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)

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline), a metabolite of dopamine, may act as an endogenous neurotoxin and contribute to the etiology of Parkinson's disease (PD). The inverse relationship between smoking and PD prompted our previous investigation and the report of protective effects of nicotine against salsolinol-induced toxicity in cultured SH-SY5Y cells (Copeland et al., Neurotox. Res. 8:289, 2005). These cells, derived from human neuroblastoma cells, express dopaminergic activity and are used as a model of nigral dopaminergic cells, the major site of pathology in PD. The purpose of the current study was to investigate whether apoptotic or antiapoptotic mechanisms were responsible for the observed effects of salsolinol and nicotine, respectively. Moreover, it was of interest to determine whether the actions of nicotine are mediated through nicotinic receptors. SH-SY5Y cells were exposed to 0.4 or 0.7 mM salsolinol with and without pretreatment in combination of 0.1 mM nicotine and 0.1 mM mecamylamine and were exposed for 24 and 48 h. Various parameters including cell cycle perturbations (reflected in propidium iodide DNA staining); cell cycle regulator retinoblastoma protein (reflected in the Western blot), apoptosis (reflected in annexin V/propidium iodide staining followed by flow cytometry) were analyzed. Salsolinol caused an arrest of the cells in G1-phase of cell cycle and an increase in apoptotic indices, whereas pretreatment with nicotine attenuated or completely blocked the effects of salsolinol. Nicotine effects in turn, were totally blocked by mecamylamine (0.1 mM). The results suggest that apoptosis is a major mechanism for salsolinol-induced toxicity and that antiapoptotic effects of nicotine, mediated by nicotinic receptors, may play a primary role in its neuroprotective effects. Hence, nicotinic agonists in combination with other antiapoptotic agents may be of substantial benefit in at least a subpopulation of Parkinson patients.
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PMID:Antiapoptotic effects of nicotine in its protection against salsolinol-induced cytotoxicity. 1751

An isolate "CD lignan mixture" comprising lignans from stem wood of Cedrus deodara consisted of (-)-wikstromal (75 - 79%), (-)-matairesinol (9 - 13%) and benzylbutyrolactol (7 - 11%) and was studied for its in vitro cytotoxicity against human cancer cell lines. The in vivo anticancer activity of CD lignan mixture was studied using Ehrlich ascites carcinoma and colon carcinoma (CA-51) models in mice. Its effect was also studied on annexin V binding, intracellular caspases and DNA fragmentation to gain insight into the mode of action. In vitro cytotoxicity studies showed significant dose-dependent effects against several cancer cell lines from different tissues such as breast, cervix, neuroblastoma, colon, liver, and prostate at 10, 30 and 100 microg/mL. The IC (50) values varied from 16.4 ng/mL to 116.03 microg/mL depending on the cell line. Comparative data of IC (50) values of CD lignan mixture showed a synergistic effect in comparison to the individual molecules, i. e., (-)-matairesinol, (-)-wikstromol present in CD lignan mixture . CD lignan mixture had the most pronounced effect on CNS cell lines followed by colon. The tumor regression observed with Ehrlich ascites carcinoma and CA-51 was 53% and approximately 54%, respectively, when CD lignan mixture was given at 300 mg/kg, I. P. for nine days in the Ehrlich ascites carcinoma model and 400 mg/kg, I. P. for the same period in the CA-51 model. It was comparable with 5-fluorouracil at 22 mg/kg and 20 mg/kg, respectively. CD lignan mixture at 10, 30 and 100 microg/mL increased the percentage of annexin V positive HL-60 cells to 1.9 - 17.18% as compared to control (1.04%). In K562 cells CD lignan mixture at 10, 30 or 100 microg/mL and staurosporine (1 microM) showed 9.13%, 11.38%, 17.22% and 28.07% intracellular caspases activation, respectively. A distinct DNA laddering pattern was observed for treatment with the CD lignan mixture in HL-60, K562 (30 microg/mL and 100 microg/mL) and MOLT-4 cells (30 microg/mL) after 24 h incubation. DNA cell cycle analysis indicated that CD lignan mixture at 10, 30 and 100 microg/mL increased the content of hypodiploid (sub G(1) phase) cells when compared to control (2.55, 5.4 and 6.25% vs. 0.27%). The present study indicates that CD lignan mixture has cytotoxic potential against human cancer cell lines. It has the ability to induce tumor regression in vivo. It induces apoptosis as indicated by annexin V positive cells, induction of intracellular caspases, DNA fragmentation and DNA cell cycle analysis.
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PMID:Chemically standardized isolates from Cedrus deodara stem wood having anticancer activity. 1753 88

Dopamine (DA) is an oxidant that may contribute to the degeneration of dopaminergic neurons. The present study demonstrates that DA-induced cytotoxicity in human-derived neurotypic cells, SH-SY5Y, is prevented by resveratrol, one of the major antioxidative constituents found in the skin of grapes. SH-SY5Y cells, a neuroblastoma cell line, treated with DA at 300 and 500 microM for 24 h underwent apoptotic death as determined by characteristic morphological features, including nuclear condensation, and loss of mitochondrial membrane potential (MMP). Flow cytometric analysis using Annexin V showed that DA can induce significant and severe apoptosis. Exposure to resveratrol (5 microM) for 1 h prior to the DA treatment attenuated DA-induced cytotoxicity, and rescued the loss of MMP. To investigate the apoptotic signaling pathways relevant to the restoration of DA-induced apoptosis by resveratrol, we carried out quantitative analysis of Bcl-2, caspase-3, and cleaved poly ADP-ribose polymerase (PARP) by immunoblot analysis. Resveratrol pretreatment led to a decrease in cleavage of PARP, an increase in the Bcl-2 protein, and activation of caspase-3. These results suggest that DA may be a potential oxidant of neuronal cells at biologically relevant concentrations. Resveratrol may protect SH-SY5Y cells against this cytotoxicity, reducing intracellular oxidative stress through canonical signal pathways of apoptosis and may be of biological importance in the prevention of a dopaminergic neurodegenerative disorder such as Parkinson disease.
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PMID:Resveratrol protects SH-SY5Y neuroblastoma cells from apoptosis induced by dopamine. 1760 92

Curcumin has been shown to exhibit growth inhibitory effects and induce apoptosis in a broad range of tumors. Accordingly, we investigated the radiosensitizing effects of curcumin in human neuroblastoma cells. SK-N-MC cells exposed to either 2 Gy alone, or pretreated with curcumin (100 nM) or NFkappaB inhibitor peptide SN50 (50 nM) and exposed to 2 Gy were harvested after 48 h. Radioresistance was measured using clonogenic and MTT assay, NFkappaB DNA-binding activity using electrophoretic mobility shift assay, and apoptosis using Annexin V-FITC staining. Pathway (apoptosis) specific microarrays were used to measure gene expression and validated using QPCR. Radiation markedly enhanced the NFkappaB DNA-binding activity. Pre-treating the cells either with curcumin or SN50 significantly suppressed the radiation induced NFkappaB. Also, curcumin or SN50 pretreatment enhanced the radiation induced inhibition of cell survival. Microarray analysis revealed that curcumin enhanced the radiation induced activation of caspases, other pro-apoptotic and death effector molecules and, inhibit anti-apoptotic/survival molecules. In addition, curcumin markedly suppressed the radiation induced TNF super family genes. These results suggest that curcumin is a potent radiosensitizer and may act by overcoming the effects of radiation-induced NFkappaB mediated pro-survival gene expression in neuroblastoma.
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PMID:Curcumin inhibits NFkappaB mediated radioprotection and modulate apoptosis related genes in human neuroblastoma cells. 1830 9

Tight regulation of intracellular iron levels in response to mitochondrial dysfunction is an important mechanism that prevents oxidative stress, thereby limiting cellular damage. Here, we describe a cytoprotective response involving transcriptional activation of the ferritin H gene in response to the mitochondrial complex I inhibitor and neurotoxic compound rotenone. Rotenone exposure increased ferritin H mRNA and protein synthesis in NIH3T3 fibroblasts and SH-SY5Y neuroblastoma cells. Transient transfection of a ferritin H promoter-luciferase reporter into NIH3T3 cells showed that ferritin H was transcriptionally activated by rotenone through an antioxidant-responsive element (ARE). Chromatin immunoprecipitation assays showed that rotenone treatment enhanced binding of Nrf2 and JunD transcription factors to the ARE. In addition, rotenone induced production of reactive oxygen species (ROS), and pretreatment with N-acetylcysteine abrogated ferritin H mRNA induction by rotenone, suggesting that this response is oxidative stress-mediated. Furthermore, reduced ferritin H expression by siRNA sensitized cells to rotenone-induced apoptosis with increased ROS production and annexin V-positive cells. Taken together, these results suggest that ferritin H transcription is activated by rotenone via an oxidative stress-mediated pathway leading to ARE activation and may be critically important to protect cells from mitochondrial dysfunction and oxidative stress.
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PMID:Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress. 1832 46

Alzheimer's disease (AD) is a common neurodegenerative disorder, but the initiating molecular processes contributing to neuronal death are not well understood. AD is associated with elevated soluble and aggregated forms of amyloid beta (Abeta) and with oxidative stress. Furthermore, there is increasing evidence for a detrimental role of iron in the pathogenic process. In this context, iron chelation by compounds such as 3-hydroxypyridin-4-one, deferiprone (Ferriprox) may have potential neuroprotective effects. We have evaluated the possible neuroprotective actions of deferiprone against a range of AD-relevant insults including ferric iron, H(2)O(2) and Abeta in primary mouse cortical neurones. We have investigated the possible neuroprotective actions of deferiprone (1, 3, 10, 30 or 100 microM) in primary neuronal cultures following exposure to ferric iron [ferric nitrilotriacetate (FeNTA); 3 and 10 microM], H(2)O(2) (100 microM) or Abeta1-40 (3, 10 and 20 microM). Cultures were treated with deferiprone or vehicle either immediately or up to 6 h after the insult in a 24-well plate format. In order to elucidate a possible neuroprotective action of deferiprone against Parkinson's disease relevant insults another group of experiments were performed in the human neuroblastoma catecholaminergic SHSY-5Y cell line. SHSY-5Y cells were treated with MPP(+) iodide, the active metabolite of the dopaminergic neurotoxin MPTP and the neuroprotective actions of deferiprone evaluated. Cytotoxicity was assessed at 24 h by lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide turnover (FeNTA and hydrogen peroxide) and morphometric analysis of cell viability by Hoechst 33324/propidium iodide (FeNTA, Abeta and MPP(+)) or 6-carboxyfluorescein diacetate and annexin V-Cy3 (Abeta). The present study demonstrates that deferiprone protects against FeNTA, hydrogen peroxide, MPP(+) and Abeta1-40-induced neuronal cell death in vitro, which is consistent with previous in vitro and in vivo studies that have demonstrated similar protection with other iron chelators.
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PMID:Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y cells. 1833 85

We previously showed that neuregulin-1 (NRG-1) protected neurons from death in vivo following focal ischemia. The goal of this study was to develop an in vitro rat ischemia model to examine the cellular and molecular mechanisms involved in the neuroprotective effects of NRG-1 on ischemia-induced neuronal death. Rat B-35 neuroblastoma cells differentiated by serum withdrawal, developed enhanced neuronal characteristics including, neurite extension and upregulation of neuronal markers of differentiation. When B35 neurons were subjected to oxygen glucose deprivation (OGD)/reoxygenation or glutamate, widespread neuronal death was seen after both treatments. Treatment with NRG-1 immediately after OGD significantly increased neuronal survival. NRG-1 administration also resulted in a significant decrease in annexin V, an early marker of apoptosis. However, the neurotoxic actions of glutamate were unaffected by NRG-1. The neuroprotective effects of NRG-1 were prevented by an inhibitor of the phosphatidylinositol-3-kinase/Akt pathway. These results provide a new model to gain insight into the mechanisms employed by NRG-1 to protect neurons from ischemic brain injury.
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PMID:Neuroprotective effects of neuregulin-1 on B35 neuronal cells following ischemia. 1841 Sep 12

The aim of this study was to investigate whether radiofrequency (RF) fields characteristic of mobile phones at non-thermal levels can induce apoptosis in murine neuroblastoma (N2a) cells in both proliferating and differentiated states. Cells were exposed continuously for 24 h to one of the three 935-MHz RF signals: global system for mobile communication (GSM) basic, GSM talk and a continuous wave, unmodulated signal; all at a specific energy absorption rate of 2 W kg(-1). The measured increase in temperature of the cells due to the RF fields was around 0.06 degrees C. At a number of time points between 0 and 48 h post-exposure, the cells were assessed for apoptosis under a fluorescence microscope using three independent assays: Annexin V, caspase activation and in situ end-labelling. No statistically significant differences in apoptosis levels were observed between the exposed and sham-exposed cells using the three assays at any time point post-exposure. These data suggest that RF exposures, characteristic of GSM mobile phones, do not significantly affect the apoptosis levels in proliferating and differentiated murine neuroblastoma cell line N2a.
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PMID:Exposure to low level GSM 935 MHZ radiofrequency fields does not induce apoptosis in proliferating or differentiated murine neuroblastoma cells. 1855 May 13

This study is to explore the inhibitory effect of methyl jasmonate on cell proliferation and expression of XIAP and survivin of human neuroblastoma cell line BE(2)-C. After cultivation of 1 - 2 mmol x L(-1) jasmonates with BE (2) -C cells for 6 - 24 h, the growth inhibiting rates of BE (2) -C cells were studied by MTT colorimetry. Cell proliferation was detected by colony formation assay. Cell cycle phases were assayed by propidium iodide staining flow cytometery. Cell apoptosis was inspected by acridine orange-ethidium bromide fluorescent staining, Hoechst 33258 fluorescent staining, and Annexin V-FITC and propidium iodide staining flow cytometry. Expressions of cyclin D1, XIAP and survivin were determined by RT-PCR and real-time RT-PCR. Methyl jasmonate inhibited the growth of BE(2)-C cells in a dose- and time-dependent manner. After addition of 1, 1.5 and 2 mmol x L(-1) of methyl jasmonate for 24 h, the inhibiting rates of cell growth reached 20.6% - 85.5% (P < 0.01), and the IC50 was 1.35 mmol x L(-1). The cell cycles were arrested at S phase. A part of cells presented the characteristic morphological changes of apoptosis. The early apoptotic rates were 13.51%, 17.32%, 24.59% (P < 0.01) and the cell death rates were 29.36% , 54.73% , 75.52% (P < 0.01), respectively. The expression of XIAP and survivin mRNA were downregulated by 18.5% - 68.9% , 22.4% - 48.7% (P < 0.05), respectively, without change in that of cyclin D1. The results indicated that methyl jasmonate could significantly inhibit the growth of BE(2) -C cells through inducing cell cycle arrest and apoptosis, downregulating the expression of XIAP and survivin might be one of its molecular mechanisms of action.
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PMID:[Methyl jasmonate induces apoptosis of human neuroblastoma cell line BE(2) -C and its mechanism]. 1882 59

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


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