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

Neurotoxicity of long-term exposure to lead, aluminum and cadmium has been studied in vitro on the human neuroblastoma cell line IMR32 by measuring cytotoxicity, and the effects on neuronal-specific characteristics such as nitrite outgrowth and expression of cholinergic receptors as parameters of toxicity. Cytotoxicity was highest with cadmium, intermediate with lead and lowest with aluminum exposure. Lead, but not cadmium and aluminum, interfered with neurite growth. The expression of alpha-bungarotoxin binding sites and muscarinic receptors was markedly increased by cadmium and not affected by aluminum exposure. Lead induced only an increase of toxin binding sites. These in vitro modifications are discussed in relation to the possible use of neuronal cell lines for detecting neurotoxic effects of heavy metals.
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PMID:Effects of long-term in vitro exposure to aluminum, cadmium or lead on differentiation and cholinergic receptor expression in a human neuroblastoma cell line. 350 65

Effects of Pb and several other metal ions on various distinct types of voltage-, receptor- and Ca-activated ion channels have been investigated in cultured N1E-115 mouse neuroblastoma cells. Experiments were performed using the whole-cell voltage clamp and single-channel patch clamp techniques. External superfusion of nanomolar to submillimolar concentrations of Pb causes multiple effects on ion channels. Barium current through voltage-activated Ca channels is blocked by micromolar concentrations of Pb, whereas voltage-activated Na current appears insensitive. Neuronal type nicotinic acetylcholine receptor-activated ion current is blocked by nanomolar concentrations of Pb and this block is reversed at micromolar concentrations. Serotonin 5-HT3 receptor-activated ion current is much less sensitive to Pb. In addition, external superfusion with micromolar concentrations of Pb as well as of Cd and aluminum induces inward current, associated with the direct activation of nonselective cation channels by these metal ions. In excised inside-out membrane patches of neuroblastoma cells, micromolar concentrations of Ca activate small (SK) and big (BK) Ca-activated K channels. Internally applied Pb activates SK and BK channels more potently than Ca, whereas Cd is approximately equipotent to Pb with respect to SK channel activation, but fails to activate BK channels. The results show that metal ions cause distinct, selective effects on the various types of ion channels and that metal ion interaction sites of ion channels may be highly selective for particular metal ions.
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PMID:Metal interactions with voltage- and receptor-activated ion channels. 753 Nov 39

Aluminum is the most abundant metal and the third most common element in the earth's crust. It's toxicity has emerged as one of the most serious complications in the treatment of chronic renal failure. Aluminum lactate [Al(lac)3], at concentrations less than those affecting cell viability (< 5 mM) decreased the capability of mouse neuroblastoma cells to incorporate 14C-leucine and 3H-thymidine. This decreased capability to synthesize protein and DNA was accompanied by extension of neurites, increased capacity of the cells to take up silver stain, and decreased reactivity to antibodies against neurofilaments and to lectins that recognize cell surface carbohydrate residues. In conclusion, Allac3 should be considered as a marked cytostatic as well as a strong neuritogenic agent.
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PMID:Effects of aluminum lactate on murine neuroblastoma cells. 771 50

To study their cytotoxicity, clays containing aluminum silicates were added to cultures of primary murine spinal cord neurons and differentiated N1E-115 neuroblastoma cells. Bentonite (0.1 mg/ml) and montmorillonite (0.1 mg/ml) rapidly associated with the outer membrane of both N1E-115 and neuronal cells. Erionite (0.1 mg/ml) was randomly distributed throughout the culture. Both bentonite and montmorillonite caused complete cell lysis in the neuronal cultures within 60 min following addition. Erionite had no effect. None of the clays appeared to be cytotoxic to the differentiated N1E-115 cells even though bentonite and montmorillonite were closely associated with the cell membrane. N1E-115 cell lysis did not occur up to 18 h after addition of the clay. Aluminum silicate-containing clays caused a rapid lysis of primary neuronal cells. Differentiated N1E-115 neuroblastoma cells were not susceptible to clay-induced lysis, suggesting that the lytic mechanism is not a general phenomenon that affects all cell types equally.
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PMID:Cytotoxicity of aluminum silicates in primary neuronal cultures. 811 51

Concerning molecular and cellular mechanisms of aluminum toxicity, recent studies support the hypothesis that interactions of aluminum ions with elements of signal transduction pathways are apparently primary events in cells. In the case of the phosphoinositide-associated signalling pathway of neuroblastoma cells, guanine nucleotide-binding proteins (G proteins) and a phosphatidylinositol-4,5-diphosphate (PIP2)-specific phospholipase C are probable interaction sites for inhibitory actions of aluminum ions. Following interiorization of aluminum by the cell, metal interactions decrease the accumulation of inositol phosphates, especially that of inositol-1,4,5-triphosphate (IP3), concomitant with derangements of intracellular Ca2+ homeostasis. In the presence of high concentrations of Ca2+, formation of IP3 is also diminished in aluminum-pretreated cells, presumably involving a process not requiring Mg(2+)-dependent G proteins. At higher aluminum doses, metal-induced changes in the lipid milieu of the membrane-bound phospholipase may play a role. These types of primary interactions of aluminum ions with elements of cellular communication channels are probably crucial in the manifestation of the multifacetted aluminum toxicity syndrome. If present as a phosphate-like fluoro-aluminate, a stimulatory role of aluminum ions is displayed in G protein-coupled transmembrane signalling.
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PMID:Aluminum interaction with phosphoinositide-associated signal transduction. 816

The effects of the thyroid hormone triiodothyronine (T3), nerve growth factor (NGF) and stress (exposure to heat or aluminum sulfate) on growth, development and ageing of human neuroblastoma cells were studied in vitro. Differentiation of cells using retinoic acid and NGF inhibits cell growth and proliferation; simultaneously, it promotes acquisition of neuronal phenotype, down-regulation of T3 receptors, and an increase in catecholaminergic tyrosine hydroxylase activity and microtubule assembly. The actions of T3 on neuronal differentiation resemble those of NGF and suggest the existence of NGF-T3 interactions. Exposure to stress inhibits cell growth and proliferation, increases immunoreactivity to the microtubule-assembling protein tau (which occurs in paired filaments of neurofibrillary tangles in the aged human brain), and facilitates formation of tau-ubiquitin complexes (which also occur in the aged brain). Stress does not prevent the inhibition of cell proliferation by high doses of T3; however, T3 doses that are equivalent to physiological levels reduce stress-induced inhibition of growth. Previous studies have shown that stress may also induce in these cells facsimile lesions of normal and abnormal ageing, such as accumulation of lipofuscin pigments, formation of paired helical filaments and increased immunoreactivity to tau, beta-amyloid proteins, and ubiquitin. These lesions may represent cellular and molecular manifestations of increased vulnerability and susceptibility to genetic and extrinsic factors (e.g. hormones and environmental influences) with ageing. It is proposed that neuroblastoma cells may serve as a model to study mechanisms of neuronal ageing and to identify agents and conditions capable of preventing, delaying or reducing metabolic abnormalities leading to age-associated disorders.
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PMID:Alterations in the growth and protein content of human neuroblastoma cells in vitro induced by thyroid hormones, stress and ageing. 839 Oct 82

To assess the cytotoxicity of four clays containing an aluminum silicate--montmorillonite, bentonite, kaolinite and erionite--we used human umbilical vein endothelial, N1E-115 neuroblastoma, and ROC-1 oligodendroglial cells. Morphological examination, lactate dehydrogenase release and fatty acid release were used as indices of trauma. The clays were added in suspension to the cell cultures at concentrations of 0.1, 0.03 and 0.01 mg/ml of medium and the cells were incubated for 1, 6 and 24 h. The clays did not lyse ROC-1 and N1E-115 cells and did not cause a dose-dependent increase in fatty acid levels at 24 h. There were no significant increases in lactate dehydrogenase activity in N1E-115 neuroblastoma or ROC-1 oligodendroglial cells. In human umbilical vein endothelial cells, montmorillonite, kaolinite and bentonite caused a dose-dependent increase in fatty acids at 24 h. All three clays caused cell lysis. We postulate that the cytotoxicity of the clays containing an aluminum silicate towards endothelial cells may disrupt the blood-brain barrier in the affected areas, allowing the entry of the clay particle into the brain. Aluminum silicate clays caused a dose-dependent release of fatty acids in human umbilical vein endothelial cells. The clays also caused lysis of these cells. ROC-1 oligodendroglia and N1E-115 neuroblastoma cells were not lysed by the clays, suggesting that this is not a general phenomenon.
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PMID:Aluminum silicate toxicity in cell cultures. 839 48

Addition of 400 microM AlCl3 to the culture medium for 72 h has been previously shown to induce perikaryal whorls of intermediate-sized filaments in intact mouse NB2a/d1 neuroblastoma cells. Immunoblot analyses demonstrated that in vivo treatment of cells with aluminum induced the de novo appearance of extensively phosphorylated NF-H isoforms in cytoskeletons of undifferentiated cells and increased levels of these isoforms in differentiated cells. Neurofilament subunits isolated from intact cells treated with aluminum were resistant to dephosphorylation in vitro by alkaline phosphatase and to in vitro degradation by endogenous calcium-dependent protease(s). These alterations were accompanied by a greater tendency of neurofilaments to form insoluble aggregates after isolation. These findings demonstrate direct effects of aluminum on neurofilament subunits within intact neuronal cells similar to those previously demonstrated following in vitro exposure of isolated neurofilaments to aluminum.
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PMID:Aluminum treatment of intact neuroblastoma cells alters neurofilament subunit phosphorylation, solubility, and proteolysis. 858 20

Aluminum is known as a neurotoxic metal ion in experimental animals as well as in humans. The present study was carried out to determine whether and how the physicochemical properties of the metal coordination sphere (metal speciation) can influence the differentiation of murine neuroblastoma cells as has been observed previously in this laboratory (1). Results herein reported indicate that while the aluminum lipophilic species--particularly aluminum acetylacetonate (Alacac3) and aluminum maltolate (Almalt3), both hydrolitically stable and differently lipophilic--are both rather cytotoxic, metal hydrophilic species show different neuritogenic properties indicating the ability of Al(III), when diversely coordinated, to produce different biological effects.
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PMID:Aluminum speciation and morphological differentiation in murine neuroblastoma cells. 883 83

The effects of several metals on the serotonin receptor-channel complex were studied using mouse neuroblastoma N1E-115 cells which are known to be endowed with the 5-HT3 subclass of the receptor. The whole-cell patch clamp technique was used to record currents induced by serotonin at a concentration of 3 microM which was equivalent to the apparent dissociation constant. Methylmercury and mercuric chloride suppressed serotonin-induced currents irreversibly, with a 50% suppression being observed at concentrations of 3 microM and 2 microM, respectively. Lead and zinc suppressed the current with IC50S of 80 microM and 50 microM, respectively, and the effects of both metals were reversible after washing with metal-free solution. Lanthanum also suppressed the current with an IC50 of 10 microM, and the effect was partially reversible. Cadmium and cobalt augmented serotonin-induced currents slightly but consistently at a concentration of 100 microM, and the effect was reversible. Aluminum at 100 microM, had no effect on serotonin-induced currents. It was concluded that the 5-HT3 receptor is endowed with a unique property with respect to the actions of metals which is not shared by some other ligand-gated and voltage-gated ion channels.
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PMID:Modulation of serotonin-induced currents by metals in mouse neuroblastoma cells. 887 Sep 59


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