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)

Sodium nitroprusside (SNP) stimulates cGMP formation to a greater extent in 20,000 g supernatant fractions of the human neuroblastoma clones NB1-G and SH-SY5Y than in the human astrocytoma clone D384. This suggests that these cell lines contain the soluble form of guanylate cyclase. Arachidonic, 8,11,14- and 11,14,17-eicosatrienoic acids inhibit SNP (10(-4) M)-stimulated cGMP formation more potently than the C18 unsaturated fatty acids linolenic and linoleic acids in D384 and NB1-G. In contrast the C20 saturated fatty acid, arachidic acid had little effect even at 10(-4) M concentration. In addition arachidonic and 8,11,14-eicosatrienoic acids inhibited basal guanylate cyclase activity, in NB1-G, over the same concentration range as they inhibited SNP-stimulated cGMP formation. No evidence could be obtained for the stimulation of guanylate cyclase by arachidonic acid in either NB1-G or D384. These results provide further support for suggestions that arachidonic acid or its metabolites may be important regulators of cGMP formation in the nervous system.
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PMID:The effect of unsaturated fatty acids on sodium nitroprusside stimulation of guanylate cyclase in the human astrocytoma clone, D384, and the human neuroblastoma clone, NB1-G. 196 40

The rates of phosphodiesterase-promoted hydrolysis of cGMP and cAMP have been measured in intact neuroblastoma N1E-115 cells by determining rates of 18O incorporation from 18O-water into the alpha-phosphoryls of guanine and adenine nucleotides. The basal rate of guanine nucleotide alpha-phosphoryl labeling ranged from 180 to 244 pmol X mg protein-1 X min-1. Sodium nitroprusside (SNP) caused a sustained 3.4-fold increase in this 18O-labeling rate in conjunction with 28- and 50-fold increases in cellular cGMP concentration at 3 and 6 min, respectively. This 18O-labeling rate (795 pmol X mg protein-1 X min-1) corresponded with the sum of the low (1.7 microM) and high (34 microM) Km phosphodiesterase activities assayable in cell lysates which exhibited a combined maximum velocity of 808 pmol X mg protein-1 X min-1 to which the high Km species contributed 84%. This information and the characteristics of the profile of 18O-labeled molecular species indicate that cGMP metabolism was restricted to a very discrete cellular compartment(s) of approximately 12% of the cell volume. Carbachol (1 mM) produced a transient increase (6-fold) in cellular cGMP concentration and a transient increase (90%) in the rate of 18O labeling of alpha-GTP during the first minute of treatment which translates into 30 additional cellular pools of cGMP hydrolyzed in this period. IBMX (1 mM) produced a relatively rapid increase in cellular cGMP (3- to 5-fold) and cAMP (2-fold) concentrations and a delayed inhibition of 18O labeling of guanine and adenine nucleotide alpha-phosphoryls without further elevation of cyclic nucleotide levels. These results indicate that besides inhibiting cyclic nucleotide hydrolysis, IBMX also imparts a time-dependent inhibitory influence on the generation of cyclic nucleotides. The data obtained show that measurement of 18O labeling of guanine and adenine nucleotide alpha-phosphoryls combined with measurements of cyclic nucleotide steady state levels provides a means to assess the rates of cyclic nucleotide synthesis and hydrolysis within intact cells and to identify the site(s) of action of agents that alter cellular cyclic nucleotide metabolism.
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PMID:The dynamics of cGMP metabolism in neuroblastoma N1E-115 cells determined by 18O labeling of guanine nucleotide alpha-phosphoryls. 243 34

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

Defective tissue perfusion and nitric oxide production and altered myo-inositol metabolism and protein kinase C activation have been invoked in the pathogenesis of diabetic complications including neuropathy. The precise cellular compartmentalization and mechanistic interrelationships of these abnormalities remain obscure, and nitric oxide possesses both neurotransmitter and vasodilator activity. Therefore the effects of ambient glucose and myo-inositol on nitric oxide-dependent cGMP production and protein kinase C activity were studied in SH-SY5Y human neuroblastoma cells, a cell culture model for peripheral cholinergic neurons. D-Glucose lowered cellular myo-inositol content, phosphatidylinositol synthesis, and phosphorylation of an endogenous protein kinase C substrate, and specifically reduced nitric oxide-dependent cGMP production a time- and dose-dependent manner with an apparent IC50 of approximately 30 mM. The near maximal decrease in cGMP induced by 50 mM D-glucose was corrected by the addition of protein kinase C agonists or 500 microM myo-inositol to the culture medium, and was reproduced by protein kinase C inhibition or downregulation, or by myo-inositol deficient medium. Sodium nitroprusside increased cGMP in a dose-dependent fashion, with low concentrations (1 microM) counteracting the effects of 50 mM D-glucose or protein kinase C inhibition. The demonstration that elevated D-glucose diminishes basal nitric oxide-dependent cGMP production by myo-inositol depletion and protein kinase C inhibition in peripheral cholinergic neurons provides a potential metabolic basis for impaired nitric oxide production, nerve blood flow, and nerve impulse conduction in diabetes.
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PMID:Modulation of basal nitric oxide-dependent cyclic-GMP production by ambient glucose, myo-inositol, and protein kinase C in SH-SY5Y human neuroblastoma cells. 860 30

Sodium nitroprusside is widely used in pharmacological studies as a potent vasodilator or a nitric oxide donor. The mechanisms of cellular death induced by sodium nitroprusside were investigated in murine neuroblastoma N1E-115 cells. Sodium nitroprusside reduced the cellular viability, and the DNA extracted from treated cells showed a ladder-like intranucleosomal fragmentation pattern, which is an indication of apoptosis. The DNA fragmentations were also visualized by in situ nick translation. The cellular death was attenuated by cycloheximide, indicating that ongoing protein synthesis was essential for the initiation of the degenerative response. However, other nitric oxide donors did not decrease the cellular viability. The nitric oxide scavenger, hemoglobin, had no effect on sodium nitroprusside-induced cellular death. Furthermore, sodium cyanide, which is formed by the metabolism of sodium nitroprusside, did not cause cellular death. On the other hand, hydrogen peroxide, another product of sodium nitroprusside metabolism, reduced the cellular viability and induced DNA fragmentation. In addition, the cell damage induced by sodium nitroprusside was enhanced by a medium without fetal bovine serum. In conclusion, we proposed that hydrogen peroxide is the important toxic species for induction of apoptosis in N1E-115 cells exposed to sodium nitroprusside.
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PMID:Sodium nitroprusside-induced apoptotic cellular death via production of hydrogen peroxide in murine neuroblastoma N1E-115 cells. 864 75

Nitric oxide is a chemical messenger implicated in neuronal damage associated with ischemia, neurodegenerative disease, and excitotoxicity. Excitotoxic injury leads to increased NO formation, as well as stimulation of the p38 mitogen-activated protein (MAP) kinase in neurons. In the present study, we determined if NO-induced cell death in neurons was dependent on p38 MAP kinase activity. Sodium nitroprusside (SNP), an NO donor, elevated caspase activity and induced death in human SH-SY5Y neuroblastoma cells and primary cultures of cortical neurons. Concomitant treatment with SB203580, a p38 MAP kinase inhibitor, diminished caspase induction and protected SH-SY5Y cells and primary cultures of cortical neurons from NO-induced cell death, whereas the caspase inhibitor zVAD-fmk did not provide significant protection. A role for p38 MAP kinase was further substantiated by the observation that SB203580 blocked translocation of the cell death activator, Bax, from the cytosol to the mitochondria after treatment with SNP. Moreover, expressing a constitutively active form of MKK3, a direct activator of p38 MAP kinase promoted Bax translocation and cell death in the absence of SNP. Bax-deficient cortical neurons were resistant to SNP, further demonstrating the necessity of Bax in this mode of cell death. These results demonstrate that p38 MAP kinase activity plays a critical role in NO-mediated cell death in neurons by stimulating Bax translocation to the mitochondria, thereby activating the cell death pathway.
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PMID:p38 MAP kinase mediates bax translocation in nitric oxide-induced apoptosis in neurons. 1090 76

CHP212 neuroblastoma cells were exposed to two different nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside. Apoptosis and necrosis were determined with flow cytometric analysis of annexin V binding and propodium iodide uptake. Both S-nitroso-N-acetylpenicillamine and sodium nitroprusside induced apoptosis, but with a different time dependency. Oxyhemoglobin (NO scavenger) attenuated the toxicity of S-nitroso-N-acetylpenicillamine, but had no effect on the toxicity of sodium nitroprusside. By contrast, deferoxamine (iron chelator) attenuated the toxicity of sodium nitroprusside, but had no effect on the toxicity of S-nitroso-N-acetylpenicillamine. Urate (ONOO(-) scavenger) did not influence the toxicity of either S-nitroso-N-acetylpenicillamine or sodium nitroprusside, but protected from SIN-1 (3-morpholinosydnonimine, ONOO(-) donor). It was shown that both dithiothreitol and ascorbic acid affected the toxicity of S-nitroso-N-acetylpenicillamine and sodium nitroprusside in opposite ways. In the presence of dithiothreitol, superoxide dismutase and catalase decreased the toxicity of sodium nitroprusside. In the presence of cells, but not in their absence, S-nitroso-N-acetylpenicillamine decomposed with a half-life of about 4 h as assessed by the production of nitrite and absorbance reduction at 335 nm. Sodium nitroprusside decomposed very slowly in the presence of cells as assessed by the production of ferrocyanide. It can be concluded that (1) slow and sustained release of NO from S-nitroso-N-acetylpenicillamine at the cell surface causes apoptosis in CHP212 cells, probably without the involvement of ONOO(-), (2) sodium nitroprusside causes apoptosis by the production of H(2)O(2) and/or iron, rather than NO, and probably has to be taken up by the cell for decomposition.
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PMID:S-nitroso-N-acetylpenicillamine and nitroprusside induce apoptosis in a neuronal cell line by the production of different reactive molecules. 1091 81

Nitric oxide (NO) is believed to play important roles in neuronal degeneration. In this study, the effects of NO on cell growth and apoptosis have been examined in human neuroblastoma cell line SK-N-SH. Sodium nitroprusside (SNP), a NO donor, was found to significantly inhibit cell growth and to induce apoptosis. The inhibitory and apoptotic activities of SNP followed a dose- and time-dependent manner. Ginkgolide A, B (GA, B), and huperzine A (Hup A), the three compounds isolated from Chinese herbs, blocked the inhibition of cell growth and apoptosis induced by SNP. The results suggest that inhibition of NO-induced neurotoxicity may be one mechanism of the above three therapeutic agents in neurodegenerative diseases.
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PMID:Ginkgolide A, B, and huperzine A inhibit nitric oxide-induced neurotoxicity. 1243 56

The work presented here verifies the hypothesis that RS-alpha-lipoic acid may exert its cholinoprotective and cholinotrophic activities through the maintenance of appropriate levels of acetyl-CoA in mitochondrial and cytoplasmic compartments of cholinergic neurons. Sodium nitroprusside (SNP) and amyloid-beta decreased pyruvate dehydrogenase, choline acetyltransferase activities, acetyl-CoA content in mitochondria and cytoplasm, as well as increased fraction of non-viable, trypan blue positive cells in cultured differentiated cholinergic SN56 neuroblastoma cells. Lipoic acid totally reversed toxin-evoked suppression of choline acetyltrasferase and pyruvate dehydrogenase activities, as well as mitochondrial and cytoplasmic acetyl-CoA levels, and partially attenuated increase of cell mortality. Significant negative correlations were found between enzyme activities, acetyl-CoA levels and cell mortality in different neurotoxic and neuroprotective conditions employed here. The level of cytoplamic acetyl-CoA correlated with mitochondrial acetyl-CoA, whereas choline acetyltransferase activity followed shifts in cytoplasmic acetyl-CoA. Thus, we conclude that, in cholinergic neurons, particular elements of the pyruvate-acetyl-CoA-acetylcholine pathway form a functional unit responding uniformly to nerotoxic and neuroprotectory conditions.
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PMID:RS-alpha-lipoic acid protects cholinergic cells against sodium nitroprusside and amyloid-beta neurotoxicity through restoration of acetyl-CoA level. 1678 7

Sodium nitroprusside (SNP) is a water-soluble iron nitrosyl complex clinically used as a powerful vasodilator for treatment of hypertension; and, in basic research, it has been used to mainly investigate the cytotoxic effects of nitrosative stress. Although NO is considered a pharmacologically active molecule, not all of the biological effects of SNP are dependent on its NO moiety. To elucidate the molecular executioner(s) responsible for SNP cytotoxicity, this study determines the involvement of oxidative stress in p53 activation and apoptotic induction elicited by SNP in SH-SY5Y neuroblastoma cells. We demonstrate that proapoptotic activity of SNP is independent of NO production, because SNP and its 2-day light-exhausted compound SNP(ex) trigger apoptosis to the same extent. We provide evidence for the occurrence of oxidative stress and oxidative damage during both SNP and SNP(ex) exposure and demonstrate that iron-derived reactive oxygen species (ROS) are the genuine mediators of their cytotoxicity. We show that p53 is equally activated upon both SNP and SNP(ex) treatments. Moreover, as demonstrated by small interfering RNA experiments, we indicate its primary role in the induction of apoptosis, suggesting the ineffectiveness of NO in its engagement. The attenuation of p53 levels, obtained by oxy-radical scavengers, is consistent with the recovery of cell viability and ROS decrease, demonstrate that SNP-mediated p53 activation is an event triggered by ROS and/or ROS-mediated damages. Together, our results suggest that investigations of the physiopathological effects of SNP should consider the role of ROS, other than NO, particularly in some conditions such as apoptotic induction and p53 activation.
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PMID:Reactive oxygen species mediate p53 activation and apoptosis induced by sodium nitroprusside in SH-SY5Y cells. 1867 76


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