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)

We report the determination of catecholamines (dopamine, norepinephrine, and epinephrine) and their 3-O-methylated metabolites (3-methoxytyramine, normetanephrine, and metanephrine) in urine by gas chromatography/mass spectrometry, with use of stable isotopically labeled internal standards. Normal excretion values in terms of creatinine, expressed as a function of age, are given, together with results obtained for patients with neuroblastoma, ganglioneuroblastoma, pheochromocytoma, parkinsonism treated with L-DOPA plus peripheral decarboxylase inhibitor, and a patient with cardiogenic shock treated with dopamine. The results obtained for normal adults are discussed in relation to other catecholamine metabolites and mean overall catecholamine turnover.
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PMID:Determination of catecholamines and their 3-O-methylated metabolites in urine by mass fragmentography with use of deuterated internal standards. 26 88

We describe the determination of the 4-O-methylated catecholamine metabolites 4-methoxy-3-hydroxyphenylacetic acid (iso-HVA), 4-methoxy-3-hydroxyphenylmandelic acid (iso-VMA) and 4-methoxy-3-hydroxyphenylethylene glycol (iso-MOPEG) in urine with use of mass fragmentography and deuterated internal standards. Normal values, expressed in terms of creatinine, are given as a function of age. Urinary excretion values during neuroblastoma, pheochromocytoma, and parkinsonism treated with L-DOPA, and during the intravenous administration of dopamine are discussed. For normal persons, the mean percentages (+/- SD) of 4-O-methylated metabolites relative to their 3-O-methylated analogs were 6.29 +/- 2.79% (iso-HVA/HVA), 0.70 +/- 0.57% (iso-VMA/VMA), and 0.77 +/- 0.53% (iso-MOPEG/MOPEG). We observed no significant changes in these parameters for the patients studied and conclude that the determination of 4-O-methylated catecholamine metabolites for these patients does not add information to the results obtained from their quantitatively more important 3-O-methylated analogs.
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PMID:Determination of 4-O-methylated catecholamine metabolites in urine by mass fragmentography. 47 19

We report the determination of 3-methoxy-4-hydroxyphenylpyruvic acid, 3,4-dihydroxyphenylmandelic acid, and 3,4-dihydroxyphenylethylene glycol in urine, by use of gas chromatography/mass spectrometry in combination with a simple purification method and deuterium-labeled internal standards. Normal excretion values in terms of creatinine, expressed as a function of age, are given, together with results obtained for patients with neuroblastoma, pheochromocytoma, or parkinsonism treated with L-DOPA + peripheral decarboxylase inhibitor, and for a patient receiving dopamine. We were unable to identify 3, 4-dihydroxyphenyllactic acid in urine. The results obtained and their relation to other catecholamine metabolites and catecholamine-precursor metabolites in urine are discussed.
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PMID:Determination of 3-methoxy-4-hydroxyphenylpyruvic acid, 3,4-dihydroxyphenylethylene glycol, and 3,4-dihydroxyphenylmandelic acid in urine by mass fragmentography, with use of deuterium-labeled internal standards. 70 35

The toxic effect of the Parkinsonism-producing neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was investigated using a neuronal cell culture system, namely, neuroblastoma X glioma hybrid NG 108-15. The cells were able to metabolize MPTP into its active metabolite MPP+ (1-methyl-4-phenylpyridinium ion) and to convert its derivative, 2'-methyl MPTP, to the corresponding pyridinium ion. Degenerative changes were observed in NG 108-15 cells when they were examined with a phase-contrast microscope following exposure to MPTP, MPP+, or 2'-methyl MPTP. These compounds also caused an increased leakage of LDH from the treated cells. An enhanced release of [14C]adenine nucleotides was observed from treated cells which were prelabeled with [14C]adenine. The cell death as indicated by the leakage of LDH and the release of adenine nucleotides was markedly reduced in the presence of a high concentration (25 mM) of glucose in the medium. MPTP and MPP+ induced a drastic depletion in cell ATP content prior to cell death. The ATP depletion was also reduced by the presence of a high concentration of glucose. In contrast, tetraphenylborate, a lipophilic anion, highly potentiated the ATP depletion and the subsequent cell death induced by MPTP. Thus, ATP depletion could be a major factor in MPTP-induced neuronal cell death.
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PMID:MPTP-induced ATP depletion and cell death in neuroblastoma X glioma hybrid NG 108-15 cells: protection by glucose and sensitization by tetraphenylborate. 199 18

We have developed a routine capillary gas-chromatographic profiling method for simultaneous quantitative determination of the tert-butyldimethylsilyl derivatives of homovanillic acid, vanilmandelic acid, 3-methoxy-4-hydroxyphenylethylene glycol, and 3,4-dihydroxyphenylacetic acid and the estimation of 5-hydroxyindole-3-acetic acid in urine. The method is useful for diagnosis and followup of patients with functional tumors characterized by increased urinary excretion of metabolites originating from the metabolism of tyrosine and tryptophan--e.g., neuroblastoma, pheochromocytoma, carcinoid, and melanoma. It may also be applicable in pharmacokinetic studies of administered aromatic amino acids (parkinsonism, mental diseases, loading tests) and for diagnosis and followup of patients with inborn errors of metabolism that are characterized by organic aciduria (for instance, tyrosyluria and phenylketonuria).
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PMID:Simultaneous determination of the four major catecholamine metabolites and estimation of a serotonin metabolite in urine by capillary gas chromatography of their tert-butyldimethylsilyl derivatives. 746 Feb 71

Calcium channel antagonists are drugs currently used in the treatment of neurological and cardiovascular disorders and occasionally produce parkinsonism and movement disorders as a side effect. We investigated the effects of calcium channel antagonists on the pharmacology of dopamine systems in vivo and in vitro. Flunarizine, cinnarizine, and diltiazem reduce the viability of dopamine-rich human neuroblastoma cells in vitro. These compounds plus verapamil, nifedipine, and nicardipine reduce 3H-spiperone binding to bovine striatal membranes, 3H-dopamine uptake, K(+)-induced 3H-dopamine release, and apomorphine-induced rotation, but not amphetamine-induced rotation, in 6-OH-dopamine-lesioned rats. Therefore, all calcium channel antagonists tested reduce dopamine neurotransmission in vitro and in vivo, whereas the evidence of toxicity for dopamine cells in vitro is restricted to flunarizine, cinnarizine, and diltiazem. The clinical relevance of these toxic effects may depend on several factors, including age, penetration across the blood-brain barrier, and types of calcium channels present in the different neuronal subtypes. On the other hand, the finding of dopamine-regulating properties not associated to neurotoxic effects in the dihydropyridines and verapamil provides new putative therapeutics tools for the treatment of neurologic disorders associated with dopamine hyperactivity.
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PMID:Effects of calcium antagonists on the dopamine system. 866 55

The uptake and cytotoxicity of 1-methyl-4-phenylpyridinium (MPP+), the toxic metabolite of the parkinsonism inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were studied in COS-7 cells transiently transfected with the cloned human noradrenaline and dopamine transporters and in permanently transfected SK-N-MC neuroblastoma cells. MPP+ had a 10- to 20-fold lower K(m) value for the noradrenaline than for the dopamine transporter. In dopamine transporter expressing cells, the maximal transport rate (Vmax) of MPP+, dopamine and noradrenaline was the same, but in noradrenaline transporter expressing cells the Vmax of MPP+ and dopamine was only one-half of the Vmax of noradrenaline. The turnover numbers (Vmax of uptake/maximal binding sites of binding) were 5 times higher for the dopamine transporter (as measured with [3H]dopamine and [3H]-2 beta-carbomethoxy-3 beta-(4-fluorophenyl) tropane than for the noradrenaline transporter (as measured with [3H]noradrenaline and [3H]nisoxetine). In SK-N-MC cells with similar Vmax values for both catecholamines, noradrenaline transporter expressing cells were killed by lower concentrations of MPP+ in the medium than dopamine transporter expressing cells. Desipramine blocked the toxicity of MPP+ toward the noradrenaline transporter, but not the dopamine transporter expressing cells. We conclude that the toxic effect of MPTP at the striatal dopamine system in the MPTP primate model of Parkinson's disease is not correlated with the affinity profile of MPP+ for catecholamine transporters, but rather with the higher turnover number of MPP+ at the dopamine transporter. In contradistinction, the toxicity of MPTP at the noradrenaline neurons in the primate cerebral cortex (Pifl et al., 1991) may involve the higher affinity of MPP+ for the noradrenaline transporter.
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PMID:Catecholamine transporters and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity: studies comparing the cloned human noradrenaline and human dopamine transporter. 866 8

Apoptosis has been shown to be induced by some pathological stimuli. MPP+ is a neurotoxin and an inducer of parkinsonism. When SH-SY5Y cells, human neuroblastoma cell line, were treated with MPP+, cell death estimated by lactate dehydrogenase (LDH) leakage assay occurred. The cell death was associated with the DNA fragmentation into nucleosomal fragments at 180 bp, suggesting that MPP(+)-induced cell death of SH-SY5Y cells occurs through apoptosis. Although SH-SY5Y cells natively express Bcl-2 protein, which inhibits apoptosis, the level of Bcl-2 protein in SH-SY5Y cells increased with increases in the treatment periods of MPP+. MPP+ inhibits the mitochondrial respiratory chain. The other inhibitors of the mitochondrial respiratory chain, antimycin A and oligomycin, also caused cell death associated with DNA fragmentation, but did not increase the Bcl-2 protein level, suggesting that an MPP(+)-induced apoptosis may be due to the inhibition of the mitochondrial respiratory chain but the MPP(+)-induced increase in the Bcl-2 protein level is not due to it. A protein kinase inhibitor, staurosporine, inhibited the MPP(+)-induced increase in the Bcl-2 protein level, but not the MPP(+)-induced cell death. These results also suggest that the mechanism by which MPP+ increases the Bcl-2 protein level is different from that of MPP(+)-induced cell death.
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PMID:1-methyl-4-phenyl-pyridinium ion (MPP+) causes DNA fragmentation and increases the Bcl-2 expression in human neuroblastoma, SH-SY5Y cells, through different mechanisms. 878 20

Endogenous isoquinolines with and without catechol structure have been proposed to be neurotoxins specific for dopamine neurons. In this paper they were examined for the cytotoxicity of human dopaminergic neuroblastoma SH-SY5Y cells. The cytotoxicity was quantitatively determined using Alamar Blue assay, by which the reduction-oxidation potency in the living cells can be measured spectrometrically. 1,2-Dimethyl-6,7-dihydroxyisoquinolinium ion [1,2-DMDHIQ+], an oxidation product of a parkinsonism-inducing isoquinoline, 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahroisoquinoline [N-methyl-(R)salsolinol, NM(R)Sal] was found to be the most potent toxin among isoquinolines examined. In general, catechol isoquinolines were more toxic than isoquinolines without catechol structure. With and without catechol structure, the oxidized isoquinolinium ion having methyl groups at C-1 and N-2 positions proved to be more cytotoxic than the simple isoquinolines. The involvement of 1,2-DMDHIQ+ to the neurotoxicity of NM(R)Sal was suggested and discussed.
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PMID:Cytotoxicity of endogenous isoquinolines to human dopaminergic neuroblastoma SH-SY5Y cells. 908 93

A dopamine-derived 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydrosioquinoline [N-methyl-(R)salsolinol] was found to occur enantioselectively in human brain. This isoquinoline induced parkinsonism in rat after injection in the striatum, and the behavioral, biochemical and pathological changes were very similar to those in Parkinson's disease. N-Methyl-(R)salsolinol depleted dopamine neurons in the rat substantia nigra without necrotic tissue reaction, which may be due to the apoptotic death process, as proved by its induction of DNA damage in dopaminergic neuroblastoma SH-SY5Y cells. N-Methyl-(R)salsolinol was found to increase significantly in the cerebrospinal fluid of parkinsonian patients. All these results suggest that N-methyl-(R)salsolinol may be an endogenous neurotoxin to cause Parkinson's disease and the enzymes involved in its biosynthesis and catabolism may be endogenous factors in the pathogenesis of this disease.
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PMID:N-methyl-(R)salsolinol as a dopaminergic neurotoxin: from an animal model to an early marker of Parkinson's disease. 912 Apr 28


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