Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was established as the constitutive and elicited human umbilical vein endothelial cell-derived eosinophil viability-sustaining factor. Stimulation of endothelium cell monolayers with IL-1 alpha (5 U/ml) increased the 48-h elaboration of GM-CSF from a mean of 3.2 to a mean of 8.2 pM (P less than 0.05). Dexamethasone (100 nM) decreased the constitutive GM-CSF elaboration by 49% (P less than 0.001) but did not diminish production by IL-1 alpha-stimulated endothelium. However, eosinophil viability decreased by 21% in dexamethasone-pretreated IL-1 alpha-stimulated endothelial cell-conditioned medium (P less than 0.05), which suggested viability antagonism by glucocorticoids. After 24 h of culture, eosinophil viability for replicate cells in enriched medium alone or with 1 pM GM-CSF decreased from means of 43 and 75% to means of 21 and 54%, respectively, when dexamethasone was included (P less than 0.05). However, 10 pM GM-CSF, IL-3, or IL-5 protected the cells against dexamethasone and against endonuclease-specific DNA fragmentation. In this model system of eosinophil-tissue interactions, dexamethasone prevents the endothelial cells from inducing a pathobiologic phenotypic change in the eosinophil by suppression of GM-CSF elaboration to concentrations that are not cytoprotective. Cytokine priming by GM-CSF, IL-3, or IL-5 may account for the differential responsiveness of select eosinophilic disorders to glucocorticoids.
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PMID:Eosinophil hematopoietins antagonize the programmed cell death of eosinophils. Cytokine and glucocorticoid effects on eosinophils maintained by endothelial cell-conditioned medium. 175 57

The IL3-dependent cell line FDCP-2 dies within 32 h of removal of IL3. Electron microscope studies indicate that 22 h after IL3 removal the nuclei are condensed, but the morphology of mitochondria and ribosomes is preserved. This pattern is characteristic of apoptosis. IL3 removal also results in the fragmentation of DNA into nucleosome-sized pieces, suggesting that an endonuclease is activated. The protein synthesis inhibitor, cycloheximide, enhances survival on IL3 removal, suggesting that death is an active process. The nuclease inhibitor, aurintricarboxylic acid, also enhances survival, suggesting a causal role for DNA fragmentation in apoptosis.
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PMID:IL3-dependent cells die by apoptosis on removal of their growth factor. 204 79

As demonstrated by long-range mapping of restriction endonuclease recognition sequences and genomic cloning, we found that the human genes encoding interleukin 3 (IL 3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) are tandemly arrayed on the long arm of chromosome 5, separated by 9 kilobases (kb) of DNA. This close physical linkage of genes with similar structure and biologic function suggests that these cytokines may have evolved from a common ancestral gene. This linkage in evolution of two relatively divergent genes further implies that some of the other lymphokine and cytokine genes that appear to share as much or more sequence similarity than do IL 3 and GM-CSF may be distantly related members of a cytokine gene family.
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PMID:The human genes for GM-CSF and IL 3 are closely linked in tandem on chromosome 5. 283 32

Murine bone marrow-derived hemopoietic cells, dependent on interleukin (IL)-3 for their growth in culture, undergo programmed cell death, or apoptosis, upon cytokine withdrawal. The topoisomerase II inhibitor etoposide causes a more rapid onset of apoptosis in the IL-3-dependent cell line BAF3, deprived of IL-3. This acceleration of apoptosis by etoposide is prevented by inhibitors of RNA and protein synthesis and by the nucleases inhibitor aurintricarboxylic acid. The presence of IL-3 or overexpression of the oncogene bcl-2 caused a marked delay in the induction of apoptosis by etoposide, acting in a cooperative manner. The time at which the apoptotic program is irreversible is close to the induction of endonuclease activity as indicated by the effect of the delayed addition of either IL-3 or aurintricarboxylic acid on the onset of apoptosis, suggesting the importance of endonuclease activation in the development of apoptosis in hemopoietic cells.
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PMID:Interleukin-3 and Bcl-2 cooperatively inhibit etoposide-induced apoptosis in a murine pre-B cell line. 751 Feb 34

DNA fragmentation in isolated nuclei from the murine IL3-dependent bone marrow cell line BAF3 could be stimulated either by decreasing pH below 6.5 or by adding microM calcium at neutral pH. An endonuclease which could also be stimulated either by a decrease in pH, to 6.5, or by the presence of microM calcium at neutral pH, was purified 10(4)-fold from nuclei of BAF3 cells. Digestion of DNA with the purified enzyme resulted in 5'-terminal hydroxyl and 3'-terminal phosphate ends. These characteristics are distinct from those described for other mammalian endonucleases. The possible role of this enzyme in genome digestion during apoptosis is discussed.
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PMID:An apoptotic endonuclease activated either by decreasing pH or by increasing calcium. 888 88

Efficient selection of the genetically modified cell population is a critical step to obtain the cells with desired properties. In this study, we propose an antigen-mediated genetically modified cell amplification (AMEGA) system employing an antibody/receptor chimera that triggers a growth signal in response to a non-toxic hapten dimer. An anti-fluorescein single-chain Fv fused to the extracellular D2 domain of erythropoietin receptor and transmembrane/intracellular domains of gp130 was expressed together with a model transgene, enhanced green fluorescent protein (EGFP) downstream of IRES sequence, by retroviral infection to IL-3-dependent Ba/F3 cells. Addition of fluorescein dimers connected by various oligo-DNA linkers induced selective growth of transfectants, thus leading to efficient expansion of EGFP-positive cell population. Also, digestion of the oligonucleotides by specific restriction endonuclease completely suppressed cell growth. Because these hapten dimers are not harmful for normal cells, the approach will be especially useful for reversible in vitro or in vivo expansion of genetically modified cell population employed for cell therapy and tissue engineering.
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PMID:Selection of genetically modified cell population using hapten-specific antibody/receptor chimera. 1501 36