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 interactions of nitric oxide (NO) and ascorbate were explored on the control of growth of human brain tumor cells. Sodium nitroprusside, a NO-generating agent, inhibited the growth of SK-N-MC human neuroblastoma cells in a dose-dependent manner. The growth inhibitory effect of nitroprusside was potentiated by sodium ascorbate and inhibited by hemoglobin. Ascorbate-induced potentiation was also observed in U-373 MG human astrocytoma cells. In both tumor cell lines, this potentiation was blocked by catalase, suggesting that hydrogen peroxide may be involved in the potentiation mechanism. In astrocytoma cells, mannitol or deferoxamine also reversed ascorbate-induced potentiation, indicating involvement of hydroxyl radical. These results suggest that the combined treatment with nitroprusside and ascorbate may be a valuable therapeutic strategy for brain tumors.
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PMID:Potentiation of anti-proliferative effect of nitroprusside by ascorbate in human brain tumor cells. 818 Sep 63

We examined the effects of 6-hydroxydopamine (6-OHDA) treatment on the human neuroblastoma cell line SK-N-SH-SY5Y (SY5Y) and the rat pheochromocytoma cell line, PC12. Structural and metabolic integrity was tested by measuring the ability of cells to transport the non-metabolizable amino acid analogue [3H]-alpha-aminoisobutyric acid (AIB). We determined that treatment with 6-OHDA at concentrations of 49 microM and 62 microM inhibited 50% of the AIB uptake in SY5Y and PC12 cells, respectively. Inhibition of AIB uptake was prevented by the addition of catalase, but was not influenced by the addition of 1 mM dopamine. This indicated that cell damage resulted from the generation of H2O2 and was independent of the catecholamine uptake system. Effects directly on the catecholamine uptake system were observed by measuring the uptake of 3H-dopamine. In contrast to the effects on amino acid uptake, dopamine uptake was significantly inhibited by 6-OHDA treatment, and this inhibition was not prevented by the addition of catalase. The results indicate a Ki of 430 microM for inhibition of dopamine uptake by 6-OHDA treatment of PC12 cells. The results are consistent with a competitive irreversible inhibition of the dopamine uptake sites by 6-OHDA or one of its metabolites. Thus, the lack of a catecholamine uptake-dependent cellular toxicity appears to result from the direct inactivation of catecholamine uptake sites. Similarly, the inhibition of dopamine uptake in vivo by 6-OHDA may be explained, at least in part, by direct inactivation of dopamine uptake sites rather than exclusively by intracellular transport and action of 6-OHDA.
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PMID:Competitive irreversible inhibition of dopamine uptake by 6-hydroxydopamine. 845 41

The study of oxygen radical generation and effects during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) metabolism was undertaken in an in vitro test system. Three neurochemically discrete neuronal cell lines, B50 (cholinergic) and B65 rat cell lines and SKNSH human neuroblastoma (both catecholaminergic), were exposed to MPTP (0-200 microM). Parallel experiments were performed using reagent H2O2, an intermediate which may be generated during MPTP metabolism, to determine whether MPTP and H2O2 had any selectivity of toxicity and whether the mechanisms of cell death were similar. MPTP toxicity was shown to be reduced by monoamine oxidase B inhibitors, pargyline (P < 0.01) and selegiline (P < 0.05), indicating that toxicity was due to metabolism of MPTP rather than the parent compound. Cytotoxicity was also decreased in the presence of antioxidants, most notably in the presence of superoxide dismutase and catalase together (P < 0.01), suggesting that reactive oxygen species (ROS) play a role in MPTP-induced cell death. Attempts to determine the intracellular target for oxidative attack did not identify significant levels of lipid peroxidation products, but did demonstrate nucleoid expansion, possibly the result of double stranded DNA breaks induced by ROS.
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PMID:An investigation into the role of reactive oxygen species in the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity using neuronal cell lines. 845 68

The effects of intracellularly generated H2O2 on cell viability, morphology, and biochemical markers of injury have been investigated in a clonal cell line of neuronal origin (140-3, mouse neuroblastoma X rat glioma) as a cell culture model for the role of oxidative stress in the long-term loss of neurons in the brain. The H2O2 was generated from the redox cycling of menadione, or by the oxidation of serotonin catalyzed by monoamine oxidase, to simulate the effect of amine neurotransmitter turnover. Incubation with menadione at concentrations as low as 10 microM for several hours resulted in significant losses of cell viability and altered morphology. Similar effects were evident in the presence of serotonin only after incubation overnight with concentrations > 1 mM. The cytotoxicity of either agent was potentiated by preincubation with specific inhibitors of two enzymes important to cellular antioxidant defenses, 3-amino-1,2,4-triazole for catalase and 1,3-bis(chloromethyl)-1-nitrosourea for glutathione reductase. Activity of another antioxidant enzyme of particular importance to antioxidant defenses in brain, the selenoprotein glutathione peroxidase, was stimulated fourfold by growth of cultures in the presence of sodium selenite as a source of active-site Se for the enzyme. The only effect of the selenite on other functionally coupled antioxidant enzymes was a decrease in activity of superoxide dismutase at concentrations > 200 nM. The selenite substantially protected cells against oxidative stress induced by combinations of menadione, 3-amino-1,2,4-triazole, and 1,3-bis(chloromethyl)-1-nitrosourea, but was only marginally effective with serotonin as a source of oxidative stress. The monoamine oxidase inhibitor pargyline increased cell survival in the presence of serotonin, demonstrating the role of this enzyme in its cytotoxicity. DNA damage (single strand breaks), but not lipid peroxidation, correlated with the cytotoxic effects of menadione.
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PMID:Oxidative stress in a clonal cell line of neuronal origin: effects of antioxidant enzyme modulation. 849 17

We studied heat shock protein (HSP) synthesis by cultured human neuroblastoma cells in response to either hyperthermia or high levels of superoxide anion (oxygen free radical). Both treatment modalities resulted in induced synthesis of the same major HSP species with an additive effect on the latter and on cell growth inhibition upon combined treatments. Exposure to superoxide anion in the presence of the free radical scavenging enzymes, superoxide dismutase and catalase improved cell survival and prevented HSP induction. These findings suggest a common mechanism by which various forms of injury, such as hyperthermia, cause HSP induction, that is, via oxidative stress or increased production of oxygen free radicals. Increased expression of some HSPs has been detected in association with the pathological lesions that characterize some neurodegenerative diseases such as the neurofibrillary tangles of Alzheimer's disease. This, in turn, suggests that chronic oxidative stress may play a role in the pathogenesis of these disorders.
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PMID:Oxygen free radicals as inducers of heat shock protein synthesis in cultured human neuroblastoma cells: relevance to neurodegenerative disease. 849 94

Enhanced oxidative stress has been suggested to be involved in the degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease. The high turnover rate of dopamine and/or unsequestered dopamine may cause an increase of formation of hydrogen peroxide via either oxidative deamination of dopamine by monoamine oxidase or autoxidation. Hydrogen peroxide would be converted to more toxic hydroxyl free radicals. L-beta-3,4-Dihydroxyphenylalanine hydrochloride (L-DOPA), the most useful drug in the symptomatic treatment of Parkinson's disease, has been considered to possess deteriorating degenerative side-effects. The catecholaminergic neuroblastoma SH-SY5Y cells were chosen to investigate the cytotoxic effect of dopamine and L-DOPA. Both dopamine and L-DOPA were found to be cytotoxic towards SH-SY5Y cells. Such toxic effects were accompanied by an increase of oxidative stress in the cell cultures and could be reversed effectively by catalase and to a lesser extent by superoxide dismutase. The non-enzymatic antioxidants L-ascorbic acid, glutathione, N-acetyl-L-cysteine, but not (+)-alpha-tocopherol, also completely protected SH-SY5Y cells against the cytotoxic effects induced by dopamine and L-DOPA. Antioxidative factors, namely free radical scavengers (including N-tert-butyl-alpha-phenylnitrone, salicylic acid, and D-mannitol) and a strong iron chelator, deferoxamine, however, did not protect the SH-SY5Y cells against dopamine and L-DOPA. The generation of reactive oxygen species and the resulting enhanced oxidative stress was clearly involved in the dopamine- and L-DOPA-induced cytotoxic effects. Hydrogen peroxide played the most important role related to cytotoxicity of dopamine and L-DOPA.
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PMID:Dopamine- and L-beta-3,4-dihydroxyphenylalanine hydrochloride (L-Dopa)-induced cytotoxicity towards catecholaminergic neuroblastoma SH-SY5Y cells. Effects of oxidative stress and antioxidative factors. 906 40

Stimulation of human SH-SY5Y neuroblastoma cells by a muscarinic receptor agonist, carbachol (CCh; 1 mM), elevated levels of free intracellular calcium and subsequently increased the production of reactive oxygen species (ROS). Quinuclidinylbenzilate (QNB) binding increased at 1 h after CCh, but returned back to the control level at 3 h. Production of ROS increased, however, during the 3 h time period. CCh also increased the translocation of protein kinase C (PKC) to the membrane. ROS production was completely blocked by atropine and a PKC inhibitor, Ro 31-8220. These results show that increased ROS production was a result of muscarinic receptor stimulation, and that PKC had an active role in this cellular stimulation. ROS production upon cellular stimulation by CCh was completely inhibited also by superoxide dismutase, and partially by catalase, indicating that the formation of superoxide anion dominated in cholinergic-induced generation of ROS in human neuroblastoma cells. These results also show that muscarinic stimulation causes sustained ROS production in human neuroblastoma cells. The slow increase in ROS production by CCh suggest a stepwise cascade of events leading to oxidative stress with a triggering role of cholinergic muscarinic receptors in this process.
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PMID:Cholinergic-induced production of reactive oxygen species in human neuroblastoma cells. 915 1

We report the effects of meta-iodobenzylguanidine (MIBG), a neuroblastoma-seeking agent, on cell proliferation and several oxidative stress-related parameters in the human neuroblastoma cell line SK-N-BE(2c). MIBG inhibited the proliferation of this cell line in micromolar concentrations. Measurements of the malondialdehyde (MDA) concentrations (a measure of the extent of lipid peroxidation) of cells treated with MIBG showed that increasing concentrations of MIBG led to an increase in MDA levels of the cells. This effect was most pronounced after one day of cellular exposure to MIBG and disappeared after 3 days. Disappearance of the elevated MDA levels caused by MIBG is probably the result of increased activity of the H2O2 detoxifying enzymes, catalase and glutathion peroxidase (GPx). The catalase- and GPx-enzyme activity of cells exposed to MIBG steadily increased with time, reaching a maximum after 4 days. Oxidative stress caused by MIBG thus at first leads to cellular damage (lipid peroxidation) but over a longer period does not lead to decreased proliferation rate of the cells, most likely because of cellular adaptation to increased oxidative stress by up-regulation of the H2O2 detoxifying enzymes catalase and GPx.
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PMID:MIBG causes oxidative stress and up-regulation of anti-oxidant enzymes in the human neuroblastoma cell line SK-N-BE(2c). 924 93

Dopamine (DA) is oxidized to the neurotoxic prooxidant species H2O2, OH., and DA quinones. We tested whether dimethyl fumarate (DMF), an electrophile shown to induce a pleiotropic antioxidant response in nonneuronal cells, could reduce the toxicity of DA metabolites in neural cells. Treatment of the N18-RE-105 neuroblastoma-retina hybridoma cell line with 30-150 microM dopamine led to cell death within 24 h, which increased steeply with dose, decreased with higher plating density, and was blocked by the H2O2-metabolizing enzyme catalase. Pretreatment with DMF (30 microM, 24 h) significantly attenuated DA and H2O2 toxicity (40-60%) but not that caused by the calcium ionophore ionomycin. DMF treatment also elevated total intracellular GSH and increased activities of the antioxidant enzymes quinone reductase (QR), glutathione S-transferase (GST), glutathione reductase, and the pentose phosphate enzyme glucose-6-phosphate dehydrogenase. To assess the protective efficacy of QR and GST, a stable cell line was constructed in which these enzymes were overexpressed. Cell death in the overexpressing line was not significantly different from that in a cell line expressing normal QR and GST activities, indicating that these two enzymes alone are insufficient for protection against DA toxicity. Although the relative importance of a single antioxidant enzyme such as QR or GST may be small, antioxidant inducers such as DMF may prove valuable as agents that elicit a broad-spectrum neuroprotective response.
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PMID:Activation of endogenous antioxidant defenses in neuronal cells prevents free radical-mediated damage. 964 52

The mechanism of the cytotoxicity of endogenous dopamine-derived (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-N-methylsalsolinol] to differentiated human dopaminergic neuroblastoma SH-SY5Y cells was studied using a reduction-oxidation indicator, Alamar Blue. N-Methylsalsolinol and its oxidation product, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, were found to inhibit oxidative phosphorylation, as shown by the Redox capacity. Antioxidants, such as reduced glutathione, catalase, Tris and n-propyl gallate, reduced the cytotoxicity of N-methylsalsolinol, suggesting that hydroxyl radical was the major reactive oxygen species for the cytotoxicity. Deprenyl also protected the cells from the decrease of the Redox capavity by N-methylsalsolinol. However, antioxidants did not protect the cells from the cytotoxicity of the catechol isoquinolinium ion. The results suggest that oxidative stress induced by hydroxyl radical may be involved in the cell death of dopaminergic neurons by N-methylsalsolinol.
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PMID:Generation of reactive oxygen species accounts for cytotoxicity of an endogenous dopaminergic neurotoxin, (R)-N-methylsalsolinol, to differentiated dopaminergic SH-SY5Y cells. 972 Sep 69


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