Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and two neural cell lines, mouse neuroblastoma (N1E-115) and rat glioma (C6-BU-1), was investigated. N1E-115 cells were permissive to both types of HSV. In C6-BU-1 cells, on the other hand, all the HSV-1 strains tested so far showed persistent infection, and the infectious virus of HSV-2 strains disappeared spontaneously. The HSV-2-infected C6-BU-1 cells were positive for HSV-2-specific DNA sequences, virus-specific RNA, HSV-2-specific antigens and thymidine kinase activity, when no infectious virus was detected. The HSV-2 was reactivated from those C6-BU-1 cells by superinfection with murine cytomegalovirus (MCMV), but not with UV-irradiated MCMV or human cytomegalovirus. The reactivated HSV-2 was identical to the parental virus, when examined by restriction endonuclease cleavage analysis.
 ...
PMID:Interaction of herpes simplex virus type 2 with a rat glioma cell line. 285 Apr 49

Human SY5Y neuroblastoma cells which were differentiated in culture by treatment with 7S murine nerve growth factor for 5 weeks and selection with aphidicolin (L. Jensen, Dev. Biol. 120:56-64, 1987) demonstrated a considerably slower rate of removal of DNA adducts of benzo[a]pyrene, benzo[a]pyrenediolepoxide, and N7-methylguanine than did undifferentiated mitotic cells. A dramatic decline in unscheduled DNA synthesis induced by UV radiation was similarly observed. DNA polymerase beta and uracil DNA glycosylase were unchanged after differentiation, DNA polymerase alpha and DNA methylase decreased roughly threefold, and total apurinic-apyrimidinic endonuclease activity increased roughly threefold after treatment.
 ...
PMID:A reduced rate of bulky DNA adduct removal is coincident with differentiation of human neuroblastoma cells induced by nerve growth factor. 314 94

The mechanism of N6,O2'-dibutyryl adenosine 3':5'-monophosphate (Bt2cAMP) induction of pro-vasoactive intestinal polypeptide (VIP)/PHM-27 biosynthesis was investigated in human neuroblastoma cells in culture. When neuroblastoma cells were grown for 48 h in the presence of 1 mM Bt2cAMP, the synthesis of pro-VIP/PHM-27 was stimulated 11-fold. The amount of prepro-VIP/PHM-27 mRNA determined both by hybridization with cloned prepro-VIP/PHM-27 cDNA and a reticulocyte cell-free translation assay was also increased 11-fold in the Bt2cAMP-induced cells. Transcription of prepro-VIP/PHM-27 mRNA in isolated nuclei was observed in induced cells, but not in uninduced cells. Blot hybridization with prepro-VIP/PHM-27 cDNA of total nuclear RNA isolated from neuroblastoma cells revealed an RNA species corresponding to mature prepro-VIP/PHM-27 mRNA, and the amount of the RNA was markedly increased in the induced cells. The quantity of VIP/PHM-27 gene in the DNA of neuroblastoma cells was analyzed after hydrolysis with a restriction endonuclease, EcoRI. However, VIP/PHM-27 gene was not amplified in the induced cells. These results indicate that Bt2cAMP-induced pro-VIP/PHM-27 synthesis is achieved by enhancing the transcription rate of prepro-VIP/PHM-27 mRNA.
 ...
PMID:Cyclic AMP regulation of pro-vasoactive intestinal polypeptide/PHM-27 synthesis in human neuroblastoma cells. 608 27

The effects of ultraviolet (U.V.) radiation were studied on a cloned line of human neuroblastoma cells in proliferative and differentiated growth modes, the latter being induced by serum deprivation. The neuroblastoma cells were found to be unusually sensitive in comparison with HeLa cells when survival was measured by colony formation in soft agar, the differentiated mode being the most sensitive. Ultraviolet radiation sensitivity was associated with very low DNA repair capacity as measured by DNA repair synthesis and by removal of M. luteus endonuclease-sensitive sites from irradiated DNA. The greater sensitivity of the differentiated cells appeared to be related to a greater degree of DNA damage at a given U.V. dose, resulting from altered cell geometry in the growth mode. The neuroblastoma cells showed little or no post-irradiation inhibition of DNA replication at low U.V. doses, suggesting that it is the repair process rather than the DNA damage which is responsible for inhibiting replication.
 ...
PMID:Ultraviolet radiation sensitivity of proliferating and differentiated human neuroblastoma cells. 698 Feb 2

The patterns of cell death induced by the cholinergic neurotoxin ethylcholine aziridinium have been investigated in vitro and in vivo. In vitro, the drug induced apoptosis both in neuronal SK-N-MC cells (human neuroblastoma cells) and in non-neuronal 293 cells (a human embryonic kidney cell line). Apoptosis was developed maximally between 15 and 24 h of exposure to ethylcholine aziridinium (100 microM). At the ultrastructural level apoptotic cells were characterized by condensation and margination of nuclear chromatin, fragmentation of nuclei and the formation of apoptotic bodies. Inhibition of endonuclease by zinc almost completely prevented the occurrence of apoptosis. The free radical scavenger Tempol effectively inhibited ethylcholine aziridinium-induced apoptosis by 78.6 +/- 10.3% (n=4), whereas cycloheximide and actinomycin D were only partially effective. In vivo, following injection of ethylcholine aziridinium (2 nmol) into the lateral ventricle of rat brain a high incidence of apoptotic cells as verified by in situ tailing was visible in the periventricular tissue. Neurons as well as glia were affected by the neurotoxin. The number of apoptotic cells peaked two to three days after injection of ethylcholine aziridinium and declined thereafter. Up to one week after ethylcholine aziridinium no signs for the induction of apoptosis in the medial septal nucleus were found. This study provides clear evidence that a neurotoxic compound that induces programmed cell death in vitro is likely to have the same capacity in vivo. Yet, in the case of ethylcholine aziridinium, both the in vitro and the in vivo induction of programmed cell death appears to be an additional feature of ethylcholine aziridinium, which may be independent of the well-established degenerative effect of ethylcholine aziridinium on the cholinergic septohippocampal pathway. The present data indicate that ethylcholine aziridinium provides a useful tool to study molecular mechanisms of neuronal apoptosis.
 ...
PMID:Induction of apoptosis in vitro and in vivo by the cholinergic neurotoxin ethylcholine aziridinium. 920 Jul 36

Thapsigargin, a specific inhibitor of the endoplasmic reticular Ca(2+)-ATPase, has been used previously to mobilize calcium release from intracellular calcium stores. We now show that thapsigargin (1-10 microM) induces apoptosis in a neuroblastoma cell line (SH-SY5Y) and in fetal rat cerebrocortical cultures. Cell death measured by lactate dehydrogenase release was observed 24-48 hours after treatment with thapsigargin. In both cases, DNA extracts from thapsigargin treated cells showed laddering, typical of endonuclease-mediated internucleosomal cleavages. The presence of DNA fragments was also confirmed by an ELISA designed for detecting nucleosomes in apoptotic cells. Cycloheximide reduced the extent of DNA fragmentation and injury in thapsigargin-treated cells. Dantrolene, an inhibitor of calcium release from intracellular stores partially abolished the effect of thapsigargin, suggesting that the initial Ca2+ rise may be the signalling event in this apoptotic cell death pathway. We propose that thapsigargin-induced cell death in cultured neuronal cells may be a useful system to study the molecular and genetic events involved in apoptosis.
 ...
PMID:Thapsigargin induces apoptosis in SH-SY5Y neuroblastoma cells and cerebrocortical cultures. 931 98

Caspase-activated DNase is responsible for the oligonucleosomal DNA degradation during apoptosis. DNA degradation is thought to be important for multicellular organisms to prevent oncogenic transformation or as a mechanism of viral defense. It has been reported that certain cells, including some neuroblastoma cell lines such as IMR-5, enter apoptosis without digesting DNA in such a way. We have analyzed the causes for the absence of DNA laddering in staurosporine-treated IMR-5 cells, and we have found that most of the molecular mechanisms controlling apoptosis are well preserved in this cell line. These include degradation of substrates for caspases, blockade of cell death by antiapoptotic genes such as Bcl-2 or Bcl-X(L), or normal levels and adequate activation of caspase-3. Moreover, these cells display normal levels of caspase-activated DNase and its inhibitory protein, inhibitor of caspase-activated DNase, and their cDNA sequences are identical to those reported previously. Nevertheless, IMR-5 cells lose caspase-activated DNase during apoptosis and recover their ability to degrade DNA when human recombinant caspase-activated DNase is overexpressed. Our results lead to the conclusion that caspase-activated DNase is processed during apoptosis of IMR-5 cells, making these cells a good model to study the relevance of this endonuclease in physiological or pathological conditions.
 ...
PMID:The absence of oligonucleosomal DNA fragmentation during apoptosis of IMR-5 neuroblastoma cells: disappearance of the caspase-activated DNase. 1129 34

Internucleosomal DNA fragmentation is an apoptotic event that depends on the activity of different nucleases. Among them, the DNA fragmentation factor B, better known as caspase-activated DNase (CAD), is mainly responsible for this DNA fragmentation in dying cells. CAD is an endonuclease that is chaperoned and inhibited by inhibitor of CAD (ICAD). Activation of CAD needs the cleavage of ICAD by activated caspase-3. During the characterization of the staurosporine-induced apoptotic process in human neuroblastoma cell lines, we have found three novel splice variants of CAD. In all three messengers, the open reading frame is truncated after the second exon of the CAD gene. This truncated open reading frame codifies the CAD protein amino terminal part corresponding to the cell death-inducing DFF45-like effector-N (CIDE-N) domain. We have detected these splicing variants in human tissues and in peripheral white blood cells from 10 unrelated individuals, and their products have been showed to be expressed in certain mouse tissues. We demonstrate that these truncated forms of CAD are soluble proteins that interact with ICAD. We also provided evidences that these CIDE-N forms of CAD promote apoptosis in a caspase-dependent manner.
 ...
PMID:Characterization of splice variants of human caspase-activated DNase with CIDE-N structure and function. 1514 1

Redox factor-1 (Ref-1), also known as HAP1, APE or APEX, is a multifunctional protein that regulates gene transcription as well as the response to oxidative stress. By interacting with transcription factors such as AP-1, NF-kappaB and p53, and directly participating in the cleavage of apurininic/apyrimidinic DNA lesions, Ref-1 plays crucial roles in both cell death signaling pathways and DNA repair, respectively. Oxidative stress induced by aggregated beta-amyloid (Abeta) peptide, altered DNA repair and transcriptional activation of cell death pathways have been implicated in the pathophysiology of Alzheimer's disease (AD). Here we show that varying concentrations of Abeta(1-42) differentially regulate Ref-1 expression, Ref-1 function and neuronal survival in vitro. Abeta (5.0 muM) caused a relatively rapid decrease in Ref-1 expression and activity associated with extensive DNA damage and neuronal degeneration. In contrast, Ref-1 induction occurred in cells exposed to Abeta (1.0 muM) without significant neuronal cell death. Abeta-induced attenuation of Ref-1 expression and endonuclease activity, and neuronal cell death were prevented by the anti-oxidant, catalase. Similar differential effects on Ref-1 expression and cell viability were observed in N2A neuroblastoma cells treated with either high or low dose hydrogen peroxide. These findings demonstrate the differential regulation of Ref-1 expression by varying degrees of oxidative stress. Parallels between the Ref-1 response to Abeta and H(2)O(2) suggest similarities between DNA repair pathways activated by different inducers of oxidative stress. In AD brain, colocalization of Ref-1 and Abeta the absence of significant DNA damage are consistent with the cell culture results and suggests that Ref-1 may play a more neuroprotective role under these conditions. Modulation of Ref-1 expression and activity by local variations in Abeta concentration may be an important determinant of neuronal vulnerability to oxidative stress in AD.
 ...
PMID:Differential Expression of Redox Factor-1 Associated with Beta-Amyloid-Mediated Neurotoxicity. 1989 78

Apoptotic cell death is characterized by nuclear fragmentation and oligonucleosomal DNA degradation, mediated by the caspase-dependent specific activation of DFF40/CAD endonuclease. Here, we describe how, upon apoptotic stimuli, SK-N-AS human neuroblastoma-derived cells show apoptotic nuclear morphology without displaying concomitant internucleosomal DNA fragmentation. Cytotoxicity afforded after staurosporine treatment is comparable with that obtained in SH-SY5Y cells, which exhibit a complete apoptotic phenotype. SK-N-AS cell death is a caspase-dependent process that can be impaired by the pan-caspase inhibitor q-VD-OPh. The endogenous inhibitor of DFF40/CAD, ICAD, is correctly processed, and dff40/cad cDNA sequence does not reveal mutations altering its amino acid composition. Biochemical approaches show that both SH-SY5Y and SK-N-AS resting cells express comparable levels of DFF40/CAD. However, the endonuclease is poorly expressed in the cytosolic fraction of healthy SK-N-AS cells. Despite this differential subcellular distribution of DFF40/CAD, we find no differences in the subcellular localization of both pro-caspase-3 and ICAD between the analyzed cell lines. After staurosporine treatment, the preferential processing of ICAD in the cytosolic fraction allows the translocation of DFF40/CAD from this fraction to a chromatin-enriched one. Therefore, the low levels of cytosolic DFF40/CAD detected in SK-N-AS cells determine the absence of DNA laddering after staurosporine treatment. In these cells DFF40/CAD cytosolic levels can be restored by the overexpression of their own endonuclease, which is sufficient to make them proficient at degrading their chromatin into oligonucleosome-size fragments after staurosporine treatment. Altogether, the cytosolic levels of DFF40/CAD are determinants in achieving a complete apoptotic phenotype, including oligonucleosomal DNA degradation.
 ...
PMID:Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40/CAD endonuclease. 2225 44


1 2 Next >>