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)

(1) Morroniside belongs to an extensive group of natural iridorid glycosides. In the present study, using human neuroblastoma SH-SY5Y cells, we have investigated the protective effects of this compound on modifications in endogenous reduced glutathione (GSH), intracellular oxygen species (ROS) and apoptotic death on H(2)O(2)-mediated cytoxicity. (2) Incubation of cells with morroniside led to a significant dose-dependent elevation of cellular GSH accompanied by a marked protection against H(2)O(2)-mediated toxicity. Morroniside at 1-100 microM inhibited the formation of ROS and the activation of caspase-3 and 9, and the upregulation of Bcl-2, whereas no significant change occurred in Bax levels. (3) The results indicated that the anti-oxidative and anti-apoptotic properties render this natural compound potentially protective against H(2)O(2)-induced cytotoxicity. (4) This study suggested that intracellular GSH appeared to be an important factor in morroniside-mediated cytoprotection against H(2)O(2)-toxicity in SH-SY5Y cells.
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PMID:Morroniside prevents peroxide-induced apoptosis by induction of endogenous glutathione in human neuroblastoma cells. 1764 2

Dopamine (DA), as a neurotoxin, can elicit severe Parkinson's disease-like syndrome by elevating intracellular reactive oxygen species (ROS) levels and apoptotic activity. In this study, we examined the effect of esculin, which was extracted from Fraxinus sielboldiana blume, on DA-induced cytotoxicity and the underlying mechanism in human neuroblastoma SH-SY5Y cells. Our results suggest that the protective effects of esculin (10(-7), 10(-6) and 10(-5) M) on DA-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing ROS level, and its anti-apoptotic effect via protecting mitochondrion membrane potential (DeltaPsim), enhancing superoxide dismutaese (SOD) activity and reduced glutathione (GSH) levels, and regulating P53, Bax and Bcl-2 expression. In addition, esculin inhibited the release of cytochrome c and apoptosis-inducing factor (AIF), and the protein expression of activated caspase 3. These data indicate that esculin may provide a useful therapeutic strategy for the treatment of progressive neurodegenerative diseases such as Parkinson's disease (PD).
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PMID:Anti-apoptotic effect of esculin on dopamine-induced cytotoxicity in the human neuroblastoma SH-SY5Y cell line. 1790 93

Alpha-lipoic acid (LA) has recently been reported to afford protective effects in neurodegenerative disorders. However, the mechanisms underlying LA-mediated neuroprotection remain to be investigated. This study was undertaken to determine whether LA treatment could increase endogenous antioxidants and phase 2 enzymes in cultured human neuroblastoma SH-SY5Y cells, and whether such increased cellular defenses could afford protection against cytotoxicity induced by neurotoxicants. Incubation of SH-SY5Y cells with micromolar concentrations of LA for 24 h resulted in a significant increase in the levels of reduced glutathione (GSH) and NAD(P)H:quinone oxidoreductase 1 (NQQ1) in a concentration-dependent fashion. Treatment of the cells with LA also led to an increased mRNA expression of gamma-glutamylcysteine ligase catalytic subunit (GCLC) and NQO1. To determine the protective effects of the LA-induced cellular defenses on neurotoxicant-elicitedl cell injury, SH-SY5Y cells were pretreated with LA for 24 h and then exposed to acrolein, 4-hydroxy-2-nonenal (HNE), H(2)O(2) and the peroxynitrite generator, 3-morpholinosydnonimine (SIN-1). We observed that LA pretreatment of SH-SY5Y cells led to a marked protection against acrolein, HNE, H(2)O(2 )and SIN-1-mediated cytotoxicity, as detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium reduction assay. Taken together, this study demonstrates for the first time that LA can induce GSH and NQO1 in cultured human neuroblastoma cells and LA-upregulated cellular defenses are accompanied by a markedly increased resistance to cytotoxicity induced by various neurotoxicants. The results of this study may have important implications for the neuroprotective effects of LA.
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PMID:Potent upregulation of glutathione and NAD(P)H:quinone oxidoreductase 1 by alpha-lipoic acid in human neuroblastoma SH-SY5Y cells: protection against neurotoxicant-elicited cytotoxicity. 1794 Aug 86

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

Environmental substances or metabolites induce neuronal damage through oxidative stress. Environmental organic solvent metabolite, 1,2-diacetylbenzene (1,2-DAB), treated rats develop limb weakness with neuropathological damage in both the central and peripheral nervous systems. In this experiment, we examined the relevance of 1,2-DAB-induced toxicity to increased oxidative stress using human dopaminergic neuroblastoma SHSY5Y cells. 1,2-DAB (4, 16, and 32 microM) disrupted cytoskeletal integrity and caused morphological changes. 1,2-DAB significantly decreased cell viability and induced cell cycle arrest in the G(1) phase in a concentration-dependent manner. At higher concentration, it produced apoptosis. Pre-treatment of cells with the antioxidants, GSH or N-acetylcysteine (NAC), effectively blocked 1,2-DAB-mediated cytotoxicity including cell viability, and morphological changes. These results therefore suggest that oxidative stress is involved in environmental metabolite 1,2-DAB-mediated neurotoxicity and that antioxidant treatment can effectively protect the nervous system from environmental hazards.
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PMID:Cytotoxicity of 1,2-diacetylbenzene in human neuroblastoma SHSY5Y cells is mediated by oxidative stress. 1806 64

Depletion of glutathione (GSH) by buthionine sulfoximine (BSO) has been reported to be toxic against some cancer cells and to sensitize many tumours including neuroblastoma (NB) to anticancer drugs. The balance between the production rate of reactive oxygen species (ROS) and the function of GSH affects the intracellular reduction-oxidation status, which is crucial for the regulation of several cellular physiological functions. To assess the role of glutathione in neuroblastoma therapy, the effect of sublethal concentrations of BSO was studied in a panel of neuroblastoma cell lines characterized by different MYCN status. We found that GSH depletion per se not accompanied by ROS overproduction, does not affect cell survival, and is not genotoxic but induces HO-1 expression in GI-ME-N cell line, a representative example of MYCN non-amplified NB cells, having the highest basal levels of GSH among the tested NB lines. These observations might open a novel therapeutic window based on the possibility of modulating the cellular 'activity' of GSH.
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PMID:GSH loss per se does not affect neuroblastoma survival and is not genotoxic. 1809 50

Dopamine, as a neurotoxin, can elicit severe Parkinson's disease-like syndrome by elevating intracellular reactive oxygen species levels and apoptotic activity. In this study, we examined the effect of 6,7-di-O-glucopyranosyl-esculetin, which was extracted from Fraxinus sieboldiana bloom, on dopamine-induced cytotoxicity and the underlying mechanism in human neuroblastoma SH-SY5Y cells. Our results suggest that the protective effects of 6,7-di-O-glucopyranosyl-esculetin (0.1, 1 and 10 microM) on dopamine-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing reactive oxygen species levels, and its anti-apoptotic effect via protecting mitochondrion membrane potential (Delta Psi m), enhancing superoxide dismutaese (SOD) activity and reduced glutathione (GSH) levels, and regulating p53, Bax and Bcl-2 expression. In addition, 6,7-di-O-glucopyranosyl-esculetin inhibited the release of cytochrome c and apoptosis-inducing factor (AIF), and the protein expression of activated caspase 3. These data indicate that 6,7-di-O-glucopyranosyl-esculetin may provide a useful therapeutic strategy for the treatment of progressive neurodegenerative diseases such as Parkinson's disease.
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PMID:6,7-di-O-glucopyranosyl-esculetin protects SH-SY5Y cells from dopamine-induced cytotoxicity. 1817 36

Evidence suggests oxidative and electrophilic stress as a major factor contributing to the neuronal cell death in neurodegenerative disorders, especially Parkinson's disease. Consistent with this concept, administration of exogenous antioxidants has been shown to be protective against oxidative/electrophilic neurodegeneration. However, whether induction of endogenous antioxidants and phase 2 enzymes by the unique chemoprotectant, 3H-1,2-dithiole-3-thione (D3T) in neuronal cells also affords protection against oxidative and electrophilic neurocytotoxicity has not been carefully investigated. In this study, we showed that incubation of SH-SY5Y neuroblastoma cells or primary human neurons with micromolar concentrations (10-100 microM) of D3T for 24 h resulted in significant increases in the levels of reduced glutathione (GSH) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two crucial cellular defenses against oxidative and electrophilic stress. D3T treatment also caused increases in mRNA expression of gamma-glutamylcysteine ligase catalytic subunit and NQO1 in SH-SY5Y cells. In addition, D3T treatment of the neuronal cells also resulted in a marked elevation of GSH content in the mitochondrial compartment. To determine the protective effects of the D3T-induced cellular defenses on neurotoxicant-elicited cell injury, SH-SY5Y cells were pretreated with D3T for 24 h and then exposed to dopamine, 6-hydroxydopamine (6-OHDA), 4-hydroxy-2-nonenal (HNE), or H2O2, agents that are known to be involved in neuron degeneration. We observed that D3T-pretreatment of SH-SY5Y cells led to significant protection against the cytotoxicity elicited by the above neurotoxicants. Similar neurocytoprotective effects of D3T-pretreatment were also observed in primary human neurons exposed to 6-OHDA or HNE. Taken together, this study demonstrates that D3T potently induces neuronal cellular GSH and NQO1 as well as mitochondrial GSH, and that such upregulated endogenous defenses are accompanied by increased resistance to oxidative and electrophilic neurocytotoxicity.
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PMID:Potent induction of total cellular GSH and NQO1 as well as mitochondrial GSH by 3H-1,2-dithiole-3-thione in SH-SY5Y neuroblastoma cells and primary human neurons: protection against neurocytotoxicity elicited by dopamine, 6-hydroxydopamine, 4-hydroxy-2-nonenal, or hydrogen peroxide. 1823 65

Selenium (Se) is an essential micronutrient as well as a toxic trace element in animal and human nutrition. The effects of Se in the immune system and some diseases are well documented. The objective of the present study was to examine the role of Se in reducing the hypoxia induced apoptosis in neuroblastoma cell line. Hypoxia showed an enhanced cytotoxicity, increased free radical production and apoptosis (p<0.001) which was measured in terms of DNA break down by comet assay. Hypoxia has decreased reduced Glutathione (GSH) content, Glutathione Reductase (GR), Glutathione peroxidase (GPx) and Superoxide Dismutase (SOD) activities as compared to control cells. During hypoxic condition the expression of cytochrome C, pro and active caspase-3 levels were enhanced significantly followed by nonsignificant upregulation of Bcl-2. But, the Se supplementation inhibited the cytotoxicity, free radical generation and stabilized the HIF-1alpha accumulation in cells under hypoxia. The GSH content, GR, GPx and SOD activities increased significantly in Se-treated hypoxic cells, as compared to control. Further there was an appreciable inhibition of apoptosis by upregulation of Bcl-2 proteins, in the presence of Se under hypoxia. Selenium supplementation to cells significantly inhibited the hypoxia induced DNA fragmentation and restored the antioxidant status back to control levels. This study suggests that Se supplementation prevented the cells from hypoxia induced apoptosis by triggering upregulation of Bcl-2 protein and reducing the oxidative stress.
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PMID:Selenium protects the hypoxia induced apoptosis in neuroblastoma cells through upregulation of Bcl-2. 1840 86

Poly(ADP-ribose) polymerase (PARP) activation plays a role in repairing injured DNA, while its overactivation is involved in various diseases, including neuronal degradation. In the present study, we investigated the use of a PARP inhibitor, 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), whether methylmercury-induced cell death in the primary culture of cerebellar granule cells involved PARP activation. DPQ decreased the methylmercury-induced cell death in a dose-dependent manner. Unexpectedly, this protective effect was DPQ specific; none of the other PARP inhibitors--1,5-dihydroxyisoquinoline, 3-aminobenzamide, or PJ34--affected neuronal cell death. Methylmercury-induced cell death involves the decrease of glutathione (GSH) and production of reactive oxygen species. Therefore, to understand the mechanism by which DPQ inhibits cytotoxicity, we first studied the effect of DPQ on buthionine sulfoximine- or diethyl maleate-induced death of primary cultured cells and human neuroblastoma IMR-32 cells, both of which are mediated by GSH depletion. DPQ inhibited the cell death of both cultured cells, but it did not restore the decrease of cellular GSH by buthionine sulfoximine to the control level. Second, we evaluated the antioxidant activity of PARP inhibitors by methods with ABTS (2-2'-azinobis(3-ethylbenzothiazoline 6-sulfonate) or DPPH (1,1-diphenyl-2-picrylhydrazyl) used as a radical because antioxidants also efficiently suppress methylmercury-induced cell death. The antioxidant activity of DPQ was the lowest among the tested PARP inhibitors. Taken together, our results indicate that DPQ effectively protects cells against methylmercury- and GSH depletion-induced death. Furthermore, they suggest that DPQ exerts its protective effect through a mechanism other than PARP inhibition and direct antioxidation, and that PARP activation is not involved in methylmercury-induced neuronal cell death.
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PMID:Involvement of independent mechanism upon poly(ADP-ribose) polymerase (PARP) activation in methylmercury cytotoxicity in rat cerebellar granule cell culture. 1862 28


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