Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Human neuroblastoma CHP100 cells were forced into apoptosis (programmed cell death, PCD) or necrosis by treatment with calcium chloride or sodium nitroprusside (a nitric oxide donor), respectively. Cellular luminescence, a marker of membrane lipid peroxidation, was increased by calcium but not by nitroprusside, and reached a maximum of 4-fold the control value 2 hours after treatment. The increase in luminescence was paralleled by increased 5-lipoxygenase (up to 250% of the control value) and decreased catalase (down to 50%) activity within the same time window. Consistently, incubation of CHP100 cells with inhibitors of 5-lipoxygenase (5,8,11,14-eicosatetraynoic acid and MK886) reduced light emission and PCD, whereas inhibition of catalase by 3-amino-1, 2,4-triazole enhanced both processes. Treatment of CHP100 cells with retinoic acid or cisplatin, unrelated PCD inducers reported to activate the lipoxygenase pathway, also gave enhanced light emission parallel to PCD increase. Altogether, these results suggest that cellular luminescence is an early marker of apoptotic, but not necrotic, program(s) involving generation of hydrogen peroxide and activation of 5-lipoxygenase.
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PMID:The early phase of apoptosis in human neuroblastoma CHP100 cells is characterized by lipoxygenase-dependent ultraweak light emission. 1060 Apr 93

Isoniazid (INH) is one of the anti-tuberculosis drugs widely prescribed for patients since the early 1950s. It is relatively nontoxic but some patients develop peripheral neuropathy attributed to a disturbance of vitamin B6 metabolism. Some isoniazid metabolites are hepatotoxic but little is known about their neurotoxic property. Isoniazid and its metabolites including acetylisoniazid, acetylhydrazine, diacetylhydrazine, isonicotinic acid and hydrazine were examined for their potential neurotoxic effects in cultured mouse dorsal root ganglion (DRG) neurons and mouse neuroblastoma x DRG neuron hybrid cell line N18D3. Isoniazid did not cause neurotoxicity at exposures up to 7 days. Hydrazine was found to be the most toxic metabolite with LC50 values of 2.7 mM and 0.3 mM after 7 days of exposure in DRG neurons and N18D3 hybrid neurons, respectively. Other metabolites including acetylisoniazid, acetylhydrazine, diacetylhydrazine and isonicotinic acid had moderate to minor neurotoxic effects on N18D3 hybrid neurons. Pyridoxine, which is used in clinical practice to prevent or ameliorate the isoniazid-induced neuropathy, did not consistently reverse the neurotoxicity of any of the metabolites in the cell cultures, but some interaction with hydrazine cannot be ruled out. Pyridoxine itself was found to be neurotoxic both in DRG neurons and N18D3 hybrid neurons, in agreement with human peripheral sensory neuropathy caused by prolonged overdosage. The enzymes catalase and superoxide dismutase and the antioxidant agent selenium showed some protection against hydrazine neurotoxicity, suggesting an involvement of the generation of reactive oxygen species in the pathogenesis of isoniazid neuropathy. Both mouse DRG neurons and N18D3 mouse hybrid neurons were shown to be useful culture systems for elucidating the neurotoxicity mechanisms of agents causing sensory neuropathies and general neurotoxic effects in the nervous system.
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PMID:Neurotoxicity of isoniazid and its metabolites in cultures of mouse dorsal root ganglion neurons and hybrid neuronal cell line. 1069 74

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

MPP(+), an active metabolite of MPTP, causes a dopaminergic neuronal degeneration similar to that observed in Parkinson's disease. Current data suggest that MPP(+)-induced cytotoxicity may be mediated by oxygen free radicals. To evaluate this hypothesis, we first investigated whether MPP(+) could cause oxidative stress by producing oxygen free radicals in the SH-SY5Y, human neuroblastoma cell line. MPP(+) was toxic to the cells dose-dependently but did not increase the level of lipid peroxidation at toxic concentrations. Second, we examined the effects of various antioxidants and an inhibitor of nitric oxide synthase (NOS) on the development of MPP(+) cytotoxicity. Pretreatment with antioxidants such as ascorbic acid, Trolox, phenyl-tertiary-butyl-nitrone (PBN), which show protective effects on tert-butyl hydroperoxide (tBOOH) toxicity did not attenuate MPP(+) cytotoxicity. Similarly, the combination of antioxidant enzymes, SOD and catalase (50 U/ml, respectively), did not protect the cells from the toxic action of MPP(+). Also N-nitro-l-arginine methyl ester (NAME), a competitive inhibitor of NOS, and combined incubation with NAME and antioxidant enzymes failed to attenuate MPP(+) cytotoxicity. On the other hand, a sublethal dose of MPP(+) potentiated iron and H(2)O(2)-induced cytotoxicity. These results suggest that oxygen free radicals may not be a primary cause of MPP(+)-induced cell death but that MPP(+) increases the vulnerability of cells to oxidative stress.
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PMID:MPP(+) increases the vulnerability to oxidative stress rather than directly mediating oxidative damage in human neuroblastoma cells. 1096 95

A potent inhibitor of type B monoamine oxidase, (-)deprenyl, is known to protect or rescue dying neurons, independent of inhibition of the enzyme activity. After long term administration to rodents, a propargylamine structurally related to (-)deprenyl, (R)(+)-N-propargyl-1-aminoindan (rasagiline) increased the activities of anti-oxidative enzymes, superoxide dismutase and catalase. Rasagiline protected in vitro dopamine cells from apoptosis induced by oxidative stress or neurotoxins. The mechanism of the anti-apoptotic effect was studied by in vitro experiments using human dopaminergic neuroblastoma, SH-SY5Y cells. Peroxynitrite-generating N-morpholino sydonimine (SIN-1) induced apoptosis in SH-SY5Y cells via disruption of mitochondrial membrane potential (DeltaPsim), followed by caspase 3 activation. Rasagiline prevented the loss of DeltaPsim, the initial step to apoptosis, and also following caspase 3-activation and DNA fragmentation. The results suggest that rasagiline may interact with the specific molecule in the mitochondria and suppress the death signal transduction. By the anti-apoptotic function, rasagiline may rescue or protect declining neurons in aging and neurodegenerative disorders, such as Parkinson's disease.
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PMID:Mechanism underlying anti-apoptotic activity of a (-)deprenyl-related propargylamine, rasagiline. 1099 18

The antioxidant responsive element (ARE) is a cis-acting regulatory element located in the 5'-flanking region of several genes encoding phase II detoxification enzymes, including NAD(P)H:quinone oxidoreductase (NQO1). We report here that activation of the NQO1 ARE by tert-butylhydroquinone (tBHQ) is dependent on Nrf2 and not oxidative stress in IMR-32 human neuroblastoma cells. Overexpression of wild-type Nrf2 activated ARE in a dose-dependent manner, and ARE activation by tBHQ or diethyl maleate (DEM) was inhibited by dominant/negative Nrf2 not by dominant/negative c-Jun. According to our observation, the palindromic sequence (5' to the core) and the GC box in the ARE core sequence are essential for maximal inducibility by tBHQ or DEM. Overexpression of Nrf2 selectively activated wild-type ARE up to 24 h. In addition, a dramatic nuclear translocation of Nrf2 by tBHQ supports a role for Nrf2 in ARE activation. Although oxidative stress is hypothesized to be a major driving force for ARE activation, pretreatment of antioxidant or antioxidant enzyme did not block tBHQ-mediated ARE activation. In contrast, ARE activation by DEM was inhibited by antioxidants or catalase. These results suggest that ARE activation signals from tBHQ and DEM converge at Nrf2 transcription factor through independent mechanisms.
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PMID:Nrf2-dependent activation of the antioxidant responsive element by tert-butylhydroquinone is independent of oxidative stress in IMR-32 human neuroblastoma cells. 1116 12

Peroxynitrite, one of the most reactive radicals, is produced from superoxide anion and nitric oxide. A peroxynitrite generator, 3-morpholinosydonimine (SIN-1), was found to induce the expression of three different growth arrest and DNA damage-inducible (GADD) mRNA, GADD34, GADD45, and GADD153, at the early phase during cell death in human neuroblastoma SH-SY5Y cells. In addition, peroxynitrite activated p38 MAPK just before induction of three GADD mRNA. A specific inhibitor of p38 MAPK, SB202190, markedly suppressed peroxynitrite-induced expression of three GADD mRNA in SH-SY5Y cells. The expression of three GADD genes and also p38 MAPK phosphorylation were suppressed by treatment with radical scavengers, superoxide dismutase plus catalase and glutathione. Glutathione depletion by L-buthionine-S, R-sulfoximine (BSO), increased the vulnerability of the cells to peroxynitrite. These findings indicate that peroxynitrite-mediated oxidative stress activated p38 MAPK to induce three GADD genes.
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PMID:Peroxynitrite induces GADD34, 45, and 153 VIA p38 MAPK in human neuroblastoma SH-SY5Y cells. 1116 39

The role of antioxidants in the neurotoxicity of the antimalarial endoperoxides artemether and dihydroartemisinin was studied in vitro by quantitative image analysis of neurite outgrowth in the neuroblastoma cell line NB2a. Intracellular glutathione concentrations were measured by high performance liquid chromatography with fluorescence detection. Both dihydroartemisinin (1 microM) and a combination of artemether (0.3 microM) plus haemin (2 microM) significantly inhibited neurite outgrowth from differentiating NB2a cells to 11.5 +/- 11.0% (SD) and 19.6 +/- 15.2% of controls, respectively. The inhibition by artemether/haemin was prevented by the antioxidants superoxide dismutase (109.7 +/- 47.8% of control), catalase (107.0 +/- 29.3%) glutathione (123.8 +/- 12.4%), L-cysteine (88.0 +/- 6.3%), N-acetyl-L-cysteine (107.8 +/- 14.9%), and ascorbic acid (104.3 +/- 12.7%). Dihydroartemisinin-induced neurotoxicity was completely or partially prevented by L-cysteine (99.5 +/- 17.7% of control), glutathione (57.9 +/- 23.4% of control), and N-acetyl-L-cysteine (57.3 +/- 9.5%), but was not prevented by superoxide dismutase, catalase, or ascorbic acid. Buthionine sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase, significantly increased the neurotoxic effect of non-toxic concentrations of artemether/haemin (0.1 microM/2 microM) and dihydroartemisinin (0.2 microM), suggesting that endogenous glutathione participates in the prevention of the neurotoxicity of artemether/haemin and dihydroartemisinin. Artemether/haemin completely depleted intracellular glutathione levels, whereas dihydroartemisinin had no effect. We conclude that although glutathione status is an important determinant in the neurotoxicity of endoperoxides, depletion of glutathione is not a prerequisite for their toxicity. This is consistent with their mechanisms of toxicity being free radical-mediated damage to redox-sensitive proteins essential for neurite outgrowth, or alteration of a redox-sensitive signalling system which regulates neurite outgrowth.
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PMID:The role of glutathione in the neurotoxicity of artemisinin derivatives in vitro. 1122 74

Neurotoxic effects of methylmercury, were investigated in vitro in primary cultures of human neurons and astrocytes isolatedfrom human fetal brain and in the human neuroblastoma cell line SH-SY5Y. The protection provided by agents with antioxidant properties was tested in these cultures to examine the oxidative stress mechanism of methylmercury poisoning. After 24 h of exposure to methylmercury, LC50 values were 6.5, 8.1 and 6.9 microM for human neurons, astrocytes and neuroblastoma cells, respectively, and the degree of cell damage increased at longer exposure times. Depletion of the cellular pool of reduced glutathione (GSH) by treatment with buthionine sulfoximine potentiated methylmercury cytotoxicity in all three cell types; neuroblastoma cells were the most sensitive. Addition of GSH extracellularly blocked methylmercury neurotoxicity in all cell types. The major beneficial effect of GSH could be attributed to its capacity to form conjugates with methylmercury, which reduces the availability of these organometallic molecules to the cells and facilitates their efflux. Cysteine protected astrocytes and neuroblastoma cells from methylmercury neurotoxicity, while selenite, Vitamin E and catalase produced some minor protective effects in three cell types, particularly in neurons. The present study showed that the human neural cells tested had differential responses to methylmercury: astrocytes were resistant to methylmercury neurotoxicity and neurons were more most responsive to protection afforded by antioxidants among the three cell types.
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PMID:Methylmercury neurotoxicity in cultures of human neurons, astrocytes, neuroblastoma cells. 1145 33

The reaction of proteins with reducing sugars leads to the formation of 'advanced glycation endproducts' (AGEs). They accumulate in Alzheimer's disease brain in the vicinity of beta-amyloid plaques. AGEs are cytotoxic by a mechanism involving reactive oxygen species, which implies that they could compromise glutathione redox status. In this study, we show that AGEs (BSA-AGE and beta-amyloid-AGE) persistently increase the ratio of oxidized to reduced glutathione in a dose- and time-dependent manner in SH-SY5Y neuroblastoma cells. The level of oxidized glutathione accounted to 10-14% and persisted for up to 24 h in the presence of added AGEs. In contrast, the unmodified beta-amyloid peptides A beta (1-40) and A beta (25-35) had no significant effect on glutathione redox status. The AGE-induced increase in oxidized glutathione could be prevented by the radical scavengers N-acetylcysteine, alpha-lipoic acid and 17beta-estradiol or by application of catalase, indicating that superoxide and hydrogen peroxide production precedes the AGE-mediated depletion of reduced glutathione.
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PMID:Advanced glycation endproducts change glutathione redox status in SH-SY5Y human neuroblastoma cells by a hydrogen peroxide dependent mechanism. 1157 38


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