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)

Polychlorinated biphenyls (PCBs) are widespread persistent environmental pollutants. Chronic human and animal exposure to PCBs results in various harmful effects including neurotoxicity. This study investigates the effects of the PCB mixture Aroclor 1254 (A1254) and two PCB congeners (coplanar, non-ortho PCB 126, and non coplanar PCB 99) on the expression of N-methyl-D-aspartate receptors (NMDARs) and the subsequent toxic effects using a human SHS5-SY neuroblastoma cell line. NMDAR was measured using a radiolabeled phencyclidine receptor ligand [(3)H]-MK801, apoptosis was quantified using fluorogenic substrates specific for caspase-3 (DEVD-AFC) and cell death using lactate dehydrogenase (LDH) release. After treatment, a positive dose-response relationship of increasing NMDARS, increasing caspase-3 activity and cell death was observed in all PCB compounds. The non-coplanar PCB compounds were found to be significantly more toxic than the coplanar congener and the PCB mixture A1254. PCB-mediated cell death was attenuated with 10microM NMDAR antagonists: 1-amino-3,5-dimethyladamantane hydrochloride (memantine) and (+)-5-methyl-10,11-dihydro-5H-debenzocyclhepten-5,10-imine maleate ((+)-MK-801), thus demonstrating the importance of NMDAR in PCB neurotoxicity. Intracellular calcium [Ca(2+)](i) chelator BAPTA-AM (1microM) partially attenuated the neurotoxic effect of the PCBs suggesting a role of calcium homeostasis disruption in the neurotoxicity of PCBs. These results suggest that the neurotoxicity of PCBs can be mediated through activation of NMDARs.
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PMID:Role of N-methyl-D-aspartate receptors in polychlorinated biphenyl mediated neurotoxicity. 1902 67

Previously, we found that neurosteroids inhibited hydrogen peroxide- and staurosporine-induced damage of undifferentiated human neuroblastoma SH-SY5Y cells. However, differentiated neuroblastoma cells morphologically and functionally resemble neuronal cells, and are thus considered to be a model system for studying neuronal apoptotic processes. In the present study, we examined the effects of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and pregnenolone (PGL) on the viability of retinoic acid-differentiated human neuroblastoma SH-SY5Y cells. Mitochondrial and extracellular apoptotic processes in these cells were induced by staurosporine and doxorubicin, respectively. Calcein viability assays showed that doxorubicin (0.5 microM for 24 h) decreased cell viability by ca. 20% as compared to control cultures. DHEA and DHEAS at 0.1 and 1 microM concentrations, respectively, significantly inhibited the doxorubicin toxicity. PGL showed a neuroprotective effect only at 0.1 microM, whereas it was inactive at a higher concentration (1 microM). Staurosporine (1 microM for 24 h) decreased SH-SY5Y cell viability by ca. 50%. DHEA (0.1 and 1 microM) and DHEAS (0.1 and 1 microM) significantly antagonized the toxic effects of staurosporine, whereas these compounds showed no activity at the lowest concentration (0.01 microM). PGL inhibited the staurosporine-induced decrease in cell viability only at the concentration of 0.1 microM. Since staurosporine generated a stronger detrimental effect on SH-SY5Y cell viability than doxorubicin, we studied the mechanisms of neurosteroid action only in the former model. Staurosporine (1 microM for 24 h) enhanced lactate dehydrogenase (LDH) release by ca. 40% and this effect was inhibited by DHEA (0.01, 0.1, and 1 microM), DHEAS (0.1 and 1 microM) and PGL (0.01 and 01 microM). In order to verify an involvement of phosphatidylinositol-3-kinase (PI3-K) in the antiapoptotic action of neurosteroids, a specific inhibitor of this protein kinase (LY294002 at 10 microM) was used. Pretreatment of the cells with LY294002 antagonized the ameliorating effects of DHEA, DHEAS, and PGL on staurosporine-induced LDH release. These data indicated that at physiological concentrations, DHEA, DHEAS, and PGL prevented RA-differentiated SH-SY5Y cell damage produced by activation of both mitochondrial and extracellular apoptotic pathways. Furthermore, this study confirmed that the neuroprotective effects of neurosteroids in a staurosporine model of cytotoxicity appeared to be dependent upon PI3-K activity.
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PMID:Neurosteroids enhance the viability of staurosporine and doxorubicin treated differentiated human neuroblastoma SH-SY5Y cells. 1906 15

Acrolein, an unsaturated aldehydic product of lipid peroxidation, has been implicated in the pathogenesis of various neurodegenerative disorders including Parkinson's disease. However, protection against acrolein toxicity in neuronal cells via chemical upregulation of cellular aldehyde-detoxification factors has not been investigated. In this study, we have investigated the induction of glutathione (GSH), GSH S-transferase (GST), and aldose reductase (AR) by the unique nutraceutical compound 3H-1,2-dithiole-3-thione (D3T); and the protective effects of the D3T-mediated cellular defenses on acrolein-mediated toxicity in human neuroblastoma SH-SY5Y cells. Incubation of SH-SY5Y cells with D3T (10-100 microM) resulted in a marked concentration- and time-dependent induction of GSH, but not GST or AR. D3T treatment also led to increased mRNA expression of gamma-glutamylcysteine ligase (GCL), the key enzyme in GSH biosynthesis. Incubation of SH-SY5Y cells with 40 microM acrolein for 0.5 or 1 h resulted in a significant depletion of cellular GSH, which preceded the decrease of cell viability, suggesting critical involvement of GSH in acrolein-induced cytotoxicity. Pretreatment of SH-SY5Y cells with 100 microM D3T afforded a dramatic protection against acrolein-induced cytotoxicity, as assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) reduction, lactate dehydrogenase release, as well as morphological changes. To further demonstrate the involvement of GSH in protection against acrolein-induced cytotoxicity, buthionine sulfoximine (BSO) was used to inhibit cellular GSH biosynthesis. Depletion of cellular GSH by 25 microM BSO dramatically potentiated acrolein-induced cytotoxicity. Cotreatment of SH-SY5Y cells with BSO and D3T was found to prevent the D3T-mediated GSH induction and completely reverse the cytoprotective effects of D3T on acrolein-induced toxicity. Taken together, this study demonstrates that upregulation of GSH is a predominant mechanism underlying D3T-mediated protection against acrolein-induced neurocytotoxicity.
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PMID:Upregulation of cellular glutathione by 3H-1,2-dithiole-3-thione as a possible treatment strategy for protecting against acrolein-induced neurocytotoxicity. 1907 13

The ability of galantamine (Reminyl) to inhibit the aggregation and toxicity of the beta-amyloid peptide (Abeta) was investigated. Galantamine showed concentration-dependent inhibition of aggregation of both Abeta 1-40 and Abeta 1-42, as determined by an ELISA method. Electron microscope studies of Abeta 1-40 incubated in the presence of galantamine revealed fibrils that were disordered and clumped in appearance. MTT and lactate dehydrogenase assays, employing SH-SY5Y human neuroblastoma cells, showed that galantamine reduced the cytotoxicity induced by Abeta 1-40. Galantamine also dramatically reduced Abeta 1-40-induced cellular apoptosis in these cells. There is some evidence that galantamine may not be acting purely as a symptomatic treatment. Disease-modifying effects of the drug could be due to an additional effect on Abeta aggregation and/or toxicity.
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PMID:Galantamine inhibits beta-amyloid aggregation and cytotoxicity. 1924 60

Mycotoxins are commonly encountered natural products, and are capable of poisoning animals or humans that inhale mold particles from mycotoxin-contaminated foods. Ochratoxin A (OTA) is produced by Aspergillu ochracus and Penicillium verrucosum, and is often found in cereals and agricultural products. Although previous studies have focused on the potent nephrotoxicity and renal carcinogenicity of OTA, more recent studies suggest that it accumulates in the brain and causes oxidative stress and DNA damage in various brain regions and neuronal populations. In the present study, we undertook to investigate the potential harm caused by environmental exposure to OTA in terms of its effects on neuronal cell viability and proteome profiles. OTA was found to significantly reduce the viabilities of human neuroblastoma SH-SY5Y and mouse hippocampal HT22 cells, as assessed by lactic dehydrogenase release into culture media. Generation of reactive oxygen species was detected in OTA-treated SH-SY5Y and HT22 cells, however, caspase activation and increase in p53 phosphorylation were only detected in HT22 cells, and the expressions of several proteins were found to be significantly altered after treating HT22 cells with OTA. Valosin containing protein, prolyl 4-hydroxylase, Atp5b protein, nucleophosmin 1, eukaryotic translation elongation factor 1 delta isoform, ornithine aminotransferase, prohibitin, and peroxiredoxin 6, which have been suggested to be implicated in the pathogenesis of neurodegenerative disorders, were up-regulated. Our findings suggest that coordinated regulations of molecular networks are involved in the OTA-induced cytotoxicity and that proteome response can be an indicative for neurodegeneration.
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PMID:Proteome response to ochratoxin A-induced apoptotic cell death in mouse hippocampal HT22 cells. 1944 61

Neuroblastomas originating from different sites might have different clinical and biological characteristics. In the present study, the clinical (age, sex and stage) and biological (N-myc amplification, Shimada pathology and levels of lactate dehydrogenase, ferritin and neuron-specific enolase) characteristics of patients with newly diagnosed neuroblastoma were compared according to the site of tumor origin (extra-abdominal versus abdominal). The event-free survival rate (EFS) was also compared between the two groups. Among 143 neuroblastomas, 115 tumors originated from the abdomen, 26 from extra-abdominal sites and 2 from unknown primary sites. Frequencies of stage 4 tumor and N-myc amplified tumor were lower in the extra-abdominal group than in the abdominal group (34.6% vs. 60.0%, P=0.019 and 4.2% vs. 45.0%, P<0.001, respectively). Levels of lactate dehydrogenase, ferritin and neuron-specific enolase were significantly lower in the extra-abdominal group than in the abdominal group. The probability of 5-yr EFS (+/-95% confidence interval) was higher in the extra-abdominal group than in the abdominal group (94.4+/-10.6% vs. 69.4+/-9.4%, P=0.026). Taken together, neuroblastomas originating from extra-abdominal sites might be associated with more favorable clinical and biological characteristics and a better outcome than neuroblastomas originating from abdomen.
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PMID:Neuroblastoma originating from extra-abdominal sites: association with favorable clinical and biological features. 1954 10

The Italian Neuroblastoma Registry was investigated to describe 781 children with neuroblastoma experiencing tumour recurrence (424 progressions and 357 relapses). Ten-year overall survival (OS) was 6.8% (95% confidence interval (CI) 4.3-10.0) after progression and 14.4% (95% CI 10.5-18.9) after relapse. For both circumstances, OS was better for age at diagnosis <18 months, less advanced International Neuroblastoma Staging System (INSS) stage, normal lactate dehydrogenase (LDH) serum level, normal MYCN gene status (P<0.001) and a non-abdominal primary site (P=0.034 for progression, and P=0.004 for relapses). A local type of recurrence had a significantly better outcome only in case of relapse (P<0.001). Probability of survival increased by era of diagnosis. Survival of children with recurrent neuroblastoma is very poor. A small cohort of patients, mainly represented by children with stages 1 and 2 who underwent local recurrence or developed late relapse may still benefit from further conventional treatment. For the remaining larger proportion of patients, experimental therapies should be proposed.
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PMID:Outcome of children with neuroblastoma after progression or relapse. A retrospective study of the Italian neuroblastoma registry. 1961 26

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

Oestrogens are powerful endogenous and exogenous neuroprotective hormones in animal models of brain injury, including focal cerebral ischaemia. This protective effect has been demonstrated under a variety of different treatments and injury paradigms, such as in vivo and in vitro stroke conditions. Neuroprotection in the central nervous system by progesterone is less defined. In the present study, cultured cortical and midbrain mouse neurones and human neuroblastoma cells (SH-SY5Y) were exposed to combined glucose-serum deprivation (CGSD), which is regarded as a reliable model mimicking the effects of ischaemia in vitro. Cell viability was assayed using lactate dehydrogenase release and metabolic activity. Conditions for CGSD treatment were chosen to yield half-maximal cell death rates. The validity of CGSD in vitro was compared with permanent middle cerebral artery occlusion (MCAO) in vivo. CGSD for 4 h induced half-maximal neuronal cell death. MCAO in vivo for the same period resulted in significant neuronal loss, also suggesting the validity of CGSD as a suitable stroke-like in vitro model. Combined steroid treatment (17beta-oestradiol and progesterone) but not the application of single steroids abolished CGSD-induced cell death of cortical neurones in vitro. By contrast, no cell protection was found in midbrain neurones or neuroblastoma cells. The co-application of oestrogen (ICI 182,780) or progesterone (RU-486) receptor antagonists did not obviously counteract the protective steroid effects. This suggests the operation of nonclassical steroid mechanisms and their implication in mediation of hormonal effects. The surplus of combined protective hormonal effects might be a result of the observed influence of progesterone application on neuronal oestradiol synthesis. The data obtained in the present study clearly highlight the potential of a combined steroid treatment under toxic degenerative brain pathologies.
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PMID:Combined 17beta-oestradiol and progesterone treatment prevents neuronal cell injury in cortical but not midbrain neurones or neuroblastoma cells. 1968 48

Regular consumption of green tea benefits people in prevention from cardiovascular disorders, obesity as well as neurodegenerative diseases. (-)-Epigallocatechin-3-gallate (EGCG) is regarded as the most biologically active catechin in green tea. However, the stability and bioavailability of EGCG are restricted. The purpose of the present study was to investigate whether a pro-drug, a fully acetylated EGCG (pEGCG), could be more effective in neuroprotection in Parkinsonism mimic cellular model. Retinoic acid (RA)-differentiated neuroblastoma SH-SY5Y cells were pre-treated with different concentrations of EGCG and pEGCG for 30 min and followed by incubation of 25 microM 6-hydroxydopamine (6-OHDA) for 24h. We found that a broad dosage range of pEGCG (from 0.1 to 10 microM) could significantly reduce lactate dehydrogenase release. Likewise, 10 microM of pEGCG was effective in reducing caspase-3 activity, while EGCG at all concentrations tested in the model failed to attenuate caspase-3 activity induced by 6-OHDA. Furthermore, Western-blot analysis showed that Akt could be one of the specific signaling pathways stimulated by pEGCG in neuroprotection. It was demonstrated that 25 microM of 6-OHDA significantly suppressed the phosphorylation level of Akt. Only pEGCG at 10 microM markedly increased its phosphorylation level compared to 6-OHDA alone. Taken together, as pEGCG has higher stability and bioavailability for further investigation, it could be a potential neuroprotective agent and our current findings may offer certain clues for optimizing its application in future.
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PMID:A pro-drug of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine. 2002 75


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