Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of the neuroblastoma cell line SHSY5Y with nerve growth factor (NGF) resulted in limited neurite extension, but proliferation continued. However, SHSY5Y cells treated with NGF and a pulse of the DNA polymerase alpha and delta inhibitor aphidicolin showed dramatic neuronal differentiation. Few differentiated cells were observed immediately following the NGF-aphidicolin treatment; however, continued treatment of the cells with NGF in the ensuing week resulted in extension of long neurites (> 400 microns). Neurite extension was not observed for cells treated with aphidicolin alone. Hence, aphidicolin and NGF act synergistically to induce differentiation of SHSY5Y cells. If maintained in NGF, the differentiated cells were stable for at least 1 month and displayed many neuronal characteristics. They were mitotically inactive, and, in contrast to control or NGF-treated cells, the differentiated cells required NGF for survival. The cells expressed multiple microtubule-associated proteins (MAP), including MAP 1A, MAP 1B, and tau. There was expression of synaptic vesicle antigens synaptophysin and SV2, but not synapsin Ia/b or synapsin IIa/b. Both hydroxyurea and thymidine, which inhibit synthesis of nucleotides, act synergistically with NGF to induce differentiation of SHSY5Y cells. Since aphidicolin, hydroxyurea, and thymidine are chemically unrelated, we conclude that these drugs enhance NGF-induced differentiation by blocking cell proliferation and not through an unrelated side effect. The model suggested by these studies is that differentiation is triggered by two simultaneous signals: NGF and cessation of cell proliferation.
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PMID:Neuronal differentiation triggered by blocking cell proliferation. 141 12

Primary sympathetic neuronal cultures were maintained for up to 5 weeks after inoculation with herpes simplex virus (HSV) without evidence of viral infection. Treatment with acyclovir for the first 7 days after viral inoculation prevented lytic infections in 100% of the cultures and resulted in viral latency in 100% of the cultures; reactivation occurred as the result of nerve growth factor (NGF) deprivation. Treatment of the cultures with several different inhibitors of viral DNA polymerase (acyclovir, aphidicolin, and phosphonoacetic acid) for 7 days after viral inoculation did not prevent the establishment of latency, which suggests that viral DNA replication was not required. During the latent phase of the infection, viral antigens were not detected with HSV-specific immunohistochemistry. However, 24 h after NGF deprivation, viral antigens were detected in essentially all of the neurons, indicating that the majority of neurons harbored latent HSV. The establishment of latency was not strain or type specific since latency was established with HSV type 2 and four strains of HSV type 1 and reactivation occurred in response to NGF deprivation.
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PMID:Characterization of nerve growth factor-dependent herpes simplex virus latency in neurons in vitro. 282 4

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.
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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 aim of our study was to isolate novel gene(s) involved in cell differentiation and embryonic liver development. Mouse cded/lior was identified from subtraction hybridization of embryonic liver cDNA libraries as well as an adult mouse liver genomic DNA library. The full open reading frame of cded/lior encodes a 131-amino acid protein with 71.88% overall similarity to the PH domain of rat PLC-gamma1. A gapped search with the C-terminal region of CDED/LIOR revealed a 36-41% similarity to several proteins related to signal transduction and cell replication, such as ORC1 and KSR. Northern blot analysis of adult mouse tissues shows a strong 2.6-kb transcript restricted to heart and skeletal muscle. RT-PCR utilizing cded/lior-specific primers demonstrates cded/lior mRNAs in heart, brain, and liver tissue throughout mid-embryonic mouse gestation. cded/lior maps to the distal end of mouse Chromosome (Chr) 2. Analysis of the genomic structure for cded/lior demonstrated a single exon gene that is not an alternatively spliced isoform of PLC-gamma1. Analysis of the cded/lior promoter region revealed a high GC-content, high ratio of CpG/GpC, multiple GC-boxes, the lack of a TATA box, CTF/NFI element, and two MyoD-MCK binding sites. These characteristics are also found in several genes important in the regulation of cell growth or DNA synthesis, such as transforming growth factor-beta1, c-Ha-ras, nerve growth factor, epidermal growth factor receptor, and DNA polymerase beta. These results suggest that cded/lior is a mesoderm/muscle-specific transcript that may be involved in the mesodermal inductive and regulatory interactions required for liver formation and embryonic development.
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PMID:Genomic structure, chromosomal mapping, and muscle-specific expression of a PH domain-associated intronless gene, cded/lior. 989 36

Fomitellic acid (FA) A and B are specific inhibitors of DNA polymerase alpha and beta. They showed cytotoxicity against rat pheochromocytoma cells (PC-12 cells) in a concentration-dependent manner. However, after PC-12 cells were cultivated with low concentrations of FAs, the cells extended neurites in greater degree similar to the cells cultivated with nerve growth factor. Another DNA polymerase alpha inhibitor, aphidicolin, also induced neurite outgrowth. Furthermore, PC-12 cells were strongly immunostained with anti-alpha-tubulin or anti-tau antibody after the treatment with FAs. These results suggest that weak inhibition of DNA polymerase activity induces the neurite outgrowth in PC-12 cells.
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PMID:Differentiation of rat pheochromocytoma cells by fomitellic acids, specific DNA polymerase inhibitors. 1098 59

In tissue culture, rat pheochromocytoma (PC12) cells differentiated with nerve growth factor (NGF) cease division, extend neuritic processes and acquire many properties characteristic of neuronal cells. In previous work, we have shown that NGF-differentiated PC12 cells can survive infection with herpes simplex virus type 1 (HSV-1) and maintain the viral genome in a quiescent but reactivatable state. In this study, we report that uninfected NGF-differentiated PC12 cells uniformly and predictably detach from the culture flask substratum after approximately 7 weeks. Although uninfected cells were uniformly lost from the culture by 7 weeks, surprisingly HSV-1-infected cells survived beyond 10 weeks, the time limit of the study. The detachment of uninfected cells was not the result of cell death or apoptosis, as determined by viability assays performed on cells after detachment. Expression of the HSV-1 latency associated transcript (LAT) gene and virus replication was not necessary for the virus to suppress the 'detachment' phenomenon, since NGF-differentiated PC12 cells infected with either wild-type, DNA polymerase mutant or LAT null mutant virus survived in culture for similar lengths of time. Viral gene expression does appear to be necessary for the suppression, however, since cells infected with UV-inactivated virus were lost from culture with kinetics similar to those of uninfected cells. These findings indicate that de novo viral gene synthesis mediates changes to the host NGF-differentiated PC12 cells, which results in prevention of detachment.
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PMID:Herpes simplex virus type 1 infection prevents detachment of nerve growth factor-differentiated PC12 cells in culture. 1207 77