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)

Glutathione (GSH) depletion is widely used to sensitize cells to anticancer treatment inducing the progression of programmed cell death and overcoming chemoresistance. It has been reported that neuroblastoma cells with MYCN amplification are unable to start TRAIL-dependent death and MYCN, in concert with cytotoxic drugs, efficiently induces the mitochondrial pathway of apoptosis through oxidative mechanisms. In this study, we show that GSH loss induced by L-buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH biosynthesis, leads to overproduction of reactive oxygen species (ROS) and triggers apoptosis of MYCN-amplified neuroblastoma cells. BSO susceptibility of SK-N-BE-2C, a representative example of MYCN-amplified cells, has been attributed to stimulation of total SOD activity in the absence of changes in the level and the activity of catalase. Therefore, the unbalanced intracellular redox milieu has been demonstrated to be critical for the progression of neuroblastoma cell death that was efficiently prevented by antioxidants and rottlerin. These results describe a novel pathway of apoptosis dependent on ROS formation and PKC-delta activation and independent of p53, bcl-2, and bax levels; the selective redox modulation of PKC-delta might be suggested as a potential strategy for sensitizing MYCN-amplified cells to therapeutic approaches.
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PMID:Mechanisms of BSO (L-buthionine-S,R-sulfoximine)-induced cytotoxic effects in neuroblastoma. 1799 46

The multifunctional, anti-Alzheimer drug, ladostigil (TV3326) [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate] combines the neuroprotective effects of the anti-Parkinson drug, rasagiline, a selective monoamine oxidase (MAO)-B inhibitor, with the cholinesterase (ChE) inhibitory activity of rivastigmine in a single molecule. Ladostigil has been shown to possess potent antiapoptotic and neuroprotective activities in various oxidative insults in vitro and in vivo, such as prevention of the fall in mitochondrial membrane potential and regulation of Bcl-2 family proteins. In the present study, we demonstrate that ladostigil (1 microM) increased cell viability, associated with the increase of catalase activity and decrease of intracellular reactive oxygen species (ROS) production in human SH-SY5Y neuroblastoma cells exposed to (hydrogen peroxide) H(2)O(2). Furthermore, ladostigil significantly elevated mRNA levels of the antioxidants enzymes, catalase, NAD(P)H quinone oxidoreductase 1 (NQO1) and peroxiredoxin 1 (Prx 1) in H(2)O(2)-treated SH-SY5Y cells. Chronic treatment with ladostigil (1 mg/kg gavage per day for 30 days) markedly up-regulated mRNA expression levels of various antioxidant enzymes in aged rat hippocampus (e.g. glutathione peroxidase precursor (GSHPX-P), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD)). These findings indicate that in addition to its multiple neuroprotective characteristics, ladostigil also possesses antioxidant properties, which might be beneficial for the treatment of oxidative stress (OS) in aging and age-associated neurodegenerative diseases.
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PMID:The neuroprotective effect of ladostigil against hydrogen peroxide-mediated cytotoxicity. 1859 87

The current therapeutic advance in which future drugs are designed to possess varied pharmacological properties and act on multiple targets has stimulated the development of the multimodal drug, ladostigil (TV3326; (N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate). Ladostigil combines neuroprotective effects with monoamine oxidase (MAO)-A and MAO-B and cholinesterase (ChE) inhibitory activities in a single molecule, as a potential treatment for Alzheimer's disease (AD) and Lewy body disease. In the present study, we demonstrate that ladostigil (10(-6)-10 muM) dose-dependently increased cell viability, associated with increased activity of catalase and glutathione reductase and decrease of intracellular reactive oxygen species production in a cytotoxic model of human SH-SY5Y neuroblastoma cells exposed to hydrogen peroxide (H(2)O(2)). In addition, ladostigil significantly upregulated mRNA levels of several antioxidant enzymes (catalase, NAD(P)H quinone oxidoreductase 1 and peroxiredoxin 1) in both H(2)O(2)-treated SH-SY5Y cells, as well as in the high-density human SK-N-SH neuroblastoma cultured apoptotic models. In vivo chronic treatment with ladostigil (1 mg/kg per os per day for 30 days) markedly upregulated mRNA expression levels of various enzymes involved in metabolism and oxidation processes in aged rat hippocampus. In addition to its unique combination of ChE and MAO enzyme inhibition, these results indicate that ladostigil displays neuroprotective activity against oxidative stress-induced cell apoptosis, which might be valuable for aging and age-associated neurodegenerative diseases.
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PMID:The novel cholinesterase-monoamine oxidase inhibitor and antioxidant, ladostigil, confers neuroprotection in neuroblastoma cells and aged rats. 1875 29

The microtubular network of neurons is involved in several functions such as formation and tropism of cellular processes, cell division and intracellular transport. A lot of evidences testify that the microtubular network of neurons can be impaired by oxidative stress. A condition of oxidative stress is often possible when D-glucose overloads its metabolic pathway, resulting in an increase in reactive oxygen species and subsequent neurological disorders. The aim of this work was to check in undifferentiated mouse neuroblastoma cells (C1300) the possible oxidative effects of D-glucose on microtubules. Using a concentration of 110mM D-glucose, cell morphology, growth rate, viability and catalase activity were seriously altered. Noteworthy, an increase in 3-nitro-L-tyrosine and a downregulation of tubulins was found in D-glucose-exposed cells, whereas another cytoskeletal proteins, namely actin, did not show any changes. In conclusion, microtubular network can be impaired by D-glucose through specific nitrosative effects, suggesting a possible mechanism at the basis of hyperglycemia-induced neuronal damage.
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PMID:D-glucose induces microtubular changes in C1300 neuroblastoma cell line through the incorporation of 3-nitro-L-tyrosine into tubulin. 1882 98

Antipsychotics are known to alter antioxidant activities in vivo. Therefore, the aim of the present study was to examine in the human neuroblastoma SH-SY5Y cell line the impact of a typical (haloperidol) and an atypical (quetiapine) antipsychotic on the expression of genes encoding the key enzymes of the antioxidant metabolism (Cu, Zn superoxide dismutase; Mn superoxide dismutase; glutathione peroxidase; catalase) and enzymes of the glutathione metabolism (gamma-glutamyl cysteine synthetase, glutathione-S-transferase, gamma-glutamyltranspeptidase, glutathione reductase). The cells were incubated for 24h with 0.3, 3, 30 and 300microM haloperidol and quetiapine, respectively; mRNA levels were measured by polymerase chain reaction. In the present study, we observed mostly significant decreases of mRNA contents. With respect to the key pathways, we detected mainly effects on the mRNA levels of the hydrogen peroxide detoxifying enzymes. Among the enzymes of the glutathione metabolism, glutathione-S-transferase- and gamma-glutamyltranspeptidase-mRNA levels showed the most prominent effects. Taken together, our results demonstrate a significantly reduced expression of genes encoding for antioxidant enzymes after treatment with the antipsychotics, haloperidol and quetiapine.
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PMID:Impact of haloperidol and quetiapine on the expression of genes encoding antioxidant enzymes in human neuroblastoma SH-SY5Y cells. 1910 87

The mechanisms of catechol-induced cytotoxicity were studied in cultures of neuroblastoma N2a cells. The minimal cytotoxic concentration after 72 h was 20 micromol x l(-1). The EC50 after 72 h was 38 micromol x l(-1). There was not a correlation between the cytotoxicity and the formation of quinones in the medium. Catechol-induced cytotoxicity was increased significantly when superoxide dismutase (SOD) was added. The addition of catalase did not protect cells, but this enzyme reverted the deleterious effect of SOD. The experimental studies showed a detrimental effect of deferoxamine on catechol-induced cytotoxicity suggesting that cells need iron to maintain its metabolism. NF-kappaB inhibitors increased the cytotoxicity, suggesting that this factor is also important for cell viability. L-cysteine and N-acetyl-L-cysteine protected cells significantly in a dose-dependent manner. The use of monochlorobimane showed that catechol induced reduced glutathione (GSH) depletion after 24 h, prior to cell death. The mode of cell death was studied by flow cytometry after double staining with annexin V and propidium iodide. Catechol induced apoptosis after 72 h. Furthermore, catechol also induced nuclear fragmentation. These data showed that catechol-induced cytotoxicity to N2a cell was not directly a consequence of reactive oxygen species production. Rather, it was due to GSH depletion followed by the induction of apoptosis.
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PMID:Cytotoxic effects of catechol to neuroblastoma N2a cells. 1920 5

Experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis, is characterized by demyelination, inflammation and neurodegeneration of CNS in which free radicals play a role. Recently, the efficacy of murine mesenchimal stem cells (MSCs) as treatment of EAE induced in mice by the encephalitogenic peptide MOG(35-55) was demonstrated. The present study analyzed some markers of oxidative stress, inflammation/degeneration and apoptosis such as metallothioneins (MTs), antioxidant enzymes (superoxide dismutase, catalase and glutathione-S-transferase), poly(ADP-ribose) polymerase-1 and p53 during EAE progression and following MSC treatment. Expression of the three brain MT isoforms increased significantly in EAE mice compared with healthy controls, but while expression of MT-1 and MT-3 increased along EAE course, MT-2 was up-regulated at the onset, but returned to levels similar to those of controls in chronic phase. The changes in the transcription and activity of the antioxidant enzymes and in expression of poly(ADP-ribose) polymerase-1 and p53 showed the same kinetics observed for MT-1 and MT-3 during EAE. Interestingly, i.v. administration of MSCs reduced the EAE-induced increases in levels/activities of all these proteins. These results support an antioxidant and neuroprotective activity for MSCs that was also confirmed in vitro on neuroblastoma cells exposed to an oxidative insult.
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PMID:Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo. 1961 33

Alzheimer's disease is the major cause of senile dementia with the hallmark of beta-amyloid deposition in neurons. Although the main cause(s) of this deposition is not fully understood, however, the wealth of the present literature data supports the pivotal role of reactive oxygen and nitrogen species in both the initiation and progression of beta-amyloid aggregation and deposition. In the present study, we were interested to evaluate the free-radical protecting effect of AA3E2, a triazine derivative with a beta-amyloid-breaking activity, among SK-N-MC neuroblastoma cells exposed to hydrogen peroxide (H(2)O(2)) as an exogenous source of free radicals. Exposure of the cells to different doses of AA3E2 (1-16 microM) for 3h followed by subsequent exposure to a single dose of H(2)O(2) (mainly 150 microM) attenuated the extent of superoxide dismutase (SOD) and catalase (CAT) inhibition by H(2)O(2), in a dose dependent manner. Furthermore, significant reduction was observed in the extent of cellular lactate dehydrogenase release, intracellular ROS and the extent of apoptosis among the cells pre-treated with AA3E2. Based on these data, an antioxidant mode of action is proposed for AA3E2 besides its previously beta-amyloid-breaking activity.
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PMID:Inhibition of H2O2-induced neuroblastoma cell cytotoxicity by a triazine derivative, AA3E2. 1961 24

The role of beta-amyloid (A beta) in the pathogenesis of Alzheimer's disease (AD) is frequently reported in the literature. Though the exact mode of action is not known, it is suggested that A beta induces cell death through induction of oxidative stress possibly through hydrogen peroxide generation. In that case, antioxidants should be capable of attenuating the A beta-induced cytotoxicities. In that regard, we evaluated the effect(s) of a triazine-derivative, AA3E2, with established antioxidant activity. Pretreatment of SK-N-MC neuroblastoma cells with AA3E2, followed by exposure to A beta(1-42) showed 28.3% higher viability relative to the control cells which has not been treated with AA3E2. In addition, AA3E2 inhibited caspase-3 activation caused by A beta(1-42) and it attenuated A beta(1-42)-induced intracellular ROS (reactive oxygen species) accumulation. The lower level of intracellular free radicals was further confirmed by higher and lower activities of intracellular catalase and superoxide dismutase, respectively. These observations, parallel to the literature data, reconfirm the oxidative stress disrupting role of A beta(1-42) peptide. Thus, sequestration of this role by potential antioxidants such as AA3E2 might happen to be a suitable strategy for future treatments of AD.
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PMID:Protective effect of a triazine-derivative (AA3E2) on beta-amyloid-induced damages in SK-N-MC cells. 1963 Dec 65

Oxidative stress has long been linked to cell death in many neurodegenerative conditions. Treatment with antioxidants is a promising approach for slowing disease progression. In this study, we used the neuroblastoma SH-SY5Y cells as an in vitro model to first assess the effect of polypeptide from Chlamys farreri (PCF), a natural marine antioxidant, on H(2)O(2)-induced neuronal cell death. Pre-treatment of SH-SY5Y cells with PCF inhibited H(2)O(2)-induced cell death in a concentration-dependent manner. In parallel, intracellular reactive oxygen species generation and lipid peroxidation were inhibited by PCF. Under severe H(2)O(2) insult, PCF promoted endogenous antioxidant defense components including glutathione peroxidase, catalase, superoxide dismutase, and glutathione. PCF also protected DNA from oxidative damage and enhanced the removal of 8-oxo-7,8-dihydro-2'-deoxyguanosine from DNA. Further, we found that PCF potentially prevented H(2)O(2)-induced cell apoptosis. When investigated mitogen-activated protein kinase signaling pathway, we found that pre-treatment of cells with PCF significantly blocked H(2)O(2)-induced phosphorylation of c-Jun N-terminal kinase of the mitogen-activated protein kinase family. However, PCF had little inhibitory effect on the H(2)O(2)-induced activation of extracellular signal-regulated kinase. Taken together, these data demonstrate that PCF prevents oxidative stress-induced reactive oxygen species production and c-Jun N-terminal kinase activation and may be useful in the treatment of neurodegenerative diseases.
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PMID:Cytoprotective effect of polypeptide from Chlamys farreri on neuroblastoma (SH-SY5Y) cells following HO exposure involves scavenging ROS and inhibition JNK phosphorylation. 1968 11


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