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)

A variety of compounds derived from garlic bulbs have been shown in animal systems to possess anticancer properties. However, little information is available regarding the effectiveness of garlic in the prevention or treatment of human cancers. In the current study, we have assessed the ability of S-allyl cysteine (SAC), a derivative of aged garlic extract, to affect the proliferation and differentiation of LA-N-5 human neuroblastoma cells in vitro. Time-and dose-dependent inhibition of cell grow was observed in cultures treated with SAC for at least 2 days, with a half-maximal response at approximately 600 micrograms/ml. SAC treatment was unable to induce differentiation in neuroblastoma cells as assessed by morphological, biochemical and molecular markers. In addition, SAC was unable to potentiate the effects of retinoic acid and 8-bromo-cyclic AMP, agents known to promote differentiation of LA-N-5 cells. Our results indicate that SAC can inhibit human neuroblastoma cell growth in vitro. However, the apparent inability of this compound to induce differentiation may limit its therapeutic potential.
 ...
PMID:Antiproliferative effect of the garlic compound S-allyl cysteine on human neuroblastoma cells in vitro. 134 4

Na(+)-dependent amino isobutyric acid transport by two neuroblastoma cell lines with and without amplification of the oncogene N-myc is studied. Surprisingly, the contribution of system A is greater in the cell line showing no N-myc amplification. Preliminary data support a role for essential tyrosine and cysteine residues in the active center of the carriers, mainly in system A.
 ...
PMID:Na(+)-dependent AIB transport by neuroblastoma cells. 145 99

Site-directed mutagenesis was used to study the cysteine residue involved in the assembly of human acetylcholinesterase (HuAChE) catalytic subunits. Substitution of the cysteine at position 580 by alanine resulted in impairment of interchain disulfide bridge formation; the mutagenized enzyme (C580A) was secreted from recombinant cells in the monomeric form and failed to assemble into dimers. The mutant monomeric HuAChE did not differ from the native oligomeric enzyme neither in rate of catalysis nor in affinity to acetylthiocholine. Mutant monomers were also shown to retain the acetylcholinesterase characteristic sensitivity to high substrate concentrations. The mutation did not seem to affect the efficiencies of either synthesis or secretion of recombinant HuAChE polypeptides, as was demonstrated in cell lines derived from human embryonic kidney (293 cells) as well as from a human neuroblastoma (SK-N-SH). Furthermore, the mutation did not lead to an increase in accumulation of intracellular HuAChE polypeptides, suggesting that export of acetylcholinesterase from cells may not be coupled to subunit assembly.
 ...
PMID:The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant. 174 70

1. Dimethylsulfoxide-induced differentiated neuroblastoma express high levels of membrane 21 to 23-kDa carboxyl methylated proteins. Relationships among methylation, isoprenylation, and GTP binding in these proteins were investigated. Protein carboxyl methylation, protein isoprenylation, and [alpha-32P]GTP binding were determined in the electrophoretically separated proteins of cells labeled with the methylation precursor [methyl-3H]methionine or with an isoprenoid precursor [3H]mevalonate. 2. A broad band of GTP-binding proteins, which overlaps with the methylated 21 to 23-kDa proteins, was detected in [alpha-32P]GTP blot overlay assays. This band of proteins was separated in two-dimensional gels into nine methylated proteins, of which four bound GTP. 3. The carboxyl-methylated 21 to 23-kDa proteins incorporated [3H]mevalonate metabolites with characteristics of protein isoprenylation. The label was not removed by organic solvents or destroyed by hydroxylamine. Incorporation of radioactivity from [3H]mevalonate was enhanced when endogenous levels of mevalonate were reduced by lovastatin, an inhibitor of mevalonate synthesis. Lovastatin blocked methylation of the 21 to 23-kDa proteins as well (greater than 70%). 4. Methylthioadenosine, a methylation inhibitor, inhibited methylation of these proteins (greater than 80%) but did not affect their labeling by [3H]mevalonate. The results suggest that methylation of the 21 to 23-kDa proteins depends on, and is subsequent to, isoprenylation. The sequence of events may be similar to that known in ras proteins, i.e., carboxyl methylation of a C-terminal cysteine that is isoprenylated. 5. Lovastatin reduced the level of small GTP-binding proteins in the membranes and increased GTP binding in the cytosol. Methylthioadensoine blocked methylation without affecting GTP binding. 6. Thus, isoprenylation appears to precede methylation and to be important for membrane association, while methylation is not required for GTP binding or membrane association. The role of methylation remains to be determined but might be related to specific interactions of the small GTP-binding proteins with other proteins.
 ...
PMID:Relationship among methylation, isoprenylation, and GTP binding in 21- to 23-kDa proteins of neuroblastoma. 175 64

The cytotoxicity of dopamine (DA) and 6-hydroxydopamine (6-OHDA) on living cells, in vitro, has been previously deeply investigated in neuroblastoma cells. This study was designed to explore the possibility to use bacteria as targets for studying DA and 6-HODA cytotoxicity. Both DA and 6-HODA oxidize when added to bacteriological media. The rate of autoxidation of 6-HODA was greater than DA within the first hours. The oxidation-dependent cytotoxicity caused bacterial growth-inhibition and killing at concentration of 10(-4)M. All the bacterial strains tested were slightly more susceptible to DA than to 6-HODA. Antioxidants (sodium metabisulfite, cysteine) prevented the oxidation and abolished the growth-inhibitory activity. The addition of exogenous catalase protected the cells against the effect of the oxidation of both the catecholamines up to the concentration of 5 mM, while the addition of exogenous superoxide dismutase protected the cells only at the minimal inhibitory concentrations. Taking into account that some of the results obtained are similar to those previously reported using neuroblastoma cells as targets, the use of bacteria for studying oxygen toxicity from these catecholamines seems to be a potentially useful model system.
 ...
PMID:An in vitro bacterial model of cytotoxicity to living cells caused by dopamine and 6-hydroxydopamine oxidation at physiological pH. 190 28

To investigate the biochemical nature of temperature-induced high-affinity [3H]tryptamine binding sites, we subjected whole rat brain synaptic membranes to treatment with various protein-modifying reagents and examined the subsequent [3H]tryptamine binding properties of the membranes. Pretreatment of the membrane preparations with NEM, NBS, PCMB, PAPMA and MA, but not with iodoacetamide, DTT, glutathione and cysteine, reduced the [3H]tryptamine binding. In addition, to at least approx. 10(-4) M, the inactivation properties of NEM, PCMB, PAPMA and MA, except for NBS, were temperature-dependent. Furthermore, it was revealed that the Scatchard plot of [3H]tryptamine binding in membranes pretreated with these thiol reagents conformed to a curved line, as well as in the case of the control membranes. Nonlinear regression analysis of these data showed that NEM decreased the Bmax values of both the high and low affinity binding sites with no significant alteration in the KD values, whereas PCMB, PAPMA and MA increased only the KD value of the high affinity sites, accompanying the decrease of the Bmax values of both sites. These results indicate that the temperature-induced high-affinity [3H]tryptamine binding molecule(s) is a thiol protein.
 ...
PMID:Effects of protein-modifying reagents on brain tryptamine binding sites: possible involvement of a thiol group in temperature-induced high-affinity [3H]tryptamine binding sites. 196 19

A novel human brain complementary DNA sequence encodes n-chimaerin, a 34,000 Mr protein. A single cysteine-rich sequence CX2CX13CX2CX7CX7C in the N-terminal half of n-chimaerin shares almost 50% identity with corresponding sequences in the C1 regulatory domain of protein kinase C. The C-terminal half of n-chimaerin has 42% identity with the C-terminal region (amino acid residues 1050 to 1225) of BCR, the product of the breakpoint cluster region gene involved in Philadelphia (Ph') chromosome translocation. n-Chimaerin mRNA (2.2 x 10(3) base-pairs) is specifically expressed in the brain, with the highest amounts being in the hippocampus and cerebral cortex. The mRNA has a neuronal distribution and is expressed in neuroblastoma cells, but not in C6 glioma or primary astrocyte cultures. The similarity of two separate regions of n-chimaerin to domains of protein kinase C and BCR has intriguing implications with respect to its evolutionary origins, its function in the brain and potential phorbol-ester-binding properties.
 ...
PMID:Novel human brain cDNA encoding a 34,000 Mr protein n-chimaerin, related to both the regulatory domain of protein kinase C and BCR, the product of the breakpoint cluster region gene. 229 65

Neuronal nicotinic receptors (nAchRs) have been isolated or cloned in insect, bird and mammalian neurons, but no information exists on the primary structure of human neuronal nAchRs. By screening a cDNA library from the human neuroblastoma cell line IMR 32 with a cDNA probe corresponding to the full length of rat alpha 3-nicotinic subunit, we have identified an open reading frame encoding a protein of 502 amino acids. This protein shows all the features of members of the ligand-gated receptor superfamily and has two cysteine residues at positions 192, 193 which are typical of the nicotinic alpha-subunits. Because of its high homology to rat alpha 3 (93% amino acid identity), we conclude that we have cloned the human alpha 3-nicotinic subunit.
 ...
PMID:Molecular cloning of human neuronal nicotinic receptor alpha 3-subunit. 233 8

Metallothioneins are a class of cysteine-rich and low molecular weight, metal-binding proteins that are inducible by a wide variety of agents, including metal ions, such as cadmium and zinc, glucocorticoid hormones, interferon, and tumor promoters. In an effort to delineate the regulation of the synthesis of the recently identified brain metallothionein-like protein, a study was undertaken to compare the induction of metallothionein in human neuroblastoma IMR-32 cells by zinc, cadmium, and dexamethasone using the human Chang liver cells as a control. Both cadmium (1 microM) and zinc (100 microM) significantly enhanced the incorporation of [35S]cysteine into metallothioneins isolated from both neuroblastoma and Chang liver cells. Dexamethasone in concentrations of 10 microM stimulated the synthesis of metallothionein in the Chang cells, whereas it had no effects on the synthesis of metallothionein in the neuroblastoma cells at concentrations ranging from 2.5--100 microM. The degree of stimulation of metallothionein synthesis in the Chang cells by cadmium and zinc was significantly higher than seen in neuroblastoma cells. The neuroblastoma IMR-32 exhibited less tolerance to the toxicity of both cadmium and zinc than the Chang cells, which may correlate with the inherent ability of these ions to induce metallothioneins in these dissimilar cells. The results of these studies are interpreted to indicate that the factors regulating the synthesis of metallothioneins in the Chang and neuroblastoma cells are not identical, suggesting also of the presence of dissimilar regulatory mechanisms in the liver and brain.
 ...
PMID:The stimulation of metallothionein synthesis in neuroblastoma IMR-32 by zinc and cadmium but not dexamethasone. 248 8

Two dynorphin-degrading cysteine proteases, I and II, were extracted with Triton X-100 from neuroblastoma cell membrane, isolated from accompanying dynorphin-degrading trypsin-like enzyme by affinity chromatography on columns of soybean trypsin inhibitor-immobilized Sepharose and p-mercuribenzoate-Sepharose, and separated by ion-exchange chromatography on diethylaminoethyl (DEAE)-cellulose and TSK gel DEAE-5PW columns. Cysteine protease II was purified further by hydroxyapatite chromatography and gel filtration. The molecular weights of cysteine proteases I and II were estimated to be 100,000 and 70,000, respectively, by gel filtration. Both of the enzymes, were inhibited by p-chloromercuribenzoate, N-ethylmaleimide, and high-molecular-weight kininogen, but not or only slightly inhibited by diisopropylphosphorofluoridate, antipain, leupeptin, E-64, calpain inhibitor, and phosphoramidon. Cysteine protease I cleaved dynorphin(1-17) at the Arg6-Arg7 bond with the optimum pH of 8.0, whereas II cleaved dynorphin(1-17) at the Lys11-Leu12 bond and the Leu12-Lys13 bond with the optimum pH values of 8.0 and 6.0, respectively. These bonds corresponded to those that had been proposed as the initial sites of degradation by neuroblastoma cell membrane. Cysteine protease I was further found to show strict specificity toward the Arg-Arg doublet, when susceptibilities of various peptides containing paired basic residues were examined as substrates for the enzyme.
 ...
PMID:Characterization of cysteine proteases functioning in degradation of dynorphin in neuroblastoma cells: evidence for the presence of a novel enzyme with strict specificity toward paired basic residues. 256 12


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