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)

Advanced glycation end product (AGE) accumulation in brain is believed to contribute to neuronal death in several neurodegenerative diseases. Neurons exposed to AGEs undergo oxidative stress, but the molecular mechanisms able to induce ROS generation and cell death are not yet clear. In this work, we exposed SH-SY5Y neuroblastoma cells to glycated albumin, as a model of AGE-modified protein, and we observed that cells differentiated by retinoic acid died after AGE exposure, through anion superoxide and peroxide generation, while undifferentiated cells resulted resistant. Retinoic acid induced marked increase in p47phox expression and in catalytic activity of PKC delta: the upregulation of a pathway involving NADPH oxidase and PKC delta is likely to be responsible for neuronal susceptibility to AGE. This hypothesis is confirmed by the fact that pre-treatments of differentiated cells with DPI, an inhibitor of NADPH oxidase, or with rottlerin, an inhibitor of PKC delta, were able to prevent AGE-induced neuronal death.
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PMID:PKC delta and NADPH oxidase in AGE-induced neuronal death. 1731 1

The amyloid beta-precursor protein (APP) and the Notch receptor are both type 1 integral transmembrane proteins, and both are cleaved by presenilin-dependent gamma-secretase activity. In this study, we have demonstrated that the Notch intracellular domain (Notch1-IC) suppresses APP-intracellular domain (AICD)-mediated ROS generation and cell death after being processed by gamma secretase. Notch1-IC physically interacts with AICD, Fe65, and Tip60, thereby disrupting the association of the AICD-Fe65-Tip60 trimeric transcription activator complex in AICD signaling. AICD-Fe65-Tip60 mediated reactive oxygen species generation was found to be suppressed by Notch1-IC. Furthermore, AICD-Fe65-Tip60 was shown to mediate cell death in human neuroblastoma cells, and the overexpression of Notch1-IC inhibited cell death induced by AICD-Fe65-Tip60. Collectively, our findings indicate that Notch1-IC plays the role of a negative regulator in AICD signaling via the disruption of the AICD-Fe65-Tip60 trimeric complex.
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PMID:Notch1 intracellular domain suppresses APP intracellular domain-Tip60-Fe65 complex mediated signaling through physical interaction. 1736 26

In recent years, a number of studies have implicated the potent antioxidant property of astaxanthin in various experimental systems; however, these studies employed only the all-trans isomer. On the other hand, it has been reported that all-trans natural astaxanthin is readily isomerized to cis-trans, especially 9-cis and 13-cis isomers, under certain conditions by chemical analysis; however, the biological activities of the cis isomers of astaxanthin are little known. In the present study, we investigated the antioxidant activity of 9-cis and 13-cis astaxanthin compared to the all-trans isomer in vitro. In a stable radical DPPH scavenging activity test and in rat microsome and rabbit erythrocyte ghost membrane lipid peroxidation systems induced by AAPH and t-BuOOH, respectively, the results apparently showed that cis-astaxanthin, especially 9-cis astaxanthin, exhibited a higher antioxidant effect than the all-trans isomer. In addition, during polyunsaturated fatty acid (PUFA) oxidation, both DHA and linoleic acid hydroperoxides formation were markedly inhibited by astaxanthin isomers addition in the order 9-cis >13-cis >all-trans. Furthermore, 9-cis also exhibited the most effective inhibition of the generation of ROS induced by 6-hydroxydopamine (6-OHDA) in human neuroblastoma SH-SY5Y cells among the astaxanthin isomers, as well as on the degradation of collagen type II induced by DHA and linoleic acid hydroperoxides. The above-mentioned results suggest, for the first time, that cis isomer astaxanthin, especially 9-cis astaxanthin, has a much higher antioxidant potency than that of the all-trans isomer.
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PMID:Cis astaxanthin and especially 9-cis astaxanthin exhibits a higher antioxidant activity in vitro compared to the all-trans isomer. 1741 51

Several studies support the hypothesis that neuroglobin and cytoglobin play a protective role against cell death when cellular oxygen supply is critical. Although the underlying molecular mechanisms are unknown, previous reports suggest that this protection can be realised by the fact that they act as ROS scavengers. In this study, expression of neuroglobin and cytoglobin was evaluated in a human neuroblastoma cell line (SH-SY5Y) under conditions of anoxia or oxygen and glucose deprivation (OGD). The cells could survive prolonged anoxia without significant loss of viability. They became anoxia sensitive when deprived of glucose. OGD induced significant cell death after 16 h resulting in 54% dead cells after 32 h. Necrosis was the main process involved in OGD-induced cell death. After reoxygenation, apoptotic neurons became more abundant. Real-time quantitative PCR and Western blotting revealed that neuroglobin and cytoglobin were upregulated, the former under OGD and the latter under anoxic conditions. Under OGD, cell survival was significantly reduced after inhibiting cytoglobin expression by transfection with antisense ODN. Moreover, cell survival was significantly enhanced by neuroglobin or cytoglobin overexpression. When neuroglobin or cytoglobin protein expression increased or decreased, the H(2)O(2) level was found to be lower or higher, respectively. We conclude that neuroglobin or cytoglobin act as ROS scavengers under ischemic conditions.
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PMID:Anoxia or oxygen and glucose deprivation in SH-SY5Y cells: a step closer to the unraveling of neuroglobin and cytoglobin functions. 1753 79

Morphine is recommended as a first-line opioid analgesic in the pain management of cancer patients. Accumulating evidence shows that morphine has anti-apoptotic activity, but its impact on the therapeutic applications of antineoplastic drugs is not well known. The present study was undertaken to test the hypothesis that morphine might antagonize the pro-apoptotic activity of DOX (doxorubicin), a commonly used antitumour drug for the treatment of neuroblastoma, in cultured SH-SY5Y cells. In the present study we demonstrated that morphine suppressed DOX-induced inhibition of cell proliferation and programmed cell death in a concentration-dependent, and naloxone as well as pertussis toxin-irreversible, manner. Further studies showed that morphine inhibited ROS (reactive oxygen species) generation, and prevented DOX-mediated caspase-3 activation, cytochrome c release and changes of Bax and Bcl-2 protein expression. The antioxidant NAC (N-acetylcysteine) also showed the same effects as morphine on DOX-induced ROS generation, caspase-3 activation and cytochrome c release and changes in Bax (Bcl-2-associated X protein) and Bcl-2 protein expression. Additionally, morphine was found to suppress DOX-induced NF-kappaB (nuclear factor kappaB) transcriptional activation via a reduction of IkappaBalpha (inhibitor of nuclear factor kappaB) degradation. These present findings support the hypothesis that morphine can inhibit DOX-induced neuroblastoma cell apoptosis by the inhibition of ROS generation and mitochondrial cytochrome c release, as well as by blockade of NF-kappaB transcriptional activation, and suggests that morphine might have an impact on the antitumour efficiency of DOX.
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PMID:Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappaB transcriptional activation in neuroblastoma SH-SY5Y cells. 1754 80

(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

Hypoxia is a prominent feature of solid tumor development and is known to stimulate mitochondrial ROS (mROS), which, in turn, can activate hypoxia-inducible transcription factor-1alpha and nuclear factor-kappaB (NF-kappaB). Because NF-kappaB plays a central role in carcinogenesis, we examined the mechanism of mROS-mediated NF-kappaB activation and the fate of cancer cells during hypoxia after mitochondrial reduced glutathione (mGSH) depletion. Hypoxia generated mROS in hepatoma (HepG2, H35), neuroblastoma (SH-SY5Y), and colon carcinoma (DLD-1) cells, leading to hypoxia-inducible transcription factor-1alpha-dependent gene expression and c-Src activation that was prevented in cells expressing a redox-insensitive c-Src mutant (C487A). c-Src stimulation activated NF-kappaB without IkappaB-alpha degradation due to IkappaB-alpha tyrosine phosphorylation that was inhibited by rotenone/TTFA or c-Src antagonism. The c-Src-NF-kappaB signaling contributed to the survival of cells during hypoxia as c-Src inhibition or p65 down-regulation by small interfering RNA-sensitized HepG2 cells to hypoxia-induced cell death. Moreover, selective mGSH depletion resulted in an accelerated and enhanced mROS generation by hypoxia that killed SH-SY5Y and DLD-1 cells without disabling the c-Src-NF-kappaB pathway. Thus, although mROS promote cell survival by NF-kappaB activation via c-Src, mROS overgeneration may be exploited to sensitize cancer cells to hypoxia.
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PMID:Dual role of mitochondrial reactive oxygen species in hypoxia signaling: activation of nuclear factor-{kappa}B via c-SRC and oxidant-dependent cell death. 1767 Dec 7

Exposure to rotenone, a widely used pesticide, has been suggested to increase the risk of developing Parkinson's disease. Studies indicate that the neurotoxicity of rotenone may be related to its ability to generate reactive oxygen species. The present work was conducted to determine to what extent (-)-epigallocatechin-3-gallate (EGCG), a widely used dietary supplement, modulates the cytotoxicity of rotenone in human neuroblastoma SH-SY5Y cells. Our results indicate that EGCG shows concentration-dependent effects on ROS production and cytotoxicity in SH-SY5Y cells. Treatment of these dopaminergic cells with rotenone (1-50 microM) alone or EGCG (25 or 50 microM) alone caused a significant decrease in cell viability. Pretreatment of SH-SY5Y cells with 25 or 50 microM EGCG potentiated the cytotoxicity of rotenone. The exacerbating effect of EGCG on rotenone toxicity may involve an apoptotic mechanism as shown by the enhancement of caspase-3 activity and activation of other caspases in rotenone-treated SH-SY5Y cells. The potentiating effect of EGCG on rotenone toxicity may be attributed to the enhanced production of intracellular superoxide in SH-SY5Y cells. The enhanced intracellular production of ROS by rotenone-EGCG combination may also account for the increased formation of protein carbonyls in 10,000xg fraction of SH-SY5Y cells detected by anti-HNE antibody. For instance, core histones and nuclear ribonuclear proteins were identified as major putative in vivo targets of HNE. Our present findings indicate that more detailed mechanistic studies are necessary to fully understand the chemistry of EGCG and to justify its use as potentially health-promoting dietary supplement, e.g. in the prevention of neurodegenerative diseases associated with oxidative stress.
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PMID:Epigallocatechin gallate (EGCG) potentiates the cytotoxicity of rotenone in neuroblastoma SH-SY5Y cells. 1790 May 45

Many herbal medicines and dietary supplements sold as aids to improve memory or treat neurodegenerative diseases or have other favorable effects on the CNS contain a catechol or similar 1,2-dihydroxy aromatic moiety in their structure. As an approach to isolate and examine the neuroprotective properties of catechols, a simple catechol 4-t-Butylcatechol (TBC) has been used as a model. In this study, we investigated the effects of TBC on lipopolysaccharide (LPS)-activated microglial-induced neurotoxicity by using the in vitro model of coculture murine microglial-like cell line HAPI with the neuronal-like human neuroblastoma cell line SH-SY5Y. We also examined the effects of TBC on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. TBC at concentrations from 0.1-10 microM had no toxic effect on HAPI cells and SH-SY5Y cells, and it inhibited LPS (100 ng/ml)-induced increases of superoxide, intracellular ROS, gp91(Phox), iNOS and a decrease of HO-1 in HAPI cells. Under coculture condition, TBC significantly reduced LPS-activated microglia-induced dopaminergic SH-SY5Y cells death. Moreover, TBC (0.1-10 microM) inhibited 6-OHDA-induced increases of intracellular ROS, iNOS, nNOS, and a decrease of mitochondria membrane potential, and cell death in SH-SY5Y cells. However, the neurotoxic effects of TBC (100 microM) on SH-SY5Y cells were also observed including the decrease in mitochondria membrane potential and the increase in COX-2 expression and cell death. TBC-induced SH-SY5Y cell death was attenuated by pretreatment with NS-398, a selective COX-2 inhibitor. In conclusion, this study suggests that TBC might possess protective effects on inflammation- and oxidative stress-related neurodegenerative disorders. However, the high concentration of TBC might be toxic, at least in part, for increasing COX-2 expression.
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PMID:Neuronal effects of 4-t-Butylcatechol: a model for catechol-containing antioxidants. 1819 Sep 40

Although Naja naja atra cardiotoxin 3 (CTX3) and cardiotoxin 4 (CTX4) showed different cytotoxicity toward human neuroblastoma SK-N-SH cells, the two toxins induced apoptotic death on SK-N-SH cells. The apoptosis signals of CTX3 and CTX3 included ROS generation, increase in mitochondrial permeability transition, cytochrome c release to the cytosol and activation of caspase-9 and -3. However, CTX3 quickly induced the effects with higher magnitude compared with CTX4. ROS production and subsequent apoptotic cell death in CTX-treated cells were partly blocked by the antioxidant 2,3-dihydroxybenzoic acid. Nevertheless, mitochondria alteration and cytosolic cytochrome c release were not significantly attenuated by the antioxidant. Cell death was not completely inhibited by caspase-3 inhibitor. Moreover, cyclosporine A, an inhibitor of mitochondrial permeability transition, slightly decreased CTX-induced ROS generation by approximately 15%. Taken together, our data indicate that N. naja atra CTXs induce ROS generation that is not wholly dependent on mitochondrial dysfunction, and that the cytotoxic potency of CTX3 and CTX4 on SK-N-SH cells is, at least in part, correlated with their capability in inducing ROS generation and mitochondrial alterations.
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PMID:Taiwan cobra cardiotoxins induce apoptotic death of human neuroblastoma SK-N-SH cells mediated by reactive oxygen species generation and mitochondrial depolarization. 1822 63


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