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)

Brain-derived neurotrophic factor (BDNF) has recently been shown to enhance the survival of dopamine neurons in cultures derived from the embryonic rat mesencephalon. We now extend this study by demonstrating that, in addition to the effect of sustaining survival of dopaminergic neurons, BDNF also confers protection against the neurotoxic effects of 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenylpyridinium ion (MPP+). Exposure of mesencephalic cultures to either 6-OHDA or MPP+ resulted in a loss of 70-80% of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunocytochemistry. In BDNF-treated cultures, loss of TH-positive cells after exposure to either toxin was reduced to only 30%. To facilitate biochemical measurements, we studied SH-SY5Y dopaminergic neuroblastoma cells. BDNF was found to protect these cells from the dopaminergic neurotoxins, 6-OHDA and MPP+. Indicative of oxidative stress, treatment of SH-SY5Y cells with 10 microM 6-OHDA for 24 h caused a fivefold increase in the levels of oxidized glutathione (GSSG). Pretreatment with BDNF for 24 h completely prevented the rise in GSSG. Further examination revealed that BDNF increased the activity of the protective enzyme, glutathione reductase, by 100%. In contrast, BDNF had no effect on the activity of catalase. These results add further impetus to exploring the therapeutic potential of BDNF in animal models of Parkinson's disease.
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PMID:Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenylpyridinium ion toxicity: involvement of the glutathione system. 845 44

This study evaluates the role of N-hydroxylamine (NH2OH) in activating soluble guanylate cyclase in the mouse neuroblastoma clone N1E-115. It has been proposed that NH2OH is a putative intermediate in the biochemical pathway for the generation of nitric oxide (NO)/endothelium-derived relaxing factor (EDRF) from L-arginine. NH2OH caused a time- and concentration-dependent increase in cyclic GMP formation in intact cells. This response was not dependent on Ca2+. In cytosol preparations the activation of guanylate cyclase by L-arginine was dose-dependent and required Ca2+ and NADPH. In contrast, NH2OH itself did not activate cytosolic guanylate cyclase but it inhibited the basal activity of this enzyme in a concentration-dependent manner. The formation of cyclic GMP in the cytosolic fractions in response to NH2OH required the addition of catalase and H2O2. On the other hand, catalase and/or H2O2 lead to a decrease in L-arginine-induced cyclic GMP formation. Furthermore, NH2OH inhibited L-arginine- and sodium nitroprusside-induced cyclic GMP formation in the cytosol. The inhibition of L-arginine-induced cyclic GMP formation in the cytosol by NH2OH was not reversed by the addition of superoxide dismutase. These data strongly suggest that NH2OH is not a putative intermediate in the metabolism of L-arginine to an activator of guanylate cyclase.
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PMID:N-hydroxylamine is not an intermediate in the conversion of L-arginine to an activator of soluble guanylate cyclase in neuroblastoma N1E-115 cells. 167 45

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.
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PMID:An in vitro bacterial model of cytotoxicity to living cells caused by dopamine and 6-hydroxydopamine oxidation at physiological pH. 190 28

Granulocytes from healthy donors lyse human neuroblastoma cells in the ADCC-reaction using antibody MAb 14.18 directed to ganglioside GD2 present on the surface of most neuroblastoma cells. Addition of catalase, superoxide dismutase and azide do not impair this process. Granulocytes from patients with chronic granulomatous disease (CGD) kill neuroblastoma cells even better than those collected from healthy donors. These results indicate that reactive oxygen intermediates (ROI) are not involved in killing of neuroblastoma cells using MAb 14.18, and that granulocytes from patients with CGD may compensate for defects in generation of reactive oxygen intermediates by more effective oxygen-independent killing mechanisms. One patient with CGD was treated with interferon-gamma. During and after treatment, generation of ROI could not be detected and neuroblastoma cell killing was not significantly altered.
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PMID:Lysis of neuroblastoma cells by the ADCC-reaction: granulocytes of patients with chronic granulomatous disease are more effective than those of healthy donors. 250 32

We investigated whether polymorphonuclear leukocytes (PMN) are able to kill human neuroblastoma cells either directly or if coated with antibody MAb 14.18 that recognizes ganglioside GD2 present on the cell surface of most neuroblastoma cells. Neuroblastoma cells could not be destroyed directly, whereas in the antibody-dependent reaction (ADCC-reaction) they were easily eliminated. In order to answer the question whether reactive oxygen intermediates are involved in this process, chemiluminescence measurements were performed. Compared to the signals that could be measured using opsonized zymosan as stimulus, only weak CL-signals could be registered during the ADCC reaction. Pretreatment of PMN with granulocyte-macrophage colony stimulating factor (GM-CSF) enhanced the CL-signals, catalase and SOD reduced it; however, cell killing was only slightly influenced in the presence of catalase and superoxide dismutase. These data suggested that reactive oxygen compounds do not play a prominent role in the killing process. Definitive evidence for this suggestion could be obtained using PMN from a patient with chronic granulomatous disease (CGD): MAb 14.18 coated neuroblastoma cells could be killed effectively, but no CL-signal could be registered, either in the ADCC-reaction or using opsonized zymosan as stimulus.
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PMID:Effects of granulocytes on human neuroblastoma cells measured by chemiluminescence and chromium-51 release assay. 272 18

Inhibitors of arachidonate metabolism and perturbants of the oxidation-reduction state of the cell were employed to develop a pharmacologic profile for muscarinic receptor-mediated cyclic GMP formation in murine neuroblastoma cells (clone N1E-115). Several lipoxygenase inhibitors [eicosatetraynoic acid (ETYA), nordihydroguaiaretic acid (NDGA), FPL 57231, FPL 55712, BW755c, propylgallate, and AA861] blocked the elevation of [3H]cyclic GMP induced by muscarinic receptor activation. The cyclooxygenase inhibitors indomethacin and ibuprofen were two orders of magnitude less potent in blocking the muscarinic receptor-mediated [3H]cyclic GMP response than in blocking cyclooxygenase in other systems. ETYA and NDGA did not affect the muscarinic inhibition of the prostaglandin E1-mediated increases in [3H]cyclic AMP levels in N1E-115 cells. ETYA did not have a reproducible effect on the muscarinic receptor-induced release of inositol phosphates. Thus, these lipoxygenase inhibitors appeared to be selective for the effector system coupled to the low-affinity muscarinic agonist-receptor conformation, i.e. that which induces cyclic GMP formation. Other effective inhibitors of the cyclic GMP response were methylene blue, catalase, bromphenacyl bromide, retinal, dithiothreitol, quinacrine, and oxidized glutathione. The antioxidant alpha-tocopherol in the concentration range of 100 microM to 1 mM potentiated the receptor response. Arachidonic acid itself was an inhibitor of the muscarinic receptor-mediated cyclic GMP response (IC50 = 45 microM). Linoleic acid and oleic acid were less potent (IC50 = 130 and 190 microM, respectively), and stearic acid was ineffective. When arachidonic acid was air-oxidized, its inhibitory potency was increased 10-fold. Most but not all of the spontaneously-produced oxidative metabolites, separable by reverse-phase high pressure liquid chromatography, were inhibitory to the receptor response. Enzymatically synthesized 12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid inhibited the muscarinic receptor [3H]cyclic GMP response, with IC50 values of 17 and 8 microM respectively. Catalase was effective in blocking the muscarinic cyclic GMP response (IC50 = 5 microM) while having no effect on either the muscarinic receptor-induced inositol phosphate release or the reduction of cyclic AMP levels. Thus, the effector system for increasing cyclic GMP in these cells displays may of the expected characteristics for the involvement of a lipoxygenase or a related enzyme that oxidatively metabolizes arachidonate in order to activate the guanylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Blockade of N1E-115 murine neuroblastoma muscarinic receptor function by agents that affect the metabolism of arachidonic acid. 301 48

The patterns of the cytolytic effects of 6-hydroxydopamine (6-OHDA), with/without ascorbate, on C-1300 and three other cloned mouse neuroblastoma cell lines (N1E-115, NS-20, N-18) were studied in vitro. The sensitivity to 6-OHDA differed and the three cloned cell lines were more sensitive than the wild type C-1300 cell line. Ascorbate synergistically potentiated the cytolytic effect of 6-OHDA to all four cell lines. The 6-OHDA cytotoxicity was eliminated by the addition of exogenous catalase but not by addition of other oxygen free radical scavengers, thereby suggesting that the hydrogen peroxide formed might influence the cells, extracellularly. In addition, the critical time for tumor cell lysis was the first 60 min of the reaction. The cytotoxicity induced by the unmasked cyclophosphamide, 4-hydroperoxycyclophosphamide, was synergistically enhanced in the presence of a nontoxic concentration of 6-OHDA and ascorbate. These data suggest that reactive oxygen intermediates may prove to be a good tool for destroying neuroblastoma cells.
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PMID:Patterns of destruction of mouse neuroblastoma cells by extracellular hydrogen peroxide formed by 6-hydroxydopamine and ascorbate. 308 96

5-S-Cysteinyldopa, a melanin precursor, has been shown to possess selective toxicity to tumour cells in vitro and in vivo. The mechanism of cytotoxicity of the catechol was studied in comparison with L-dopa and 5-S-cysteaminyldopamine. Growth inhibition of human neuroblastoma cell line of YT-nu by 5-S-cysteinyldopa was completely depressed by addition of catalase. Superoxide dismutase and five drugs thought to scavenge hydroxyl radicals or quench singlet oxygen had little effect on the cytotoxicity. Hydrogen peroxide itself was also cytotoxic at low concns. These results indicated that hydrogen peroxide was a mediator of the cytotoxicity of 5-S-cysteinyldopa. It is suggested that reaction of the catechol with cellular superoxide radicals contributes to the production of hydrogen peroxide in addition to autoxidation. Catalase reduced the cytotoxicity of L-dopa by half, while it had no inhibitory effect on the strong cytotoxicity of 5-S-cysteaminyldopamine.
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PMID:The mechanism of toxicity of 5-S-cysteinyldopa to tumour cells. Hydrogen peroxide as a mediator of cytotoxicity. 640 13

Catalase, superoxide dismutase, and dimethylsulfoxide were tested for their ability to prevent the cytotoxic effect of 6-hydroxydopamine (6-OHDA) on the human neuroblastoma line SY5Y. Viability was measured at two time points after 6-OHDA treatment: at 3 hr by means of amino acid incorporation and at 24 hr by trypan blue dye exclusion. Survival of cells treated concomitantly with catalase (50 microgram/ml) and 6-OHDA was at least 90 per cent that of untreated controls. Cells receiving 6-OHDA alone showed less than 30 per cent survival relative to untreated controls. Superoxide dismutase (50 microgram/ml) temporarily protected cells from a high concentration of 60-OHDA. Dimethylsulfoxide treatment increased survival from the control level 24 hr after treatment with 6-OHDA. Two other cell lines (A1B1 human glial cells and CHO fibroblasts) had intermediate and high resistance to the drug, respectively, compared to the low resistance of SY5Y cells. CHO and SY5Y cells had similar responses to 6-OHDA and to H2O2 when tested at twice the molarity of 6-OHDA. Specific activities of three enzymes known to detoxify H2O2 or H2O2-generated organic hydroperoxides (catalase, glutathione S-transferase, and glutathione peroxidase) were compared in the three cell lines. Catalase activity was 2.5 times as high as in A1B1 and CHO cells as in SY5Y cells when expressed as units/mg protein and 7 times as high in units/culture dish. Other enzyme activities showed no correlation to 6-OHDA resistance.
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PMID:Participation of active oxygen species in 6-hydroxydopamine toxicity to a human neuroblastoma cell line. 705 60

The effect of 6-anilino-5,8-quinolinedione (LY83583), an inhibitor of guanylyl cyclase (GC), on the growth of human brain tumor cells (U-373 MG astrocytoma and SK-N-MC neuroblastoma) was evaluated. LY83583 inhibited the growth of these cells in a dose-dependent manner. This growth inhibition was found to be the result of decreased cell viability as assessed by the trypan blue exclusion method. The LY83583-induced decrease in cell viability was not altered by dibutyryl cyclic GMP, but significantly was reversed by superoxide dismutase and catalase, indicating that these effects of LY83583 may not be due to the inhibition of GC, but due to the formation of superoxide anion. The LY83583-induced decrease in cell viability was potentiated by cotreatment with sodium nitroprusside (SNP), a nitric oxide (NO) donor. This SNP-induced potentiation was significantly blocked by various scavengers for hydroxyl radicals or by intracellular Ca2+ release blockers. These results suggest that the potentiation effects of SNP may be mediated through the generation of hydroxyl radicals which can be formed by the interaction of superoxide anion (from LY83583) and NO (from SNP), and that intracellular Ca2+ release from internal stores may play an important role in the cytotoxic mechanism of hydroxyl radicals.
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PMID:Mechanism of potentiation of LY83583-induced growth inhibition by sodium nitroprusside in human brain tumor cells. 762 54


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