UMLS:C0027819 - FACTA Search

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Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, causes equine leukoencephalomalacia, impairs myelination, and inhibits neuronal growth in vitro. Intact mice do not show brain damage after systemic administration of FB1. We recently reported that intracerebroventricular administration of FB1 in mice caused neurodegeneration in the cortex and activation of astrocytes in the hippocampal area; results suggested that the neuronal damage may be secondary to activation of immunocompetent non-neuronal cells. Current study investigated effects of FB1 upon murine microglial (BV-2) and neuroblastoma (N2A) cell lines, and primary astrocytes and cortical neurons. BV-2 and N2A cultures and cells prepared from neonatal and postnatal brains of BALB/c mice were exposed to various concentrations of FB1 for 4 (BV-2 and N2A) or 4 and 8 (astrocytes and cortical neurons) days. FB1 at 25 microM decreased viability in BV-2 cells, whereas at 50 microM caused necrotic but not apoptotic cell death in both BV-2 and primary astrocytes (at day 8 only), assessed by lactic dehydrogenase release, and pripidium iodide and annexin V staining. Thymidine incorporation indicated that 2.5 microM FB1 decreased proliferation in BV-2 cells. DNA analysis by flow cytometry showed that the inhibition was not caused by cell cycle arrest. The mitochondrial activity decreased dose-dependently in BV-2 cells and was significantly elevated at 25 microM FB1, but not at 50 microM at days 4 or 8 in astrocytes. In BV-2 cells and primary astrocytes, the expression of TNFalpha and IL-1beta analyzed by real-time polymerase chain reaction was downregulated at 6 or 24 h. In all cell types tested the FB1 treatment caused accumulation of free sphinganine and decrease in free sphingosine levels at selected time points. Results indicated that primary and established murine brain immunocompetent cells are vulnerable to the FB1-dependent cytotoxicity in vitro whereas neuronal cells are not. The toxic effects on the neuronal tissue may therefore be secondary to modulation of astrocyte or glial cell function.
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PMID:Fumonisin B1 induces necrotic cell death in BV-2 cells and murine cultured astrocytes and is antiproliferative in BV-2 cells while N2A cells and primary cortical neurons are resistant. 1600 69

Using human neuroblastoma SH-SY5Y cells, effects of acrylamide on p53 protein and intracellular signal transducting pathways were examined. Acrylamide increased p53, phosphorylated p53, and p53-associated protein murine double minute 2 (MDM2). The phosphorylation of p53 was specific for the Ser15 site. Among mitogen-activated protein kinases (MAPKs), acrylamide caused phosphorylation of extracellular signal-regulated protein kinase (ERK) and p38 but not c-Jun NH(2)-terminal kinase. Nevertheless, blocking p38 pathway by LL-Z1640-2 did not suppress the phosphorylation of p53 at Ser15. In contrast, a specific inhibitor of ERK kinase (U0126 or PD98059) could abolish the accumulation as well as the phosphorylation of p53 at Ser15. Elevation of MDM2 was also abolished by U0126. An inhibitor of phosphatidylinositol 3-kinase-related kinase (PIKK) pathway (wortmannin) suppressed the increase of p53 and its phosphorylation at Ser15. Hence, acrylamide increases p53 protein and its phosphorylation at Ser15 through ERK and/or PIKK pathways. On the other hand, U0126 and PD98059 suppressed to some extent the cytotoxicity of acrylamide evaluated by trypan blue exclusion and lactate dehydrogenase (LDH) leakage, whereas neither LL-Z1640-2 nor wortmannin was effective in suppressing the toxicity. Thus, ERK pathway seems to play a role both in causing the phosphorylation of p53 at Ser15 and in the cytotoxicity of acrylamide in SH-SY5Y cells.
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PMID:Involvement of the extracellular signal-regulated protein kinase pathway in phosphorylation of p53 protein and exerting cytotoxicity in human neuroblastoma cells (SH-SY5Y) exposed to acrylamide. 1618 10

Low concentrations (nanomolar) of melatonin had been previously shown to inhibit cell proliferation in several cancer cell lines as well as in experimental animal models. Additionally, cell growth inhibition and differentiation of prostate cancer cell lines by high concentrations (micromolar to millimolar) of melatonin have been recently reported. In the present paper, we show the induction of apoptosis by high doses of melatonin in the human neuroblastoma cell line SK-N-MC. We found accumulation of cells in the G2/M cell cycle phase and induction of cellular death, measured as lactate dehydrogenase (LDH) released into the culture medium, under millimolar concentration of melatonin. Apoptosis was evaluated using 4,6-diamidino-2-phenylindole staining, DNA gel electrophoresis, electron microscopy, and annexin V binding. Apoptosis progressed through the classical pathway, which involves caspase-3 activation. Cell death was dose and time-dependent; the lowest effective concentration of melatonin was 100 microm. Treatment with 1 mm melatonin for 6 days induced cell death in 75% of the cells. This novel finding shows that a nontoxic natural indoleamine may be potential therapy for some types of human neuroblastomas.
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PMID:Melatonin induces apoptosis in human neuroblastoma cancer cells. 1687 18

It has been postulated that the pathogenesis of Parkinson's disease (PD) is associated with mitochondrial dysfunction. Rotenone, an inhibitor of mitochondrial complex I, provides models of PD both in vivo and in vitro. We investigated the neuroprotective effect of D-beta-hydroxybutyrate (bHB), a ketone body, against rotenone toxicity by using SH-SY5Y dopaminergic neuroblastoma cells. SH-SY5Y cells, differentiated by all-trans-retinoic acid, were exposed to rotenone at concentrations ranging from 0 to 1,000 nM. We evaluated cellular oxidation reduction by the alamarBlue assay, viability by lactate dehydrogenase (LDH) assay, and survival/death ratio by live/dead assays. Exposure to rotenone for 48 hr oxidized cells and decreased their viability and survival rate in a concentration-dependent manner. Pretreatment of cells with 8 mM bHB provided significant protection to SH-SY5Y cells. Whereas rotenone caused the loss of mitochondrial membrane potential, released cytochrome c into the cytosol, and reduced cytochrome c content in mitochondria, addition of bHB blocked this toxic effect. bHB also attenuated the rotenone-induced activation of caspase-9 and caspase-3. Administration of 0-10 mM 3-nitropropionic acid, a complex II inhibitor, also decreased the reducing power of SH-SY5Y cells measured by alamarBlue assay. Pretreatment with 8 mM bHB attenuated the decrease of alamarBlue fluorescence. These data demonstrated that bHB had a neuroprotective effect that supported the mitochondrial respiration system by reversing the inhibition of complex I or II. Ketone bodies, the alternative energy source in the mammalian brain, appear to have therapeutic potential in PD.
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PMID:D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease. 1691 40

Classical hallmarks of Alzheimer's disease (AD) are a synaptic loss, cholinergic neuron death, and abnormal protein deposition, particularly of toxic amyloid-beta peptide (Abeta) that is derived from amyloid-beta protein precursor (AbetaPP) by the action of beta- and gamma-secretases. The trigger(s) initiating the biochemical cascades that underpin these hallmarks have yet to be fully elucidated. The typical forebrain cholinergic cell demise associated with AD brain results in a loss of presynaptic cholinergic markers and acetylcholine (ACh). Neurine (vinyl-trimethyl-ammonium hydroxide) is a breakdown product of ACh, consequent to autolysis and is an organic poison found in cadavre brain. The time- and concentration-dependent actions of neurine were assessed in human neuroblastoma (NB, SK-N-SH) cells in culture by quantifying cell viability by lactate dehydrogenase (LDH) and MTS assay, and AbetaPP and Abeta levels by Western blot and ELISA. NB cells displayed evidence of toxicity to neurine at > or = 3 mg/ml, as demonstrated by elevated LDH levels in the culture media and a reduced cell viability shown by the MTS assay. Using subtoxic concentrations of neurine, elevations in AbetaPP and Abeta1-40 peptide levels were detected in conditioned media samples.
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PMID:Neurine, an acetylcholine autolysis product, elevates secreted amyloid-beta protein precursor and amyloid-beta peptide levels, and lowers neuronal cell viability in culture: a role in Alzheimer's disease? 1698 75

The cytotoxic effects of the herbicide alachlor were compared on rainbow trout gonadal RTG-2 and human neuroblastoma SH-SY5Y cell lines. The end points evaluated in both cells after 24, 48, and 72 h of exposure were total protein content (PC), lysosomal function, and mitochondrial's integrity by mitochondrial succinate dehydrogenase (SDH) activity. After 24 h, cytoplasmic membrane integrity by cytosolic lactate dehydrogenase (LDH) leakage and LDH intracellular activity were also studied. In addition, acetylcholinesterase activity (AChE) was quantified in SH-SY5Y cells. The possible biotransformation of alachlor by RTG-2 cells was investigated by analyzing the exposure culture medium by liquid chromatography-mass spectrometry. In RTG-2, EC50 values on PC, lysosomal function, and SDH activity after 24 h exposure ranged from 80 to 95 microM and decreased to approximately 40 microM for longer exposure time periods. SH-SY5Y cells were slightly more sensitive than RTG-2 cells, with EC50 values on PC and lysosomal function ranging from 87 to 75 microM at 24 h and decreasing to 47 microM and 34 microM at 72 h, respectively. AChE activity was increased, being the most sensitive marker for SH-SY5Y with an EC50 of 20 microM at 24 h. The metabolic enzyme SDH was stimulated in SH-SY5Y and reduced in RTG-2 cells. At the studied conditions, no metabolites of alachlor were detected in RTG-2 cultures. In conclusion, the proposed battery approach is an effective screening tool for the safety assessment of environmental contaminants as a complement to fish and animal toxicity procedures.
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PMID:Comparative cytotoxicity of alachlor on RTG-2 trout and SH-SY5Y human cells. 1699 29

Among the newly discovered amyloid properties, its cytotoxicity plays a key role. Lysozyme is a ubiquitous protein involved in systemic amyloidoses in vivo and forming amyloid under destabilising conditions in vitro. We characterized both oligomers and fibrils of hen lysozyme by atomic force microscopy and demonstrated their dose (5-50 microM) and time-dependent (6-48 h) effect on neuroblastoma SH-SY5Y cell viability. We revealed that fibrils induce a decrease of cell viability after 6 h due to membrane damage shown by inhibition of WST-1 reduction, early lactate dehydrogenase release, and propidium iodide intake; by contrast, oligomers activate caspases after 6 h but cause the cell viability to decline only after 48 h, as shown by fluorescent-labelled annexin V binding to externalized phosphatidylserine, propidium iodide DNA staining, lactate dehydrogenase release, and by typical apoptotic shrinking of cells. We conclude that oligomers induce apoptosis-like cell death, while the fibrils lead to necrosis-like death. As polymorphism is a common property of an amyloid, we demonstrated that it is not a single uniform species but rather a continuum of cross-beta-sheet-containing amyloids that are cytotoxic. An abundance of lysozyme highlights a universal feature of this phenomenon, indicating that amyloid toxicity should be assessed in all clinical applications involving proteinaceous materials.
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PMID:Lysozyme amyloid oligomers and fibrils induce cellular death via different apoptotic/necrotic pathways. 1713 16

The active form of 1,25-dihydroxyvitamin D(3) prevents neuronal damage in vitro and in vivo , however, it induces also hypercalcemia and hyperphosphatemia. Side-chain-modified analogues of 1,25-dihydroxyvitamin D(3), which show low calcemic activity, may be potentially useful in the treatment of some neurodegenerative diseases. Previously, we have found that PRI-2191 more potently than 1,25-dihydroxyvitamin D(3) protects human neuroblastoma (SH-SY5Y) cells against hydrogen-peroxide-induced toxicity. In the present study, we evaluated effects of two other 1,25-dihydroxyvitamin D(3) analogues - PRI-1890 and PRI-1901 on the neuronal degeneration in the same cell model. In line with the previous study, 24-h incubation with hydrogen peroxide (0.5 mM) was toxic to cells, as evidenced by an enhanced efflux of lactate dehydrogenase into the culture medium, and these effects were prevented by PRI-1890 and PRI-1901 at concentration of 5, 50 and 500 nM. Comparing the neuroprotective effects of secosteroids, we found that all three analogues were efficient at lower concentration than 1,25-dihydroxyvitamin D(3) and among them the PRI-2191 showed the most evident concentration-dependent effect. In the second part of this study, an involvement of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-K), kinases which play a crucial role in neurodegenerative processes, in neuroprotective action of 1,25 dihydroxyvitamin D(3) and its the most potent analogue PRI-2191 has been investigated. The inhibitor of c-Jun N-terminal kinase (JNK)-MAPK (SP600125, 1 microM), inhibitor of p38-MAPK (SB-203580, 1 and 10 microM) and inhibitor of extracellular signal-regulated kinase (ERK)-MAPK (PD-98059, 15 and 30 microM) attenuated the hydrogen peroxide-induced toxicity. Moreover, PD-98059 (30 microM) enhanced neuroprotective effects of 1,25 dihydroxyvitamin D(3) but not that of PRI-2191. In contrast, the inhibitor of PI3-K (wortmannin, 10, 100 nM) did not affect hydrogen peroxide-induced cell damage itself, however, it significantly antagonized the effect of PRI-2191. On the other hand, wortmannin did not affect the neuroprotective effects of 1,25 dihydroxyvitamin D(3) This suggests that the activation of PI3-K/Akt signaling pathway plays an important role in the mechanism of inhibitory action of PRI-2191 on hydrogen peroxide-evoked toxicity in SH-SY5Y cells. Furthermore, these data point to differential involvement of ERK-MAPK and PI3-K in neuroprotective effects of 1,25 dihydroxyvitamin D(3) and its low-calcemic analogue - PRI-2191.
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PMID:Involvement of PI3-K in neuroprotective effects of the 1,25-dihydroxyvitamin D3 analogue - PRI-2191. 1722 May 48

A proteomic approach was used to identify 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) protein targets in human neuroblastoma SH-SY5Y cells. By using biotinylated 15d-PGJ2, beta-actin was found as the major adducted protein; at least 12 proteins were also identified as minor biotin-positive spots, falling in different functional classes, including glycolytic enzymes (enolase and lactate dehydrogenase), redox enzymes (biliverdin reductase), and a eukaryotic regulatory protein (14-3-3gamma). 15d-PGJ2 induced marked morphological changes in the actin filament network and in particular promoted F-actin depolymerization as confirmed by Western blot analysis. By using a mass spectrometric approach, we found that 15d-PGJ2 reacts with isolated G-actin in a 1:1 stoichiometric ratio and selectively binds the Cys374 site through a Michael adduction mechanism. Computational studies showed that the covalent binding of 15d-PGJ2 induces a significant unfolding of actin structure and in particular that 15d-PGJ2 distorts the actin subdomains 2 and 4, which define the nucleotide binding sites impeding the nucleotide exchange. The functional effect of 15d-PGJ2 on G-actin was studied by polymerization measurement: in the presence of 15d-PGJ2, a lower amount of F-actin forms, as followed by the increase in pyrenyl-actin fluorescence intensity, as the major effect of increasing 15d-PGJ2 concentrations occurs on the maximum extent of actin polymerization, whereas it is negligible on the initial rate of reaction. In summary, the results here reported give an insight into the role of 15d-PGJ2 as a cytotoxic compound in neuronal cell dysfunction. Actin is the main protein cellular target of 15d-PGJ2, which specifically binds through a Michael adduction to Cys374, leading to a protein conformational change that can explain the disruption of the actin cytoskeleton, F-actin depolymerization, and impairment of G-actin polymerization.
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PMID:Identification of actin as a 15-deoxy-Delta12,14-prostaglandin J2 target in neuroblastoma cells: mass spectrometric, computational, and functional approaches to investigate the effect on cytoskeletal derangement. 1729 18

Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants. Because of their detection in human breast milk and structural similarity to polychlorinated biphenyls (PCBs), concern has been raised about their potential toxicity, particularly neurotoxic effects in newborns and children. The aim of the current study was to evaluate the cytotoxic and genotoxic effects of 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) in human neuroblastoma (SH-SY5Y) cells in vitro. SH-SY5Y cells were incubated with different concentrations of PBDE-47 (1, 2, 4, 8 microg/ml) for 24 h, and a set of bioassays were conducted to measure: cell viability, cell proliferation (nuclear division index, NDI), lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, cell apoptosis, and DNA breakage and cytogenetic damage. The data showed that PBDE-47 inhibited cell viability, increased LDH leakage, and induced cell apoptosis. All significant effects were observed at concentrations of 4 microg/ml and above (P<0.05). After 24 h exposure, a concentration-dependent increase in ROS formation was observed, and there were obviously increase in comparison to the control at concentrations as low as 2 microg/ml PBDE-47. Log-transformed Olive Tail Moment (OTM) were significantly increased compared with the control at various PBDE-47 concentrations (P<0.05), while a significant increase in the percentage of DNA in the tail was only observed at 8 microg/ml PBDE-47 (P<0.05). PBDE-47 caused a concentration-dependent decrease in NDI, and concentration-dependent increases in chromosome abnormalities as measured by total Micronuclei (MNi)/1000 binucleate cells (BNCs), micronucleated binucleate cells (MNBNCs)/1000 BNCs, and nucleoplasmic bridges (NPBs)/1000 BNCs. The results indicate that PBDE-47 is cytotoxic and genotoxic in SH-SY5Y cells in vitro.
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PMID:Effects of PBDE-47 on cytotoxicity and genotoxicity in human neuroblastoma cells in vitro. 1785 58

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