prostaglandin-a1 and Neuroblastoma
prostaglandin-a1 has been researched along with Neuroblastoma* in 6 studies
Other Studies
6 other study(ies) available for prostaglandin-a1 and Neuroblastoma
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Overexpression of amyloid precursor protein is associated with degeneration, decreased viability, and increased damage caused by neurotoxins (prostaglandins A1 and E2, hydrogen peroxide, and nitric oxide) in differentiated neuroblastoma cells.
Inflammatory reactions are considered one of the important etiologic factors in the pathogenesis of Alzheimer's disease (AD). Prostaglandins such as PGE2 and PGA1 and free radicals are some of the agents released during inflammatory reactions, and they are neurotoxic. The mechanisms of their action are not well understood. Increased levels of beta-amyloid fragments (Abeta40 and Abeta42), generated through cleavage of amyloid precursor protein (APP), oxidative stress, and proteasome inhibition, are also associated with neurodegeneration in AD brains. Therefore, we investigated the effect of PGs and oxidative stress on the degeneration and viability of cyclic AMP-induced differentiated NB cells overexpressing wild-type APP (NBP2-PN46) under the control of the CMV promotor in comparison with differentiated vector (NBP2-PN1) or parent (NBP2) control cells. Results showed that differentiated NBP2-PN46 cells exhibited enhanced spontaneous degeneration and decreased viability in comparison with differentiated control cells, without changing the level of Abeta40 and Abeta42. PGA1 or PGE2 treatment of differentiated cells caused increased degeneration and reduced viability in all three cell lines. These effects of PGs are not due to alterations in the levels of vector-derived APP mRNA or human APP holoprotein, secreted levels of Abeta40 and Abeta42, or proteasome activity. H2O2 or SIN-1 (an NO donor) treatment did not change vector-derived APP mRNA levels, but H2O2 reduced the level of human APP protein more than SIN-1. Furthermore, SIN-1 increased the secreted level of Abeta40, but not of Abeta42, whereas H2O2 had no effect on the level of secreted Abeta fragments. Both H2O2 and SIN-1 inhibited proteasome activity in the intact cells. The failure of neurotoxins to alter APP mRNA levels could be due to the fact that they do not affect CMV promoter activity. These results suggest that the mechanisms of action of PGs on neurodegeneration are different from those of H2O2 and SIN-1 and that the mechanisms of neurotoxicity of H2O2 and SIN-1 are, at least in part, different from each other. Topics: Amyloid beta-Protein Precursor; Animals; Cell Differentiation; Cell Line; Cell Survival; Dinoprostone; Dose-Response Relationship, Drug; Down-Regulation; Gene Expression Regulation; Humans; Hydrogen Peroxide; Mice; Nerve Degeneration; Neuroblastoma; Neurotoxins; Nitric Oxide; Prostaglandins A; Tumor Cells, Cultured | 2003 |
Prostaglandin A1 inhibits rotenone-induced apoptosis in SH-SY5Y cells.
The degeneration of nigral dopamine neurons in Parkinson's disease (PD) reportedly involves a defect in brain mitochondrial complex I in association with the activation of nuclear factor-kappaB (NF-kappaB) and caspase-3. To elucidate molecular mechanisms possibly linking these events, as well as to evaluate the neuroprotective potential of the cyclopentenone prostaglandin A1 (PGA1), an inducer of heat shock proteins (HSPs), we exposed human dopaminergic SH-SY5Y cells to the complex I inhibitor rotenone. Dose-dependent apoptosis was preceded by the nuclear translocation of NF-kappaB and then the activation of caspase-3 over the ensuing 24 h. PGA1 increased the expression of HSP70 and HSP27 and protected against rotenone-induced apoptosis, without increasing necrotic death. PGA1 blocked the rotenone-induced nuclear translocation of NF-kappaB and attenuated, but did not abolish, the caspase-3 elevation. Unexpectedly, the caspase-3 inhibitor, Ac-DEVD.CHO (DEVD), at a concentration that completely prevented the caspase-3 elevation produced by rotenone, failed to protect against apoptosis. These results suggest that complex I deficiency in dopamine cells can induce apoptosis by a process involving early NF-kappaB nuclear translocation and caspase-3 activation. PGA1 appears to protect against rotenone-induced cell death by inducing HSPs and blocking nuclear translocation of NF-kappaB in a process that attenuates caspase-3 activation, but is not mediated by its inhibition. Topics: Active Transport, Cell Nucleus; Apoptosis; Caspase 3; Caspase Inhibitors; Caspases; Cell Line; Dose-Response Relationship, Drug; Enzyme Inhibitors; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; Molecular Chaperones; Neoplasm Proteins; Neuroblastoma; Neurons; Neuroprotective Agents; NF-kappa B; Prostaglandins A; Rotenone; Uncoupling Agents | 2002 |
Activation of I kappa b kinase by herpes simplex virus type 1. A novel target for anti-herpetic therapy.
Herpes simplex viruses (HSV) are ubiquitous pathogens causing a variety of diseases ranging from mild illness to severe life-threatening infections. HSV utilize cellular signaling pathways and transcription factors to promote their replication. Here we report that HSV type 1 (HSV-1) induces persistent activation of transcription factor NF-kappa B, a critical regulator of genes involved in inflammation, by activating the I kappa B kinase (IKK) in the early phase of infection. Activated NF-kappa B enhances HSV-1 gene expression. HSV-1-induced NF-kappa B activation is dependent on viral early protein synthesis and is not blocked by the anti-herpetic drug acyclovir. IKK inhibition by the anti-inflammatory cyclopentenone prostaglandin A(1) blocks HSV-1 gene expression and reduces virus yield by more than 3000-fold. The results identify IKK as a potential target for anti-herpetic drugs and suggest that cyclopentenone prostaglandins or their derivatives could be used in the treatment of HSV infection. Topics: Acyclovir; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Chlorocebus aethiops; Cycloheximide; Dactinomycin; Drug Design; Enzyme Activation; Enzyme Inhibitors; Gene Expression Regulation, Fungal; Herpesvirus 1, Human; Humans; I-kappa B Kinase; Kinetics; Laryngeal Neoplasms; Methionine; Neuroblastoma; NF-kappa B; Prostaglandins A; Protein Serine-Threonine Kinases; Recombinant Proteins; Transfection; Tumor Cells, Cultured; Vero Cells; Virus Replication | 2001 |
Prostaglandins act as neurotoxin for differentiated neuroblastoma cells in culture and increase levels of ubiquitin and beta-amyloid.
Although chronic inflammatory reactions have been proposed to cause neuronal degeneration associated with Alzheimer's disease (AD), the role of prostaglandins (PGs), one of the secretory products of inflammatory reactions, in degeneration of nerve cells has not been studied. Our initial observation that PGE1-induced differentiated neuroblastoma (NB) cells degenerate in vitro more rapidly than those induced by RO20-1724, an inhibitor of cyclic nucleotide phosphodiesterase, has led us to postulate that PGs act as a neurotoxin. This study has further investigated the effects of PGs on differentiated NB cells in culture. Results showed that PGA1 was more effective than PGE1 in causing degeneration of differentiated NB cells as shown by the cytoplasmic vacuolation and fragmentation of soma, nuclei, and neurites. Because increased levels of ubiquitin and beta-amyloid have been implicated in causing neuronal degeneration, we studied the effects of PGs on the levels of these proteins during degeneration of NB cells in vitro by an immunostaining technique, using primary antibodies to ubiquitin and beta-amyloid. Results showed that PGs increased the intracellular levels of ubiquitin and beta-amyloid prior to degeneration, whereas the degenerated NB cells had negligible levels of these proteins. These data suggest that PGs act as external neurotoxic signals which increase levels of ubiquitin and beta-amyloid that represent one of the intracellular signals for initiating degeneration of nerve cells. Topics: 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; Alprostadil; Amyloid beta-Peptides; Animals; Bucladesine; Cell Differentiation; Culture Media, Serum-Free; Mice; Neuroblastoma; Neurotoxins; Prostaglandins A; Staining and Labeling; Tumor Cells, Cultured; Ubiquitins | 1998 |
Role of adenosine 3'5'-cyclic monophosphate in antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1) on human neuroblastoma cells.
To determine the role of adenosine 3'5'-cyclic monophosphate (cAMP) in the antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1), we studied 2 cell lines of human neuroblastoma; i.e. GOTO and SK-N-DZ. PGE1 or E2 at 30 micrograms/ml and PGD2 or PGA1 at 5 micrograms/ml were cytotoxic to these neuroblastoma cells. In both cell lines, increase of intracellular cAMP was closely associated with E-type PGs cytotoxicity, however, in PGD2, or PGA1 cytotoxicity, cAMP increase was observed only in GOTO cells. Pretreatment of GOTO cells with 5 micrograms/ml PGE2 for 24 hr caused a desensitization of cAMP responses to PGE1, PGD2 or PGA1 only in association with a reduced cytotoxicity of PGE1. On the other hand, PGE2-pretreated SK-N-DZ cells resulted in a desensitization in response to PGE1, but not to other PGs, without affecting the cytotoxicity of these PGs. A decreased [3H]PGE1 binding similarly occurred in either the PGE2-pretreated GOTO or SK-N-DZ cells. However, cholera toxin- or forskolin-induced cAMP production was suppressed only in the pretreated GOTO cells. cAMP response by forskolin rather increased in the pretreated SK-N-DZ cells. These results indicate that antineoplastic effect of E type PGs mediates through cAMP, but not that of PGD2 and PGA1 and that PGE2 pretreatment may cause a down regulation of PGE1 receptor site in both cell lines. It is also suggested that PGE2 pretreatment results in a heterologous desensitization in GOTO and a homologous desensitization in SK-N-DZ cells. Topics: Alprostadil; Cell Survival; Cholera Toxin; Colforsin; Cyclic AMP; Dinoprostone; Drug Resistance; Drug Screening Assays, Antitumor; Drug Synergism; Humans; Neuroblastoma; Prostaglandin D2; Prostaglandins; Prostaglandins A; Tumor Cells, Cultured | 1988 |
Tumor cell biotransformation products of prostaglandin A1 with growth inhibitory activity.
The growth inhibitory effect and the fate of prostaglandin A1 (10(-6) M) were followed in cultures of rat B104 neuroblastoma and C6 glioma cells. More than 40% and 85% of the drug were neither recognized by a prostaglandin A1 antiserum nor extracted from the acidified medium with ethyl acetate, after 6 h and 24 h-incubation, respectively. When the supernatant of cells cultured in the presence of prostaglandin A1 during 24 hours was transferred to other cells and used as culture medium, the same growth inhibitory effect as with prostaglandin A1 was observed even when no prostaglandin A1 was added. After extensive purification and reverse phase HPLC of supernatant, four peaks more polar than prostaglandin A1 were shown; two of them were still active as growth inhibitors. This biotransformation was not observed with normal cells like L 929 or chick embryo fibroblasts, for which prostaglandin A1 had no inhibitory effect. The identification of these metabolites will allow the study of the structure-activity relationship. Topics: Animals; Biotransformation; Cell Division; Cell Line; Chemical Phenomena; Chemistry; Chromatography; Culture Media; Glioma; Neuroblastoma; Prostaglandins A; Radioimmunoassay; Rats | 1986 |