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 conditions (e.g. pH, resin, particle size, foreign ions) affecting the uptake of Cd(II), Cr(III), Cu(II) and Pb(II) from aqueous solution by the SM-7 (also called XAD-7) resin, were studied. Based on these studies, a two-column method was developed to overcome the effect of complexation by humic substances. The method was successfully tested with the NBS multielement water standard, SRM 1643a, and was subsequently applied to enrich Cd(II), Cr(III), Cu(II) and Pb(II) in 15 drinking water samples from Hamilton, Ontario. The metals were determined using graphite furnace atomic absorption spectrometry. The results for the drinking water samples showed that leaching of copper and lead occurred from the distribution system.
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PMID:Preconcentration of cadmium, chromium, copper and lead in drinking water on the polyacrylic ester resin, XAD-7. 400 60

The validity of 2 electrothermal atomic absorption spectrometric methods for determination of selenium in foods and diets was tested. By using 0.5% Ni(II) as a matrix modifier to prevent selenium losses during the ashing step, it was shown that selenium can be determined in samples containing greater than or equal to 1 microgram Se/g dry wt without organic extraction. The mean recovery tested, using NBS Bovine Liver, was 98%; recovery of added inorganic selenium in Bovine Liver matrix was 100%. In addition, this method gave values closest to the median value of all participating laboratories using hydride generation AAS or the spectrofluorometric method in a collaborative study on high selenium wheat, flour, and toast samples. For samples with concentrations less than 1 microgram Se/g dry wt, separation of selenium from interfering Fe and P ions by organic extraction was necessary. Using inorganic 75Se in meat and human milk matrixes, an ammonium pyrrolidine dithiocarbamate-methyl isobutyl ketone-extraction system with added Cu(II) as a matrix modifier yielded the best extraction recoveries, 97 and 98%, respectively. Accuracy and precision of the method were tested using several official and unofficial biological standard materials. The mean accuracy was within 4% of the certified or best values of the standard materials and the day-to-day variation was 9%. The Se/Fe or Se/P interference limits proved to be low enough not to affect selenium determinations in practically all foods or diets. The practical detection limit of the method was 3 ng Se/g dry wt for 1.0 g dry wt samples.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrothermal atomic absorption spectrometric determination of selenium in foods and diets. 663 Jan 25

Processing of the recycling proteoglycan glypican-1 involves the release of its heparan sulfate chains by copper ion- and nitric oxide-catalyzed ascorbate-triggered autodegradation. The Alzheimer disease amyloid precursor protein (APP) and its paralogue, the amyloid precursor-like protein 2 (APLP2), contain copper ion-, zinc ion-, and heparan sulfate-binding domains. We have investigated the possibility that APP and APLP2 regulate glypican-1 processing during endocytosis and recycling. By using cell-free biochemical experiments, confocal laser immunofluorescence microscopy, and flow cytometry of tissues and cells from wild-type and knock-out mice, we find that (a) APP and glypican-1 colocalize in perinuclear compartments of neuroblastoma cells, (b) ascorbate-triggered nitric oxidecatalyzed glypican-1 autodegradation is zinc ion-dependent in the same cells, (c) in cell-free experiments, APP but not APLP2 stimulates glypican-1 autodegradation in the presence of both Cu(II) and Zn(II) ions, whereas the Cu(I) form of APP and the Cu(II) and Cu(I) forms of APLP2 inhibit autodegradation, (d) in primary cortical neurons from APP or APLP2 knock-out mice, there is an increased nitric oxide-catalyzed degradation of heparan sulfate compared with brain tissue and neurons from wild-type mice, and (e) in growth-quiescent fibroblasts from APLP2 knock-out mice, but not from APP knock-out mice, there is also an increased heparan sulfate degradation. We propose that the rate of autoprocessing of glypican-1 is modulated by APP and APLP2 in neurons and by APLP2 in fibroblasts. These observation identify a functional relationship between the heparan sulfate and copper ion binding activities of APP/APLP2 in their modulation of the nitroxyl anion-catalyzed heparan sulfate degradation in glypican-1.
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PMID:The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo. 1567 59

Dopaminergic human neuroblastoma SH-SY5Y cells were stably transformed to increase expression of alpha-synuclein, a Parkinson's disease-related protein. Transformed cells were more resistant to oxidative insults, showing a cytoprotective role of alpha-synuclein. The expression of redox chaperonins (DJ-1, HSP70, and 14-3-3) was evaluated by Western blotting. Expression of alpha-synuclein reduced HSP70 levels even in the presence of dopamine, with a twofold increase of DJ-1 in the absence of oxidants. DJ-1 is significantly reduced by dopamine, and even more by dopamine and Cu(II). Increased alpha-synuclein expression did not affect 14-3-3, although dopamine increased its level by 60% in wild-type cells. alpha-Synuclein not only upregulated DJ-1, but also shifted all DJ-1 forms to a single spot at pI=5.7 not observed in wild-type cells. Dopamine gradually restored the distribution of DJ-1 forms to a situation similar to wild-type cells, with the form at pI=6.1 progressively enriched under oxidative conditions.
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PMID:alpha-Synuclein protects SH-SY5Y cells from dopamine toxicity. 1697 83

Co-Administration of Cu(II) chelates are reported to decrease life threatening Cisplatin [Pt(II) (NH3)2(CL)2]-induced acute degenerative renal, gastrointestinal, thymic, and bone marrow states consistent with serious necrotizing and immune-mediated inflammatory disease. Initially it was found that copper sulfate treatment completely prevented lethality as well as gastric and nephrotoxicity without compromising Pt(II) (NH3)2(CL) 2 antineoplastic activity, which led to suggestions that prior Cu(II)-treatment be used clinically to prevent serious side effects of Pt(II) (NH3)2(CL)2-treatment. In the course of these studies it was discovered that Cu(II)-treatments alone inhibited neoplastic growth and increased survival of rat and mouse models of cancer. Subsequently it was discovered that a stable non-toxic and non-polar lipophilic chelate, Copper(II)2(3,5-diisopropylsalicylate)4, caused redifferentiation of cultured neuroblastoma and mouse muscle-implanted mammary adenocarcinoma without neoplastic cell killing. Another stable non-toxic and non-polar lipophilic chelate, Copper(II)2(3,5-ditertiarybutylsalicylate)4, was found to prevent Bax-initiated and caspases-3-activation mediated apoptosis. These remarkable observations are concluded to be due to enzyme-mimetic or modulating reactivities of Cu(II) chelates and/or facilitation of Cu(II or I)-dependent enzyme syntheses required to overcome inflammatory-neoplastic disease states. Further, approaches to treating neoplastic diseases by removal of Cu from tissues with ammonium tetrathiomolybdate in an anticopper approach to therapy are not well founded based upon existing scientific literature.
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PMID:Co-treatment with copper compounds dramatically decreases toxicities observed with cisplatin cancer therapy and the anticancer efficacy of some copper chelates supports the conclusion that copper chelate therapy may be markedly more effective and less toxic than cisplatin therapy. 1758 59

A series of mononuclear complexes with Co(II), Ni(II), Cu(II), Zn(II), Hg(II), Mo(VI) and Pd(II) containing the ligand derived from the 1:2 condensation of 2,6-diformyl-4-methylphenol and 5,6-diamino-1,3-dimethyluracil (hereafter denoted as BDFDAAU) were synthesized. The complexes were characterized by elemental analysis, thermogravimetry (TG) and differential scanning calorimetry (DSC), IR, (1)H, (13)C and (15)N NMR, UV-visible-near IR (UV-VIS-NIR), EPR and magnetic measurements. The deprotonated ligand in the phenolic oxygen shows a symmetric tridentate coordination mode through the two azomethine nitrogen atoms and the phenolic oxygen atom whereas the coordination of the neutral ligand takes place through the phenolic oxygen atom and one azomethine nitrogen atom. In the Mo(VI) complex, the ligand is bideprotonated in the phenolic oxygen and an amino group from one uracil unit; so, the coordination mode changes again into an asymmetric way: phenolic oxygen atom, one azomethine nitrogen atom and the nitrogen atom from the deprotonated amino group. The antiproliferative behaviour against the five human tumor cell lines (human neuroblastoma NB69, human breast cancer MCF-7 and EVSA-T, human glioma H4 and human bladder carcinoma cell line ECV) suggested a modulator behaviour, according to the concentration, of cell growth due to their estrogen-like characteristics.
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PMID:Synthesis, characterization and antiproliferative activity of metal complexes with the Schiff base derived from the condensation 1:2 of 2,6-diformyl-4-methylphenol and 5,6-diamino-1,3-dimethyluracil. 1803 89

This review provides an overview of the synthesis and metal complexation chemistry of the nitrogen and sulphur donor bicyclic ligands or cages, and the key criteria that led to the design of sarar for the application for (64)Cu(II). Aspects of the high yielding synthesis of sarar and strategies for its conjugation to a range of antibodies for targeting colorectal cancer, neuroblastoma and melanoma are described. Free and conjugated to proteins sarar can complex (64)Cu(II) rapidly at room temperature and quantitatively; the latter leading to products of high specific activity and purity. The full occupation of the (64)Cu(II) ions 6 coordination sites by the sarar cage prevents the ready exchange of the (64)Cu(II) from the cage and is the rational for the extraordinary thermodynamic and kinetic stability of (64)Cu(II) labelled sarar and its conjugates. It's in vivo stability is further highlighted by the low uptake and retention of (64)Cu-sarar-conjugated antibodies in the liver. Finally, the prospects for the use of the sarar technology in the materials science arena for probing solid liquid interfaces, in particular, the quantification of functional groups on microspheres and in the engineering of novel materials are discussed.
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PMID:Sarar technology for the application of Copper-64 in biology and materials science. 1817 77

6-Hydroxydopamine (6-OHDA) is a neurotoxin to produce an animal model of Parkinson's disease. 6-OHDA increased the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG), a biomarker of oxidatively damaged DNA, and induced apoptosis in human neuroblastoma SH-SY5Y cells. Iron or copper chelators inhibited 6-OHDA-induced 8-oxodG formation and apoptosis. Thus, iron and copper are involved in the intracellular oxidatively generated damage to DNA, a stimulus for initiating apoptosis. This study examined DNA damage caused by 6-OHDA plus metal ions using (32)P-5'-end-labelled DNA fragments. 6-OHDA increased levels of oxidatively damaged DNA in the presence of Fe(III)EDTA or Cu(II). Cu(II)-mediated DNA damage was stronger than Fe(III)-mediated DNA damage. The spectrophotometric detection of p-quinone and the scopoletin method showed that Cu(II) more effectively accelerated the 6-OHDA auto-oxidation and H(2)O(2) generation than Fe(III)EDTA. This study suggests that copper, as well as iron, may play an important role in 6-OHDA-induced neuronal cell death.
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PMID:Mechanism of metal-mediated DNA damage and apoptosis induced by 6-hydroxydopamine in neuroblastoma SH-SY5Y cells. 1865 80

Tetrahydroisoquinoline (TIQ) derivatives are putative neurotoxins that may contribute to the degeneration of dopaminergic neurons in Parkinson's disease. One TIQ, norsalsolinol (NorSAL), is present in dopamine-rich areas of human brain, including the substantia nigra. Here, we demonstrate that NorSAL reduces cell viability and induces apoptosis via cytochrome c release and caspase 3 activation in SH-SY5Y human neuroblastoma cells. Cytochrome c release, caspase 3 activation, and apoptosis induction were all inhibited by the antioxidant N-acetylcysteine. Thus, reactive oxygen species (ROS) contribute to apoptosis induced by NorSAL. Treatment with NorSAL also increased levels of oxidative damage to DNA, a stimulus for apoptosis, in SH-SY5Y. To clarify the mechanism of intracellular DNA damage, we examined the DNA damage caused by NorSAL using (32)P-5'-end-labeled isolated DNA fragments. NorSAL induced DNA damage in the presence of Cu(II). Catalase and bathocuproine, a Cu(I) chelator, inhibited this DNA damage, suggesting that ROS such as the Cu(I)-hydroperoxo complex derived from the reaction of H(2)O(2) with Cu(I), promote DNA damage by NorSAL. In summary, NorSAL-generated ROS induced oxidative DNA damage, which led to caspase-dependent apoptosis in neuronal cells.
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PMID:The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson's disease. 1901 44

Amyloid-beta peptides (Abeta) and the protein human serum albumin (HSA) interact in vivo. They are both localised in the blood plasma and in the cerebrospinal fluid. Among other functions, HSA is involved in the transport of the essential metal copper. Complexes between Abeta and copper ions have been proposed to be an aberrant interaction implicated in the development of Alzheimer's disease, where Cu is involved in Abeta aggregation and production of reactive oxygen species (ROS). In the present work, we studied copper-exchange reaction between Abeta and HSA or the tetrapeptide DAHK (N-terminal Cu-binding domain of HSA) and the consequence of this exchange on Abeta-induced ROS production and cell toxicity. The following results were obtained: 1) HSA and DAHK removed Cu(II) from Abeta rapidly and stoichiometrically, 2) HSA and DAHK were able to decrease Cu-induced aggregation of Abeta, 3) HSA and DAHK suppressed the catalytic HO(.) production in vitro and ROS production in neuroblastoma cells generated by Cu-Abeta and ascorbate, 4) HSA and DAHK were able to rescue these cells from the toxicity of Cu-Abeta with ascorbate, 5) DAHK was more potent in ROS suppression and restoration of neuroblastoma cell viability than HSA, in correlation with an easier reduction of Cu(II)-HSA than Cu-DAHK by ascorbate, in vitro. Our data suggest that HSA is able to decrease aberrant Cu(II)-Abeta interaction. The repercussion of the competition between HSA and Abeta to bind Cu in the blood and brain and its relation to Alzheimer's disease are discussed.
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PMID:Copper transfer from Cu-Abeta to human serum albumin inhibits aggregation, radical production and reduces Abeta toxicity. 1993 95


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