Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Alzheimer's disease there is abnormal brain copper distribution, with accumulation of copper in amyloid plaques and a deficiency of copper in neighbouring cells. Excess copper inhibits Abeta (amyloid beta-peptide) production, but the effects of deficiency have not yet been determined. We therefore studied the effects of modulating intracellular copper levels on the processing of APP (amyloid precursor protein) and the production of Abeta. Human fibroblasts genetically disposed to copper accumulation secreted higher levels of sAPP (soluble APP ectodomain)alpha into their medium, whereas fibroblasts genetically manipulated to be profoundly copper deficient secreted predominantly sAPPbeta and produced more amyloidogenic beta-cleaved APP C-termini (C99). The level of Abeta secreted from copper-deficient fibroblasts was however regulated and limited by alpha-secretase cleavage. APP can be processed by both alpha- and beta-secretase, as copper-deficient fibroblasts secreted sAPPbeta exclusively, but produced primarily alpha-cleaved APP C-terminal fragments (C83). Copper deficiency also markedly reduced the steady-state level of APP mRNA whereas the APP protein level remained constant, indicating that copper deficiency may accelerate APP translation. Copper deficiency in human neuroblastoma cells significantly increased the level of Abeta secretion, but did not affect the cleavage of APP. Therefore copper deficiency markedly alters APP metabolism and can elevate Abeta secretion by either influencing APP cleavage or by inhibiting its degradation, with the mechanism dependent on cell type. Overall our results suggest that correcting brain copper imbalance represents a relevant therapeutic target for Alzheimer's disease.
 ...
PMID:Intracellular copper deficiency increases amyloid-beta secretion by diverse mechanisms. 1824 25

Some oxindole-Schiff base copper(II) complexes have already shown potential antitumor activity towards different cells, inducing apoptosis in a process modulated by the ligand, and having nuclei and mitochondria as main targets. Here, three novel copper(II) complexes with analogous ligands were isolated and characterized by spectroscopic techniques, having their reactivity compared to the so far most active complex in this class. Cytotoxicity experiments carried out toward human neuroblastoma SH-SY5Y cells confirmed its pro-apoptosis property. DNA cleavage studies were then performed in the presence of these complexes, in order to verify the influence of ligand structural features in its nuclease activity. All of them were able to cause double-strand DNA scissions, giving rise to nicked circular Form II and linear Form III species, in the presence of hydrogen peroxide. Additionally, DNA Form II was also detected in the absence of peroxide when the most active complex, [Cu(isaepy)2]2+ 1, was used. In an effort to better elucidate their interactions with DNA, solutions of the different complexes titrated with DNA had their absorption spectra monitored. An absorbance hyperchromism observed at 260 nm pointed to the intercalation of these complexes into the DNA structure. Further, investigations of 2-deoxy-d-ribose (DR) oxidation catalyzed by each of those complexes, using 2-thiobarbituric acid reactive species (TBARS) method, and detection of reactive oxygen species (ROS) formation by spin-trapping EPR, suggested that their mechanism of action in performing efficiently DNA cleavage occurs preferentially, but not only by oxidative pathways.
 ...
PMID:Double-strand DNA cleavage induced by oxindole-Schiff base copper(II) complexes with potential antitumor activity. 1829 39

We have developed a general and efficient method for copper-catalyzed amidation of saturated C-H bonds under mild conditions, and the used substrates include benzylic reagents, the N, N-dimethylaniline derivatives, the free carboxamides, and sulfonamides. The protocol uses inexpensive and readily available CuBr/ N-halosuccinimide (NBS or NCS) as the catalyst/oxidant, so it provides practical applications for synthesis of various amides via C-H activation.
 ...
PMID:General and efficient copper-catalyzed amidation of saturated C-H bonds using N-halosuccinimides as the oxidants. 1859 84

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.
 ...
PMID:Mechanism of metal-mediated DNA damage and apoptosis induced by 6-hydroxydopamine in neuroblastoma SH-SY5Y cells. 1865 80

As reported by some authors, clioquinol (CQ), a 8-hydroxyquinoline derivative, has produced very encouraging results in the treatment of Alzheimer's disease (AD). Its biological effects are most likely ascribed to complexation of specific metal ions, such as copper (II) and zinc (II), critically associated with beta-amyloid (A beta) aggregation/fibrillogenesis and degeneration processes in the brain. The present study was aimed at assessing the in vitro effects of CQ on the aggregation/fibrillogenesis properties of human A beta either alone or complexed with Cu(2+) and Zn(2+). Surprisingly, our data indicated that CQ promoted rather than inhibited the formation of A beta fibrillar aggregates when added metal ions were present. To understand whether the latter effects were related to the peptide amino acid sequence, we also investigated the aggregational profile of rat A beta, which differs from the human homologous for three amino acidic substitutions. Such a sequence alteration drastically reduced the tendency of the peptide to undergo spontaneous aggregation/fibrillization. In the presence of CQ and metals, however, also rat A beta showed a strong propensity to generate fibrillar aggregates. In agreement with the pro-aggregation effects observed in solution, studies with neuroblastoma cells demonstrated an impairment of cell functioning only in the presence of CQ + A beta-metals. Based on the present findings, the literature data on the potential effectiveness of CQ-based chelation therapy in AD should be re-interpreted.
 ...
PMID:Mutual stimulation of beta-amyloid fibrillogenesis by clioquinol and divalent metals. 1871 94

The cellular prion protein (PrP(c)) plays a crucial role in the pathogenesis of prion diseases, but its physiological function is far from understood. Several candidate functions have been proposed including binding and internalization of metal ions, a superoxide dismutase-like activity, regulation of cellular antioxidant activities, and signal transduction. The transmembrane (TM1) region of PrP(c) (residues 110-135) is particularly interesting because of its very high evolutionary conservation. We investigated a possible role of TM1 in the antioxidant defense, by assessing the impact of overexpressing wt-PrP or deletion mutants in N(2)A mouse neuroblastoma cells on intracellular reactive oxygen species (ROS) levels. Under conditions of oxidative stress, intracellular ROS levels were significantly lowered in cells overexpressing either wild-type PrP(c) (wt-PrP) or a deletion mutant affecting TM1 (Delta8TM1-PrP), but, as expected, not in cultures overexpressing a deletion mutant lacking the octapeptide region (Deltaocta-PrP). Overexpression of wt-PrP, Delta8TM1-PrP, or Deltaocta-PrP did not affect basal ROS levels. Interestingly, the mitochondrial membrane potential was significantly lowered in Deltaocta-PrP-transfected cultures in the absence of oxidative stress. We conclude that the protective effect of PrP(c) against oxidative stress involves the octarepeat region but not the TM1 domain nor the high-affinity copper binding site described for human residues His96/His111.
 ...
PMID:The octarepeat region of prion protein, but not the TM1 domain, is important for the antioxidant effect of prion protein. 1882 94

In aqueous ethanol cobalt(II), nickel(II) and copper(I) react instantaneously with 2,3-quinoxalinedithiol at pH 2 to form strongly coloured complexes exhibiting absorption maxima at 510, 606 and 665, and 625 nm, respectively. At pH 6 the reaction of copper can be virtually eliminated, while the cobalt and nickel reactions show only small decreases in sensitivity. This behaviour has been made the basis of a rapid method for the simultaneous determination of these three elements. The absorbances of the complexes have been found to be additive for all combinations of these elements in which the individual concentrations have been varied from approximately 0.1 to 1 ppm. A least-squares estimate of the concentration of any of the elements may be readily obtained by using a simple linear equation based on the absorbance readings and a set of constants derived from the spectrophotometric data. The analyses of seven synthetic solutions and four NBS Standard Reference Materials yielded a maximum error of 6.0% and an average error of 1.6%.
 ...
PMID:Simultaneous spectrophotometric determination of cobalt, nickel and copper with 2,3-quinoxaline- dithiol. 1896 Jul 30

A continuously operating hydride-generation system has been developed for determination of volatile hydride-forming elements such as arsenic and selenium by d.c. plasma atomic-emission spectrometry. Arsenic and selenium are converted into their hydrides by reduction with sodium borohydride. The hydrides evolved are stripped from the liquid phase in a gas/liquid separator and are continuously fed into the d.c. plasma by a small argon stream. Under optimized operating conditions the detection limits (3s) obtained for arsenic and selenium are 0.3 and 0.5, mug/l., respectively. The precision at the 5 mu/l. level is better than 4% r.s.d. The measurement time, including sample introduction and three replicate measurements with 5-sec integration per sample is about 1 min. The effects of well known interferents such as copper and nickel have been investigated. For minimizing their interference continuous addition of 1, 10-phenanthroline as masking agent has been found useful. The method has been tested by its use for analysing NBS standard reference materials.
 ...
PMID:A continuous hydride-generation system for direct current plasma atomic-emission spectrometry (DCP-AES) Determination of arsenic and selenium. 1896 43

A chemically modified electrode (CME) containing 1-(2-pyridylazo-2-naphthol is evaluated for its ability to preconcentrate bismuth(III) prior to quantification by voltammetry. The CME approach is shown to be sufficiently sensitive for sub-nanomolar concentrations to be determinable after chemical deposition for 60 sec. Further, when the bismuth is deposited from iodide-containing sulphuric acid media, the discrimination against interference by copper(II) is significantly better than that obtained with conventional stripping analysis. The results obtained for Bi(III)( in an NBS reference solution agree well with the recommended value.
 ...
PMID:Preconcentration and determination of Bismuth (III) at a chemically modified electrode containing 1-(2-pyridylazo)-2-naphthol. 1896 11

Cadmium, lead and copper were determined in synthetic sea-water, drinking water and the NBS 1643b Trace Elements in Water standard reference material at mug/l. levels by flame atomic-absorption spectrometry after on-line preconcentration by sorbent extraction with a flow-injection system. Bonded silica with octadecyl functional groups packed in a micro column of 100 mul capacity was used to collect diethylammonium diethyldithiocarbamate complexes of the heavy metals in the aqueous samples. The sample loading time was 20 sec at a flow-rate of 3.3 ml/min. Ethanol or methanol was used to elute the adsorbed analytes into the spectrometer. The sample loading rate, elution rate and pH were optimized. Enrichment factors of 19-25 for Cd, Pb and Cu were achieved at sampling frequencies of 120/hr with precisions of 1.4, 1.0 and 1.3% rsd (n = 11), respectively. The detection limits (3sigma) for Cd, Pb and Cu were 0.3, 3 and 0.2 mug/l., respectively. Determination of Cd, Pb and Cu in NBS SRM 1643b showed good agreement with the certified values. Recoveries of Cd and Pb added to sea-water were 95 and 102%, respectively.
 ...
PMID:Determination of cadmium, lead and copper in water samples by flame atomic-absorption spectrometry with preconcentration by flow-injection on-line sorbent extraction. 1896 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>