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)

In the end-stage renal disease patient, certain uremic compounds could influence the cellular accumulation of aluminum (Al). In this study, we examined the effect of 15 uremic ultrafiltrate fractions obtained by HPLC on the uptake and toxicity of Al in mouse hepatocytes (MH) in culture, a model system in which Al is taken up bound to transferrin (Tf). Uremic fractions 4 to 8, 12, 14, and 15 increased cellular Al uptake and aspartate aminotransferase release and decreased cell growth when Tf-Al, not Al citrate, was added to culture media. Compounds that have been extracted previously from these ultrafiltrate fractions (p-cresol, xanthine, tryptophan, hippuric acid, and o-hydroxyhippuric acid) were then tested for their effect on Al uptake and toxicity in MH at concentrations found in uremic serum. Significant Al uptake by MH was observed only when p-cresol was added together with Tf-Al. Time-response curves showed increased Al uptake and toxicity at p-cresol concentrations of 3 mg/dl in culture media. Dose-response curves confirmed that Al uptake and cell toxicity were proportional to p-cresol from 1.5 mg/dl to 3 mg/dl in culture media. p-Cresol was not toxic to MH in the absence of Tf-Al in media. p-Cresol increased Tf-associated Al uptake only because there was no effect on Al uptake when Al citrate was substituted, and studies with Tf-I125-Al in the presence of this compound showed increased Tf-I125 taken up by MH. p-Cresol did not increase Tf saturation with Al. p-Cresol also increased Tf-Al uptake in Friend erythroleukemia and neuroblastoma cells in culture. Our studies suggest that p-cresol and uremic fractions 4 to 8, 12, 14, and 15 increase the uptake and toxicity of Al in cultured MH. These compounds may play a role in the accumulation and toxicity of Al in the liver of end-stage renal disease patients and possibly in all cells that express Tf receptors.
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PMID:P-Cresol, a uremic compound, enhances the uptake of aluminum in hepatocytes. 918 61

We have studied the uptake and removal of gallium, used as an analogue of aluminum, and the effects of aluminum itself on cultured human neuroblastoma cells treated with soluble metal complexes. The prohibitively high cost of measurement of the only available radioisotope of aluminum (26Al) precluded its usage, and so we considered that gallium, which is chemically extremely similar, would be the most suitable model. Gallium has been used thus in a number of previous biological studies and has been found to behave like aluminum in many respects. We have previously shown that Al-EDTA treatment results in uptake of aluminum and expression of hyperphosphorylated tau, a key component of Alzheimer's disease paired helical filaments. Here we demonstrate that gallium uptake can occur by two separate methods, both leading to physiologically relevant intracellular metal concentrations. Uptake from medium containing bovine transferrin occurred mainly by pinocytosis, but in the presence of human transferrin (hTf), uptake by transferrin-mediated endocytosis occurred also, despite a very low level of hTf saturation, indicating that Tf-mediated uptake is a very effective method of Ga internalization. The intracellular gallium is relatively stable, though partially removable by (1 mM) EDTA, desferrioxamine, or 1,2-dimethyl-3-hydroxypyrid-4-one. Aluminum and gallium treatment were found to increase the overall activity of lysosomal proteases, enzymes implicated in amyloid precursor protein cleavage. No effects were detected on choline acetyl transferase activity, cell growth, or tritiated thymidine incorporation or on the structure of the cells, as judged by light or electron microscopy.
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PMID:Mechanisms of uptake of gallium by human neuroblastoma cells and effects of gallium and aluminum on cell growth, lysosomal protease, and choline acetyl transferase activity. 978 93

Aluminum (Al) and iron (Fe) have been implicated as playing a toxic role in the pathologic lesions of Alzheimer's disease. In the following report we describe the uptake and toxicity of Al, the effect of Al on Fe uptake, and the expression of neurofibrillary tangle (NFT) protein in murine neuroblastoma cells (Neuro 2A). Significant cell Al uptake and inhibition of cell growth were seen in Neuro 2A cells at 24, 48, 72, and 96 h after plating in medium containing Al transferrin (Al-Tf) and Al citrate. Al-loaded Neuro 2A cells showed increased rates of 59Fe and 125I-Tf uptake and total cellular Fe content at 24, 48, 72, and 96 h after plating compared with control cultures. Significant increases in NFT protein staining were detected in Al-exposed cells at 72 and 96 h in culture compared with controls. The intensity of NFT staining in Al-loaded cells was directly proportional to the time in culture. There was no difference in malonyldialdehyde levels measured in control versus Al-loaded Neuro 2A cells. These results suggest that the accumulation of Al in Neuro 2A cells resulted in increased uptake of Fe, inhibition of cell growth, and expression of NFT protein, partially mimicking the pathological hallmarks of Alzheimer's disease. This model system may also be applicable for Al-induced dialysis dementia, because the Al concentrations at which cell toxicity occurred can be found in dialysis patients.
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PMID:Aluminum enhances iron uptake and expression of neurofibrillary tangle protein in neuroblastoma cells. 1021 85

Aluminum, a trivalent cation unable to undergo redox reactions, has been linked to many diseases such as dialysis dementia and microcytic anemia without iron deficiency. It has also been implicated in Alzheimer's disease although this is controversial. Because cell death due to oxidative injury is suspected to be a contributory factor in many neurological diseases and aluminum neurotoxicity, glioma (C-6) and neuroblastoma (NBP2) cells were utilized to assess early changes in oxidative parameters consequent to a 48-h exposure to aluminum sulfate. A 500-microM concentration of this salt produced a significant increase in reactive oxygen species (ROS) production and a significant decrease in glutathione (GSH) content in glioma cells. However, the same concentration of the aluminum salt did not lead to any significant changes in the neuroblastoma cells. Mitochondrial respiratory activity in glioma cells was also found to be significantly higher in the aluminum treated cells. As judged by morin-metal complex formation, aluminum can enter glioma cells much more readily than neuroblastoma cells. Thus, it is possible that the cerebral target following an acute exposure to aluminum may be glial rather than neuronal.
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PMID:Aluminum-induced oxidative events in cell lines: glioma are more responsive than neuroblastoma. 1038 Nov 87

Several epidemiological studies suggest the involvement of aluminum (Al) in the pathogenesis of Alzheimer's disease (AD). There is an increase in the levels of Abeta and ubiquitin in the pathological lesions of AD. Therefore, we have investigated whether aluminum (Al) treatment alters the levels of Abeta and ubiquitin in murine neuroblastoma (NBP2) and rat glioma (C-6) cell cultures. At a low concentration (10 microM), aluminum sulfate stimulated the level of immunoreactive Abeta and ubiquitin in NBP2 cells without changing the levels of the amyloid precursor protein (APP). However, at higher concentrations (100 and 500 microM), aluminum failed to elicit any significant effect on beta-amyloid, whereas ubiquitin levels continued to increase. No changes in the Abeta and ubiquitin content were found in the C-6 glioma cells following treatment with Al at any of the concentrations tested. Exposure of cells to aluminum salts did not alter the rate of proliferation in either of the two cell lines. These data suggest that one of the mechanisms by which Al may play a role in AD is by promoting the formation of Abeta and ubiquitin in neurons.
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PMID:Aluminum increases levels of beta-amyloid and ubiquitin in neuroblastoma but not in glioma cells. 1072 Oct 10

We evaluated the levels of aluminium in a total of 72 samples of 17 different spices and aromatic herbs that are widely consumed in Spain, and in the Mediterranean diet, in general. Aluminium was determined in the samples mineralized with HNO3 and V2O5, using electrothermal atomization atomic absorption spectroscopy as the analytical technique. The accuracy and precision of the proposed method was verified against an NBS-certified reference material. Precision, expressed as relative standard deviation, ranged from 1.10 to 4.07%. The results obtained from recovery studies were of 97.90 +/- 1.20. Aluminium concentrations ranged from 3.74 to 56.50 microg/g (dry wt.). The presence of this metal was detected in all the samples we analysed.
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PMID:Aluminium levels in spices and aromatic herbs. 1098 28

Aluminum is highly oxophilic and its minerals are usually found surrounded by six oxygen atoms. A role for the metal has been established in dialysis encephalopathy and Al-induced osteomalacia. The metal has been implicated in Alzheimer's disease but the issue is at present controversial. Human cell lines of neural origin were utilized to study the effect of lipophilic aluminum acetylacetonate and non-lipophilic aluminum sulfate on cell proliferation and viability. Although analysis of Al species in the cell culture media demonstrated that there are positively charged Al species present in solutions prepared with both Al salts, only the aluminum acetylacetonate salt caused changes in cell proliferation and viability. Therefore, the lipophilic nature of the organic Al salt is a critical determinant of toxicity. The effect of aluminum acetylacetonate was dose-dependent and time-dependent. Neuroblastoma (SK-N-SH) cells were more susceptible to decreased cell proliferation although the lipophilic Al salt was more toxic to the glioblastoma (T98G) cells. While the toxicity of aluminum acetylacetonate was inhibited in the T98G cells by the addition of phosphate, the same treatment did not reverse cell death in the SK-N-SH cells. Thus, the mechanism of Al toxicity appears to be different in the two cell lines. It is possible that the principal neurotoxic target of the metal is glial and when these cells are in a compromised state, this may secondarily impact the neuronal population and thus eventually lead to neurodegeneration.
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PMID:Differential toxicity of aluminum salts in human cell lines of neural origin: implications for neurodegeneration. 1130 52

Our approach to examine the mechanism(s) of action for photodynamic therapy (PDT) has been via the generation of PDT-resistant cell lines. In this study we used three human cell lines, namely, human colon adenocarcinoma (HT29), human bladder carcinoma and human neuroblastoma. The three photosensitizers used were Photofrin, Nile Blue A and aluminum phthalocyanine tetrasulfonate. The protocol for inducing resistance consisted of repeated in vitro photodynamic treatments with a photosensitizer to the 1-10%-survival level followed by regrowth of single surviving colonies. Varying degrees of resistance were observed. The three induced variants of the HT29 cell line were the most extensively studied. Their ratios of increased survival at the LD90 level range between 1.5- and 2.62-fold more resistant.
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PMID:In vitro induction of PDT resistance in HT29, HT1376 and SK-N-MC cells by various photosensitizers. 1142 Oct 71

The effects of aluminum(III) on microtubular meshwork have been investigated using cultured murine neuroblastoma cells grown in a medium containing aluminum lactate at defined metal concentrations (10-20 microM). A role of aluminum(III) in promoting neuronal plasticity events is suggested. These events including sprouting and neurite outgrowth are associated with an increased tyrosine-tubulin (Tyr-Tub) expression, which can be due to the enhanced needs of recently formed, highly dynamic microtubules typical of neuronal plasticity. After 48 and 72 h aluminum exposure, an upregulation of Tyr-Tub expression is detected and this is concentration-dependent. A high amount of Tyr-Tub is observed also in non-treated cells, although later than in aluminum-exposed cells. Thus, it is possible that aluminum(III) accelerates neuronal plasticity events, for which Tyr-Tub is confirmed to be a useful marker.
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PMID:Aluminum promotes neuronal plasticity events in a mouse neuroblastoma cell line. 1157 32

Aluminum effects on cultured human brain cells were examined. Human brain cells (neuroblastoma IMR-32) were cultured to examine possible effects of soluble aluminum at a cellular level. The cellular growth rate was measured by counting the number of cells with a hemocytometer under an optical microscope over a period of time. No significant change in cell growth was found during a three-week exposure period to aluminum at concentrations from 0.1 to 10 mg/l. However, after 3 weeks Al started to reduce the growth rate relative to the control, and the decrease became more pronounced as the exposure period to aluminum increased. The effect was greatest at the higher Al-concentration.
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PMID:Aluminum exposure: a study of an effect on cellular growth rate. 1166 61


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