fraction after 48-hr treatment.
 ...
PMID:Microtubular tau protein after cocaine in cultured SH-SY5Y human neuroblastoma. 148 20

1. A human neuroblastoma cell line, SH-SY5Y, was used to study the effects of phencyclidine (PCP) on microtubule-associated tau protein, which acts in vivo chiefly to induce the assembly of tubulin and in vitro to promote microtubule polymerization. 2. PCP (1.0 mM) decreased tau protein (50 kD) in the cytoplasmic (supernatant) fraction as well as in the membrane (pellet) fraction. 3. These changes in tau protein were accompanied by decreases of 30-95% in cell number after concentrations of PCP, 0.25-1.0 mM, respectively. 4. After 0.5 mM PCP cytoplasmic and membrane fractions of SH-SY5Y cells showed 100 and 84% increases in total protein, respectively.
 ...
PMID:Changes in microtubule-associated tau protein in human neuroblastoma cells after phencyclidine. 151 52

Morphological differentiation of N2A neuroblastoma cells is associated with an altered splicing of the gene of the microtubule-associated protein, tau. Two populations of RNA (coding for tau proteins containing three or four tubulin-binding motifs) are present in a similar proportion in undifferentiated neuroblastoma cells while in differentiated cells the proportion is changed in favour of that population coding for tau protein containing four tubulin-binding motifs. An increase in a high molecular weight tau isoforms correlates with the increase in the RNA population coding for four tubulin-binding motifs. A possible consequence of expressing a higher proportion of the tau protein containing four tubulin-binding motifs could be an increase in microtubule stability of differentiated neuroblastoma cells.
 ...
PMID:Differentiation of neuroblastoma cells correlates with an altered splicing pattern of tau RNA. 154 66

The direct effects of the neurotransmitter serotonin on the catecholaminergic enzyme, tyrosine hydroxylase and the microtubule-associated tau protein were studied in a human neuroblastoma cell line. Undifferentiated LAN-5 cells, cultured in serum supplemented basal medium, or cells induced to differentiate by 6 day exposure to 10 uM retinoic acid were treated for 48 hr with 50 nM and 50 uM serotonin. In undifferentiated cells, serotonin treatment (50 uM) decreased both tyrosine hydroxylase activity and a 50 kD cytoplasmic fraction tau protein while 50 nM serotonin treatment caused this 50 kD protein to increase in the cytoplasmic fraction but decrease in the membrane fraction. While basal tyrosine hydroxylase activity increased in differentiated vs. undifferentiated cells, serotonin treatment had no effect on the enzyme or tau in differentiated LAN-5. This study shows serotonin to have direct effects on the biochemistry and cytoskeleton of undifferentiated cultured human neuroblastoma.
 ...
PMID:Effects of serotonin on tyrosine hydroxylase and tau protein in a human neuroblastoma cell line. 168 52

A number of studies have implicated aluminium as a possible factor in the pathogenesis of Alzheimer's disease (AD). Following an examination of the uptake of aluminium by human neuroblastoma cells in culture, treated with a range of concentrations of aluminium complexed with ethylene-diaminetetra-acetic acid (EDTA), we have now carried out an immunocytochemical study. Using an antibody to phosphorylated tau protein, which reacts specifically with AD neurofibrillary tangles (NFT), we have found that after treatment periods of 16 days to 8 weeks with aluminium-EDTA, the cells show positive staining with this antibody. No such reaction was detected in cells grown in medium alone, nor in aluminium-EDTA-treated cells subjected to the same immunocytochemical procedure but without added primary antibody. Cells grown in medium plus EDTA, which contains a low level of aluminium contamination, showed a slight reaction. Our system may provide a suitable model for studying the early changes which lead to NFT formation.
 ...
PMID:Human neuroblastoma cells treated with aluminium express an epitope associated with Alzheimer's disease neurofibrillary tangles. 170 74

The microtubule-associated protein tau, and the cytoplasmic protein ubiquitin, are constituents of pathological neurofibrillary tangles found in Alzheimer's disease. In order to see if there is any physiological relationship between these proteins in a functioning human system, human neuroblastoma (LAN-5) cells were grown in vitro and differentiated to a neuronal phenotype. Cell extracts were analyzed by SDS-PAGE, immunoblot, and immunoprecipitation techniques. The colocalization of ubiquitin and tau immunoreactivity was noted in 12- and 35-kDa bands, predominantly located in a cell membrane fraction. The bands were also isolated by immunoprecipitation with the Alz-50 antibody and then identified with a ubiquitin antiserum. These findings show a relationship between tau and ubiquitin in a human neural cell line. This interaction suggests that tau may normally be degraded by an ubiquitin-dependent mechanism and alterations in it may contribute to the formation of neuro-fibrillary pathology.
 ...
PMID:Tau-ubiquitin protein conjugates in a human cell line. 172 70

The presence of the trivalent metallic cations, aluminum and boron, in the culture medium of differentiated human LAN-5 neuroblastoma cells results in increased amounts of specific isomers of microtubule-associated tau proteins. The cells were differentiated to a neuronal phenotype by the addition of retinoic acid. Six-day exposures of the differentiated cells to a 1-mM dose of aluminum or boron yielded increases in tau protein immunoreactivity to the monoclonal antibodies Tau-1 and Alz-50. Significant increases in immunoreactivity were seen at treatment levels of aluminum down to 100 microM. The increases in tau proteins were independent from increases in levels of total cell protein. Control cultures treated with the divalent cations zinc and iron showed no increases in levels of tau proteins.
 ...
PMID:Effects of aluminum on tau proteins in human neuroblastoma cells. 195 63

The axonal microtubule-associated protein, tau, is thought to play an important role in axonal growth and in the establishment of neuronal polarity. In adult human brain there are six alternatively spliced tau isoforms, which have different microtubule binding affinities in vitro. The tubulin-tau interaction is further modified by phosphorylation of tau and, compared to adult brain tau, both foetal brain tau and paired helical filament (PHF) tau, characteristic of Alzheimer's disease, are hyperphosphorylated. In vivo both the expression of tau isoforms and their phosphorylation states are developmentally regulated. In order to establish the correlation between the expression of tau isoforms and their pattern of phosphorylation, we have characterised these two features in several in vitro models of neuronal differentiation, including the human neuroblastoma cell lines, SK-N-SH, SH-SY5Y and IMR32 cells, rat PC12 cells and primary rat cortical neurones. Sensitive RT-PCR analysis revealed a different complement of tau isoforms in the different cell lines and neuritogenesis was associated mainly with an increase in the overall tau protein level with no apparent phosphorylation changes. A switch in tau isoform expression occurred only at the terminal stages of neuronal development, when it may be important in reinforcing the previously established axonal cytoarchitecture.
 ...
PMID:Tau isoform expression and phosphorylation state during differentiation of cultured neuronal cells. 749 9


1 2 3 4 5 6 7 8 9 10 Next >>