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)

Defective copper excretion in Wilson's disease can result in increased neurological copper concentrations. This is thought to occur following exposure to increased circulating copper released from necrotic hepatocytes in a saturated liver. BU17 human glioma cells and SH-SY5Y human neuroblastoma cells were exposed to media supplemented with copper in the range 0-250 microM for periods up to 48 h to investigate this hypothesis. Copper uptake, cell growth, intracellular radical generation, and oxidative stress were measured in copper exposed cells. No increase in copper uptake or inhibition of cell growth could be measured in either cell type at any time point or copper concentration investigated. However, significant increases in radical generation (p < 0.001) could be measured in both BU17 and SH-SY5Y cells. A decreased ability to cope when the cells were exposed to additional pro-oxidants suggested that the cells were under oxidative stress with significant reductions in cell viability following exposure to both copper and ascorbic acid. These data suggest that copper sequestration does not occur in neuronal cells exposed to elevated extracellular copper concentrations.
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PMID:The response of neurones and glial cells to elevated copper. 1147 Mar 18

Treatment of SH-SY5Y human neuroblastoma cells with copper sulphate (50-300microM) in complete medium for 24h caused an increase in the level of the metal both in whole cells and in isolated mitoplasts. Toxic effects of copper resulted in the impairment of the capability of mitochondrial dehydrogenases to reduce a tetrazolium salt, and, to a lesser extent, in the loss of the integrity of the plasma membrane. The mechanism of toxicity involved the production of reactive oxygen species, amplified by the presence of ascorbate. Decreases in the levels of several mitochondrial proteins (subunits of complex I, complex V, and of the pyruvate dehydrogenase complex) were observed. These findings demonstrate that mitochondria are an early and susceptible target of copper-mediated oxidative stress in neuronal cells and support the hypothesis that mitochondrial damage triggers the neurodegenerative processes associated with copper overload in Wilson's disease.
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PMID:Copper-dependent toxicity in SH-SY5Y neuroblastoma cells involves mitochondrial damage. 1562 36

The basic mechanism(s) by which altered Cu homeostasis is toxic to hepatocytes and neurons, the two major cell types affected in copper storage diseases such as Wilson's disease (WD), remain unclear. Using human M17 neuroblastoma cells as a model to examine Cu toxicity, we found that there was a time- and concentration-dependent induction of neuronal death, such that at 24 h there was a approximately 50 % reduction in viability with 25 muM Cu-glycine(2). Cu-glycine(2) (25:50 muM) treatment for 24 h significantly altered the expression of 296 genes, including 8 genes involved with apoptosis (BCL2-associated athanogene 3, BCL2/adenovirus E1B 19kDa interacting protein caspase 5, regulator of Fas-induced apoptosis, V-jun sarcoma virus 17 oncogene homolog, claudin 5, prostaglandin E receptor 3 and protein tyrosine phosphatase, non-receptor type 6). Surprisingly, changes in the expression of more 'traditional' apoptotic genes (Bcl-2, Bax, Bak and Bad) did not vary more than 20 %. To test whether the induction of apoptosis in neuroblastoma cells was via post-translational mechanisms, we measured the protein expression of these apoptotic markers in M17 neuroblastoma cells treated with Cu-glycine(2) (0-100 muM) for 24-48 h. Compared with glycine treated cells, Cu-glycine(2) reduced Bcl-2 expression by 50 %, but increased Bax and Bak expression by 130% and 400 %, respectively. To assess whether Cu also induced apoptotic cell death in a mouse model of WD, we measured the expression of these apoptotic markers in the liver and brain of mice expressing an ATP7b gene mutation (tx(J) mice) at 10 months of age (near the end of their lives when overt liver pathology is displayed). Changes in the liver expression of these apoptotic markers in tx(J) mice compared to background mice mirrored those of Cu treated neuroblastoma cells. In contrast, few changes in apoptotic protein expression were detected in the brain between tx(J) and background mice, indicating the tx(J) mouse is a good model of hepatic, but not brain, Cu toxicity. Our results indicate that Cu-induction of neuronal apoptosis does not require de novo synthesis or degradation of apoptotic genes, and that Cu accumulation in the aged tx(J) mouse brain is insufficient to induce apoptosis.
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PMID:Copper Induces Apoptosis of Neuroblastoma Cells Via Post-translational Regulation of the Expression of Bcl-2-family Proteins and the tx Mouse is a Better Model of Hepatic than Brain Cu Toxicity. 1907 89