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 present paper reports how aluminium [Al(III)] at a concentration of 3.7 microM can activate the bovine erythrocytic enzyme acetylcholinesterase (AChE) by about 38% in vitro. This same activating effect was observed on AChE form human as well as from rat erythrocyte ghosts and murine neuroblastoma cells. The interaction between Al3+ and gamma-peripheral sites of the enzyme produces AChE structural modifications as evidenced by circular dichroism measurements. This may provide a molecular explanation of the raised enzymatic activity.
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PMID:Activation of acetylcholinesterase by aluminium(III): the relevance of the metal species. 782 30

Phenylacetate, a natural metabolite of phenylalanine which was originally described as a plant growth hormone, has recently gained attention as a possible differentiation inducer for a variety of human tumor cell types. This interest prompted us to assess the ability of sodium phenylacetate (NaPA) to promote the differentiation of human neuroblastoma cells, both alone and in combination with retinoic acid (RA), a known inducer of neuroblastoma differentiation and maturation. Using the LA-N-5 cell line, we have determined that NaPA can stimulate the differentiation of neuroblastoma cells, as evidenced by dose-dependent inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity and reduction of N-myc expression. Furthermore, NaPA and RA synergized in inducing differentiation, in that combination treatment resulted in cessation of cell growth along with morphologic and biochemical changes indicative of the loss of malignant properties. We have determined that NaPA can markedly enhance mRNA levels of the nuclear RA receptor-beta (RAR beta) in LA-N-5 cells prior to morphologic or other phenotypic changes induced by this compound. This effect appeared to be distinct from the ability of NaPA to alter tumor cell lipid metabolism via inhibition of protein isoprenylation. Thus among its varied effects on LA-N-5 cells, NaPA appears to interact with the RA pathway at the nuclear level by up-regulating RAR beta expression.
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PMID:Phenylacetate synergizes with retinoic acid in inducing the differentiation of human neuroblastoma cells. 782 65

In the human neuroblastoma cell line LA-N-2, recombinant rat ciliary neurotrophic factor (CNTF) induced neurite growth and cholinergic differentiation that were both half-maximally saturated at < 100 pM of the neurokine, but was not required for cell survival in serum-free conditions over a 13-day period. CNTF markedly stimulated choline acetyltransferase activity and acetylcholine synthesis, whereas high-affinity choline transport was only slightly enhanced and acetylcholinesterase activity was unchanged. Leukemia inhibitory factor had effects identical to CNTF on neurite growth and choline acetyltransferase activity, but interleukin 6 had no effect. Radioiodinated CNTF binding and affinity cross-linking studies were consistent with tripartite receptor activation as a mediator of the observed biological effects.
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PMID:Differentiation effects of ciliary neurotrophic factor on human neuroblastoma cells. 789 Oct 74

We have observed that cultured neurons from chick spinal cord and the neuroblastoma hybrid line 108CC15 released lower amounts of acetylcholinesterase (AChE) when compared with the parental line, N18TG2. AChE activity extracted by hypotonic buffer, which can be regarded as the source of the released enzyme, was considerably higher in the parental than in the hybrid 108CC15 (respectively, approximately 80% and approximately 40% of cellular activity). On the other hand, evaluation of ectocellular, with respect to total, AChE activity showed that in N18TG2 cells only 7% of AChE was localized on the plasmalemma, whereas in the hybrid line the percentage of ectocellular activity was 3.7 times higher than in the parental line. We have also examined the effect of cytochalasin B and nocodazole. In the N18TG2 line, the former did not affect AChE release, which was significantly reduced by the latter. High K+ level in the culture medium, of both N18TG2 and hybrid 108CC15 cultures, induced an increase in AChE secretion; Ca2+ presence was required for high K(+)-induced release. Muscle extracts increased AChE secretion in both the hybrid 108CC15 and the spinal cord neurons. The present data suggest that AChE secretion during neuronal development is modulated by depolarizing stimuli and by soluble factors produced by target cells and may be involved in the control of neuronal differentiation.
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PMID:Characterization of acetylcholinesterase secretion in neuronal cultures and regulation by high K+ and soluble factors from target cells. 789 Oct 79

The toxic effects of arsenic at different cellular levels were assessed using two inorganic chemical species: sodium arsenite and sodium arsenate, representing the trivalent and pentavalent states of arsenic, respectively. Mouse neuroblastoma cell cultures (Neuro-2a) were exposed for 24 h, and cytotoxic effects evaluated were: cell proliferation by quantification of total protein content; cytoplasmic membrane integrity to cytosolic lactate dehydrogenase leakage; lysosomal hexosaminidase release; lactate dehydrogenase activity; mitochondrial succinate dehydrogenase activity; relative neutral red uptake by lysosomes; lysosomal hexosaminidase sphingolipid degradation activity; and acetylcholinesterase activity. As(III) was found to be five times more toxic than As(V) to neuroblastoma cell proliferation, but the relative extent of other alterations differed. Special sensitivity was detected for lactate dehydrogenase inhibition. Hexosaminidase activity was also very susceptible, being inhibited at low concentrations and stimulated at high concentrations. Less sensitive were the inhibition of cell proliferation, relative neutral red uptake, and acetylcholinesterase activity. As(III) was lysosomotropic, with secretion of hexosaminidase, but the release was decreased by As(V). Mitochondrial succinate dehydrogenase was inhibited by As(III) and stimulated by As(V). Minor sensitivity to cytoplasmic lactate dehydrogenase leakage for both compounds also shows that functional metabolic alterations produced by arsenic are more important than structural damage.
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PMID:Comparative in vitro effects of sodium arsenite and sodium arsenate on neuroblastoma cells. 794 May 56

The effects of either radiation or hyperthermia on the differentiation potential of NG108-15, a neuroblastoma-glioma hybrid cell line, were studied. After radiation and hyperthermia, the outgrowth of neurites from NG108-15 cells was potentiated, and polarizing current and voltage pulses induced a distinct action potential and a diphasic (inward following outward) current, respectively. An increase in the specific activity of acetylcholinesterase was also observed. In addition, both treatments induced an elevation of the concentration of intracellular calcium in some cells. The increase in intracellular calcium concentration caused by applying the calcium ionophore, A23187, induced differentiation. It is suggested that both the radiation- and the hyperthermia-induced increases of electrical excitability and acetylcholinesterase activity may have originated from an increase in intracellular Ca2+ concentration.
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PMID:Induction of differentiation by radiation and hyperthermia in neuroblastoma-glioma hybrid cells. 804 90

The characteristic features of Alzheimer's disease (AD) include a high density of beta-amyloid-containing plaques in the cerebral cortex and the loss of basal forebrain cholinergic neurons. Amyloid beta-protein (A beta, Mr. approximately 4.5 kDa) is derived from a family of large (Mr. approximately 110-140 kDa) beta-amyloid precursor proteins (APP) which are integral membrane glycoproteins consisting of a large extracytoplasmic domain, a transmembrane domain, and a short cytoplasmic tail. Secreted derivatives of APP lacking the cytoplasmic tail, transmembrane domain, and a small portion of the extracellular domain are generated by the proteolytic processing of full length APP by a family of proteolytic enzymes known as APP secretases. Using cell cultures, we investigated the possibility that APP processing can be regulated by a centrally active cholinesterase inhibitor, tacrine, which has recently been shown to improve memory and cognitive functions in patients with AD. We analyzed the level of APP in glial, fibroblast, pheochromocytoma (PC12), and neuroblastoma cells by immunoblotting cell lysates and conditioned media. Normal levels of secretion of soluble APP derivatives by cells into conditioned media were severely inhibited by treating cells with tacrine. A similar decrease after treatment with tacrine was observed when neuroblastoma and PC12 cells were pretreated with either growth factors, phorbol ester, or retinoic acid. To determine whether the effect of tacrine on APP levels was specific or a more general phenomenon affecting other proteins, we measured the level of heat shock protein-70 (HSP-70) and another secretory protein, protease nexin-1 (PN-1). Tacrine treatment did not alter the level of HSP-70 in cell extracts and tacrine affected mildly the secretion of PN-1. Thus, the processing of HSP and PN-1, unlike APP, was not severely affected by treating cells with tacrine. Our results suggest that tacrine may inhibit an acetylcholinesterase-associated proteolytic activity involved in the secretion of APP, which results in less secretion of soluble APP into the conditioned media from tacrine treated cells. These results demonstrate that tacrine regulates APP secretion in cell cultures and suggest the possibility that tacrine therapy of Alzheimer's disease may, in the longer term, have effects on the process of A beta deposition.
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PMID:Tacrine alters the secretion of the beta-amyloid precursor protein in cell lines. 804 78

To determine the functions of the alpha 1 and beta 1 thyroid hormone receptors (TRs) in neural differentiation, we have established stable transfected neuronal cell lines (Neuro-2a) that overexpress either TR alpha 1 or TR beta 1. 3,5,3'-Triiodothyronine (T3) treatment of cells that overexpress TR beta 1 blocks proliferation by an arrest of cells in G0/G1 and induces morphological and functional differentiation of Neuro-2a cells as indicated by the marked increase in the number of perisomatal filopodia-like neurites and in acetylcholinesterase (AChE) activity. The effect on AChE activity was dose-dependent, and the time-course analysis reveals that this effect occurs after 24 hr of T3 treatment, with a maximal increase occurring after 48 hr of treatment. The increase of AChE activity is paralleled by an increase of AChE mRNAs. Last, we present evidence that shows that the effects of T3 on differentiation are independent of its effect on proliferation. T3 had no effect on the differentiation of Neuro-2a cells that overexpressed TR alpha 1. Our results indicate that TR beta 1 may play a key role in the effects of T3 in neuroblastoma cell differentiation.
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PMID:Overexpression of the beta 1 thyroid receptor induces differentiation in neuro-2a cells. 814 69

In cultured human neuroblastoma cells (SK-N-MC), a plasma membrane-bound besides a lysosomal ganglioside GM3 sialidase was detected. Both activities can be distinguished by the specific activation with detergents, as well as differential inhibition by Cu++. Plasma membrane and lysosomal sialidase specific activities showed strikingly different behaviour during the growth phase of neuroblastoma cells. Thus, the plasma membrane sialidase increased about 15-fold and mirrored cell growth, it differed from the kinetics of ornithine decarboxylase, an early marker of cell proliferation. The lysosomal sialidase, on the other hand, exhibited constant specific activities during growth of the cells, as did lysosomal and plasma membrane marker enzymes. When the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid was included in the culture medium, a profound change in proliferation kinetics was observed, indicating a release from density-dependent control of cell division. Additionally, the inhibitor abolished the increase of the biochemical differentiation marker acetylcholinesterase. The results suggest an important role of the ganglioside sialidase of the plasma membrane in the processes of proliferation control and differentiation in this neuronal cell system.
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PMID:Role of plasma membrane ganglioside sialidase of human neuroblastoma cells in growth control and differentiation. 814 59

Cholinergic neurons in PNS and CNS are identified by the presence of choline acetyltransferase and the accumulation of choline by a high-affinity, sodium-coupled choline transporter to be used for acetylcholine synthesis. It appears that expression of choline acetyltransferase can be altered by several physiological conditions, including hormones and trophic factors, but little is known about control of expression of the sodium-coupled choline carrier or whether these two phenotypic markers are regulated similarly. In the present study, the cholinergic human neuroblastoma LA-N-2 was used to investigate regulation of expression of choline acetyltransferase and choline uptake activity associated with differentiation and neurite extension. Cells grown in serum-containing basal medium maintained a relatively undifferentiated morphology, expressed low levels of choline acetyltransferase activity, and accumulated choline by a sodium-dependent process followed by conversion to acetylcholine. Transfer of cells to an enriched, serum-free defined medium resulted in morphological and neurochemical differentiation, with an enhancement of cholinergic phenotype. Hemicholinium-sensitive choline uptake activity was increased about sixfold over a 4-day period, with no change in choline acetyltransferase or acetylcholinesterase specific activity. Acetylcholine synthesis was increased in parallel with the changes in choline accumulation; choline metabolism in the differentiated cells differed significantly from that observed in the undifferentiated cells, with proportionally less converted to phosphorylcholine and proportionally more remaining as unmetabolized choline and converted to acetylcholine. The enhanced choline accumulation appeared to be mediated by an increased number of choline carriers, demonstrated by increased binding of the affinity ligand [3H]-choline mustard to the transporter and by an increased Vmax for the uptake process. The increased expression of the transport function appeared to be under transcriptional control, as the enhancement of uptake was blocked by the RNA polymerase II inhibitor alpha-amanitin as well as by the protein synthesis inhibitor cycloheximide. These results show that expression of sodium-coupled choline carriers and choline acetyltransferase may be regulated separately in the differentiating neuroblastoma LA-N-2 and that neurotransmitter synthesis is controlled by provision of precursor rather than at the level of the biosynthetic enzyme.
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PMID:Regulation of expression of cholinergic neuronal phenotypic markers in neuroblastoma LA-N-2. 837 93


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