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 relationship between the depletion of IP3-releasable intracellular Ca2+ stores and the activation of Ca(2+)-selective membrane current was determined during the stimulation of M1 muscarinic receptors in N1E-115 neuroblastoma cells. External Ca2+ is required for refilling Ca2+ stores and the voltage-independent, receptor-regulated Ca2+ current represents a significant Ca2+ source for refilling. The time course of Ca2+ store depletion was measured with fura-2 fluorescence imaging, and it was compared with the time course of Ca2+ current activation measured with nystatin patch voltage clamp. At the time of maximum current density (0.18 + .03 pA/pF; n = 48), the Ca2+ content of the IP3-releasable Ca2+ pool is reduced to 39 + 3% (n = 10) of its resting value. Calcium stores deplete rapidly, reaching a minimum Ca2+ content in 15-30 s. The activation of Ca2+ current is delayed by 10-15 s after the beginning of Ca2+ release and continues to gradually increase for nearly 60 s, long after Ca2+ release has peaked and subsided. The delay in the appearance of the current is consistent with the idea that the production and accumulation of a second messenger is the rate-limiting step in current activation. The time course of Ca2+ store depletion was also measured after adding thapsigargin to block intracellular Ca2+ ATPase. After 15 min in thapsigargin, IP3-releasable Ca2+ stores are depleted by > 90% and the Ca2+ current is maximal (0.19 + 0.05 pA/pF; n = 6). Intracellular loading with the Ca2+ buffer EGTA/AM (10 microM; 30 min) depletes IP3-releasable Ca2+ stores by between 25 and 50%, and it activates a voltage-independent inward current with properties similar to the current activated by agonist or thapsigargin. The current density after EGTA/AM loading (0.61 + 0.32 pA/pF; n = 4) is three times greater than the current density in response to agonist or thapsigargin. This could result from partial removal of Ca(2+)-dependent inactivation.
J Gen Physiol 1995 Nov
PMID:The relationship between depletion of intracellular Ca2+ stores and activation of Ca2+ current by muscarinic receptors in neuroblastoma cells. 864

Tacrine [9-amino-1,2,3,4-tetrahydroacridine] (THA), a potent acetylcholinesterasic inhibitor, is utilized in the pharmacological treatment of Alzheimer's disease (Birne and Arie, 1994). Cytopharmacology of THA is still largely to be discovered. In the present paper we report some effects produced by THA on murine neuroblastoma cells (N2A) used as an experimental model. N2A cells treated with THA at low concentration (1 mu M) showed a reduced cell's mitosis and a remarkable reduction of protein synthesis. Eventually, a marked reduction on the phosphorylation of proteins associated to neurofilaments 200 kD, is observed using specific antibody.
J Neural Transm Gen Sect 1995
PMID:Effects of tacrine upon murine neuroblastoma cells. 874 76

We have isolated and characterized the 5'-flanking region and the proximal polyadenylation site of the human 5-HT transporter gene. The major gene transcript is 2,793 bp in length and it contains 208 bp of 5'-untranslated region (5'-UTR) and 694 bases of 3'-UTR. While only a single mRNA species occurs in rats and mice, the most proximal signal for polyadenylation in the human gene appears to be highly degenerate in comparison to the rat and murine motif. This polyadenylation signal-like motif may lead to alternate usage of additional polyadenylation sites resulting in multiple mRNA species in humans. A TATA-like motif and several potential binding sites for transcription factors including AP1, AP2, SP1, and a cAMP response element (CRE)-like motif are present in the 5'-flanking region. A approximately 1.7 kb fragment beginning 217 bp downstream from the transcription start site, which had been ligated into a luciferase reporter vector and transiently expressed in JAR human placental choriocarcinoma cells, displayed both constitutive and forskolin/cholera toxin-induced promoter activity. Functional promoter mapping revealed that there are negative attenuating elements between bp -1,428 and -1,185 and positive elements between bp -1,184 and -78 from the transcription initiation site. Studies with deletional mutants also indicated that core promoter sequences are contained within 78 bp of the transcription start site and that regulation of cAMP-inducible promoter activity depends on multiple cis-acting elements including two AP1 binding sites and a single CRE-like element located at bp -99. Our findings suggest that (1) the 5-HT transporter gene promoter is active in human JAR cells, but inactive in 5-HT transporter-deficient human SK-N-SH neuroblastoma and HeLa cells, (2) the information contained within 1.4 kb of 5'-flanking sequence is sufficient to confer its cell-specific expression, (3) the promoter responds to cAMP induction, and (4) the expression of the 5-HT transporter gene is regulated by a combination of positive and negative cis-acting elements operating through a basal promoter unit defined by a TATA-like motif.
J Neural Transm Gen Sect 1995
PMID:Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene. 878 73

Using a CD4-capture immunoassay for gp120, several strains of human immunodeficiency virus type 1 (HIV-1) grown in CD4-expressing T lymphoblastoid cells were found to contain little CD4-reactive gp120 (0.3-1.0 ng/ml) relative to virus titre (10(3.2)-10(5.0) TCID50/ml) and p24 antigen (80-1000 ng/ml). The measured CD4-reactive gp120 concentrations of HIV-1 suspensions grown in CD4-negative human neuroblastoma cells were 100- to 10,000-fold greater than those of HIV-1 grown in CD4-positive lymphoblastoid cells, even though both virus suspensions contained abundant viral gp120 as shown by immunoblot assay. It was postulated that CD4 derived from host cells might be associated with virions, concealing the binding domains of gp120. CD4 association with HIV-1 virions grown in CD4-positive cells was demonstrated directly by immunoblot assay of sucrose gradient-purified virus suspensions and by specific co-sedimentation of 125I-labelled OKT4 with virions propagated in CD4-expressing cells. CD4 coating of primary HIV-1 isolates grown in peripheral blood mononuclear cells was also observed. The biological significance of CD4 coating of HIV particles remains to be determined.
J Gen Virol 1996 Sep
PMID:Human immunodeficiency virus grown in CD4-expressing cells is associated with CD4. 881 Sep 98

1. A human neuroblastoma cell line, SH-SY5Y, was used to determine the effects of delta-9-tetrahydrocannabinol (THC) on microtubule-associated tau protein. 2. After 48-hr treatment, THC (10(-9) M) decreased 50 kD tau protein in the cytoplasmic (supernatant) fraction, and in the membrane (pellet) fraction the drug (10(-7) M) also decreased 50 kD tau protein. 3. This reduction in tau protein was accompanied by a 27% reduction (P < 0.05) in the membrane (pellet) total protein after (10(-7) M) THC and a 28% increase (P < 0.02) in cytoplasmic (supernatant) total protein after 10(-9) M THC.
Gen Pharmacol 1996 Oct
PMID:Tau protein after delta-9-tetrahydrocannabinol in a human neuroblastoma cell line. 898 Oct 58

Variants of the prototype Murray Valley encephalitis virus (MVE-1-51) were selected by serial plaque purification and amplification in monkey kidney (Vero) cells. Four clones (C1-C4) at passage levels two and nine (P2 and P9) were examined in 21-day-old Swiss outbred mice for neuroinvasiveness (assessed from LD50 values after intraperitoneal inoculation) and neurovirulence (LD50 values after intracranial inoculation). The growth characteristics of the clones were determined in intracranially inoculated mouse brain and in mouse neuroblastoma, Vero and mosquito (C6/36) cell lines. Genomic RNA of the cloned virus stocks was sequenced through the structural protein genes (E, prM/M and C) and the 5' untranslated region. Clone C2P2 was of high neuroinvasiveness whereas C2P9 was of low neuroinvasiveness; there were also decreased yields of C2P9 in C6/36 cells compared to C2P2 and MVE-1-51. These changes were associated with the substitution of valine for phenylalanine at amino acid position 141 of the C2P9 E protein. Clone C4P2 was of high neurovirulence and low neuroinvasiveness; C4P9 was of low neurovirulence, a change accompanied by a further reduction in neuroinvasiveness. Concomitantly, C4P9 showed a pronounced reduction in growth rates and yields in 21-day-old Swiss mouse brain, in mouse neuroblastoma cells and in C6/36 cells compared to parental virus. The phenotypic changes in clone 4 appear to be due to mutation(s) within non-structural protein genes.
J Gen Virol 1995 Apr
PMID:Neurovirulence and neuroinvasiveness of Murray Valley encephalitis virus mutants selected by passage in a monkey kidney cell line. 904 32

Malignant ectomesenchymoma is a rare soft tissue tumor of the childhood believed to arise from a remnant of pluripotential migratory neural crest cell (ectomesenchym) and composed of both a mesenchymal element (most often embryonal rhabdomyosarcoma) and a neuroectodermal element (ganglioneuroma, schwanomma neuroblastoma or melanocytic cells). Reported sites of origin are the abdomen, perineum or scrotum, the extremities, the middle ear, nasopharynx, face, and neck. Herein we report a new case of an orbital ectomesenchymoma studied by means of histochemistry and immunohistochemistry in order to increase the morphologic and histogenetic knowledge of this peculiar tumor and its significance concerning the differential diagnosis.
Gen Diagn Pathol 1997 Feb
PMID:Primary malignant ectomesenchymoma of the orbit. 906 87

The relative permeability sequences of the rat connexin 43 (rCx43) gap junction channel to seven cations and chloride were examined by double whole cell patch clamp recording of single gap junction channel currents in rCx43 transfected neuroblastoma 2A (N2A) cell pairs. The measured maximal single channel slope conductances (gammaj, in pS) of the junctional current-voltage relationships in 115 mM XCI were RbC1 (103) > or = CsC1 (102) > KC1 (97) > NaC1 (79) > or = LiC1 (78) > TMAC1 (65) > TEAC1 (53) and for 115 mM KY were KBr (105) > KC1 (97) > Kacetate (77) > Kglutamate (61). The single channel conductance- aqueous mobility relationships for the test cations and anions were linear. However, the predicted minimum anionic and cationic conductances of these plots did not accurately predict the rCx43 channel conductance in 115 mM KC1. Instead, the conductance of the rCx43 channel in 115 mM KC1 was accurately predicted from cationic and anionic conductance-mobility plots by applying a mobility scaling factor Dx/Do, which depends upon the relative radii of the permeant ions to an estimated pore radius. Relative permeabilities were determined for all of the monovalent catious and anions tested from asymmetric salt reversal potential measurements and the Goldman-Hodgkin-Katz voltage equation. These experiments estimate the relative chloride to potassium permeability to be 0.13. The relationship between the relative cation permeability and hydrated radius was modeled using the hydrodynamic equation assuming a pore radius of 6.3 +/- 0.4 A. Our data quantitatively demonstrate that the rCx43 gap junction channel is permeable to monovalent atomic and organic cations and anions and the relative permeability sequences are consistent with an Eisenman sequence II or I, respectively. These predictions about the rCx43 channel pore provide a useful basis for future investigations into the structural determinants of the conductance and permeability properties of the connexin channel pore.
J Gen Physiol 1997 Apr
PMID:Monovalent ion selectivity sequences of the rat connexin43 gap junction channel. 910 7

The unitary conductances and permeability sequences of the rat connexin40 (rCx40) gap junction channels to seven monovalent cations and anions were studied in rCx40-transfected neuroblastoma 2A (N2A) cell pairs using the dual whole cell recording technique. Chloride salt cation substitutions (115 mM principal salt) resulted in the following junctional maximal single channel current-voltage relationship slope conductances (gamma 1 in pS): CsC1 (153), RbC1 (148), KC1 (142), NaC1 (115), LiC1 (86), TMAC1 (71), TEAC1 (63). Reversible block of the rCx40 channel was observed with TBA. Potassium anion salt gamma j are: Kglutamate (160), Kacetate (160), Kaspartate (158), KNO3 (157), KF (148), KC1 (142), and KBr (132). Ion selectivity was verified by measuring reversal potentials for current in rCx40 gap junction channels with asymmetric salt solutions in the two electrodes and using the Goldman-Hodgkin-Katz equation to calculate relative permeabilities. The permeabilities relative to Li+ are: Cs+ (1.38), Rb+ (1.32), K+ (1.31), Na+ (1.16), TMA+ (0.53), TEA+ (0.45), TBA+ (0.03), Cl- (0.19), glutamate+ (0.04), and NO(3)- (0.14), assuming that the monovalent anions permeate the channel by forming ion pairs with permeant monovalent cations within the pore thereby causing proportionate decreases in the channel conductance. This hypothesis can account for why the predicted increasing conductances with increasing ion mobilities in an essentially aqueous channel were not observed for anions in the rCx40 channel. The rCx40 effective channel radius is estimated to be 6.6 A from a theoretical fit of the relationship of relative permeability and cation radius.
J Gen Physiol 1997 Apr
PMID:Monovalent cation permeation through the connexin40 gap junction channel. Cs, Rb, K, Na, Li, TEA, TMA, TBA, and effects of anions Br, Cl, F, acetate, aspartate, glutamate, and NO3. 910 8

The stimulation of IP3 production by muscarinic agonists causes both intracellular Ca2+ release and activation of a voltage-independent cation current in differentiated N1E-115 cells, a neuroblastoma cell line derived from mouse sympathetic ganglia. Earlier work showed that the membrane current requires an increase in 3',5'-cyclic guanosine monophosphate (cGMP) produced through the NO-synthase/guanylyl cyclase cascade and suggested that the cells may express cyclic nucleotide-gated ion channels. This was tested using patch clamp methods. The membrane permeable cGMP analogue, 8-br-cGMP, activates Na+ permeable channels in cell attached patches. Single channel currents were recorded in excised patches bathed in symmetrical Na+ solutions. cGMP-dependent single channel activity consists of prolonged bursts of rapid openings and closings that continue without desensitization. The rate of occurrence of bursts as well as the burst length increase with cGMP concentration. The unitary conductance in symmetrical 160 mM Na+ is 47 pS and is independent of voltage in the range -50 to +50 mV. There is no apparent effect of voltage on opening probability. The dose response curve relating cGMP concentration to channel opening probability is fit by the Hill equation assuming an apparent KD of 10 microm and a Hill coefficient of 2. In contrast, cAMP failed to activate the channel at concentrations as high as 100 microm. Cyclic nucleotide gated (CNG) channels in N1E-115 cells share a number of properties with CNG channels in sensory receptors. Their presence in neuronal cells provides a mechanism by which activation of the NO/cGMP pathway by G-protein-coupled neurotransmitter receptors can directly modify Ca2+ influx and electrical excitability. In N1E-115 cells, Ca2+ entry by this pathway is necessary to refill the IP3-sensitive intracellular Ca2+ pool during repeated stimulation and CNG channels may play a similar role in other neurons.
J Gen Physiol 1997 Aug
PMID:Cyclic GMP-gated channels in a sympathetic neuron cell line. 923 8


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