Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Supernatant fluids of mitogen-activated human tonsil lymphocytes contain large amounts of a factor toxic to mouse L cells. This substance, with a m.w. of 80,000 +/- 5,000 daltons, is called alpha-lymphotoxin (alpha-LT), to differentiate it from another toxin elaborated by mitogen activated human blood lymphocytes, called beta-lymphotoxin (beta-LT), which differs from alpha-LT in size (45,000 +/- 5,000 daltons), antigenicity, and stability. Further purification of alpha-LT by sequential phosphocellulose and DEAE-cellulose chromatography and polyacrylamide gel electrophoresis (PAGE) identifies a series of cytotoxins differing in ion exchange characteristics and electrophoretic mobilities. The three PAGE fractions (PAGE Ia, Ib and II), recovered in 2, 4.6, and 21% yield from the starting serum-free culture supernatant, represent purifications of 24-, 24- and 1851-fold, respectively. Each cytotoxic fraction has a ribonuclease activity. Comparison of RNase and mouse L cell cytotoxic activities of the three alpha-LT fractions shows that both activities for all three fractions have a similar temperature stability pattern and that both are similarly inhibited by DNA, single strand forms better than double strands, by glycerol in 5 to 20% concentration, and by protein denaturing reagents. These observations suggest, but do not prove, that mouse L cell toxicity and RNase activity are mediated by the same substance, which appears to occur in multiple or isozymic forms.
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PMID:Regulatory factors produced by lymphocytes. I. The occurrence of multiple alpha-lymphotoxins associated with ribonuclease activity. 108 66

Alterations in the morphology and histochemistry of vascular endothelial cells (EC) have been repeatedly observed at sites of chronic inflammation and immune reactions. These changes, which are most prominent in the EC postcapillary venules present in areas with large lymphocytic infiltrates, include the acquisition of a columnar or cuboidal morphology, the development of ribonuclease-sensitive metachromasia, and an increase in intracellular organelles. Thus, EC at sites of inflammation appear to be activated and to demonstrate increased metabolic activity. This study reports that both tumor necrosis factor-alpha (TNF) and lymphotoxin (LT) can activate cultured human umbilical vein EC, as measured by: 1) increased adhesiveness for lymphocytes, 2) increased cell metabolism, as measured by RNA and protein synthesis, and 3) increased cell volume. Although gamma interferon (IFN-gamma) and interleukin-1 (IL-1) have been shown previously to stimulate EC adhesiveness for lymphocytes, these two cytokines had only marginal effects on EC RNA and protein synthesis, and both caused a decrease in EC volume. These findings suggest that TNF and LT play a role in the type of activation of EC in vivo that leads to the development of tall endothelium and increased lymphocyte emigration.
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PMID:Endothelial cell activation induced by tumor necrosis factor and lymphotoxin. 246 2

A nonspecific immunosuppressive factor present in malignant (ovarian carcinoma) ascites fluid has been purified by acid extraction from a high molecular weight (greater than 20000) complex followed by preparative isoelectric focusing on Bio-lyte media. It is an acidic protein (pI = 3.6) of mol. wt. 50000 to 52000 as estimated by gel filtration and composed of subunits of 25000 to 26000 estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, under reducing conditions. It inhibits the phytohemagglutinin-dependent mitogenic response of normal peripheral blood lymphocytes by 50% at 2 microgram/ml concentrations in vitro and suppresses 80% of the plaque-forming cell response to sheep erythrocytes at 100 microgram per mouse in vivo. Its chemical identity with any of the known plasma proteins has not been established. Its failure to stain with periodic acid Schiff's reagent indicates its minimal content of carbohydrates. It is susceptible to tryptic and pronase digestion but insensitive to deoxyribonuclease and ribonuclease digestion. A smaller suppressive factor identified in the same fluid appears to be a lymphotoxin; it differs from the acid-extracted nonspecific suppressive factor in its lack of susceptibility to trypsin.
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PMID:Purification and characterization of an immunosuppressive factor from ovarian cancer ascites fluid. 627 81

The effect of various treatments on the activity of anti-treponemal lymphotoxin (ATL) produced by lymphocytes of syphilitic rabbits was studied. Treponema pallidum-killing activity of ATL was slightly reduced after heating at 56 degrees C and completely abolished at 100 degrees C. The significant reduction of the activity was also obtained after exposure of ATL to acidic conditions (pH 1-5) at room temperature, or by treatment with papain and neuraminidase. Activity of ATL was completely resistant to deoxyribonuclease, ribonuclease and trypsin treatment. ATL was eluted from the Sephadex G-100 column together with hemoglobin, that suggested the apparent molecular weight of ATL of about 65,000. The active fraction from the Sephadex G-100 column was further fractionated on DEAE-Sephadex A-50. The activity of ATL was widely spread in the column eluate, indicating the charge heterogeneity. All these data indicate that ATL is a relatively low molecular weight protein. The sensitivity to neuraminidase and heterogeneity of charge suggest that it is a glycosylated protein.
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PMID:Characterization of anti-treponemal lymphotoxin from lymphocytes of syphilitic rabbits. 638 57

During the Spacelab Life Sciences-2 mission, rats were dissected in space and biosamples were returned to Earth for analysis. Immunologic studies addressed the kinetics of T lymphocyte proliferative responses, cytotoxic activity of natural killer cells, and cytokine production. Experiments were performed by using spleen and bone marrow of rats dissected before flight, during flight, immediately after landing of the space shuttle (R + 0), or 14 days after landing (R + 14), as well as those of respective control animals. Each group consisted of five male Sprague-Dawley rats. It was demonstrated that T lymphocyte activity of rats dissected in flight was significantly decreased compared with the controls. This was observed during 48-, 72-, and 96-h cultivation and stimulation with the following mitogenic stimuli: concanavalin A (Con A; 0.1, 1.0, and 10.0 mg/ml), phytohemagglutinin (PHA; 2.5 mg/ml), and interleukin-2 (IL-2; 1 U/ml). The cell proliferation rate in rats dissected immediately after landing did not decrease, whereas that in rats dissected at R + 14 increased. The activity of spleen natural killer cells was reduced in response to 51Cr-labeled target cells during flight (YAC-1 and K-562) and after flight (YAC-1). At R + 14, their activity returned to normal. Another technique employed to measure natural cytotoxicity, using [3H]uridine-labeled target cells and ribonuclease, did not reveal any differences between control and experimental groups. In bone marrow, the activity of natural killer cells did not vary significantly. The production of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, and TNF-beta in spleen cell cultures of the flight rats was reduced. At R + 0, IL-1 and TNF-beta levels remained lowered, whereas TNF-alpha was increased. At R + 0, interferon-alpha and interferon-gamma levels were diminished. In summary, cell-mediated immunity in rats was significantly suppressed during flight. The time course variation of immune parameters after flight suggests that the changes may truly indicate a response of the immune system to spaceflight conditions that could increase over time.
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PMID:Effect of SLS-2 spaceflight on immunologic parameters of rats. 882 61

RC-RNase purified from Rana catesbeiana (bullfrog) oocytes is a pyrimidine-guanine sequence-specific ribonuclease. RC-RNase is derived from the RNase superfamily genes exerting distinct ribonucleolytic activity and possesses cytotoxicity to tumor cells, but rarely to primary cells. In this study, we utilized RC-RNase to function with antiproliferative cytokines. The combination with TNF-alpha or TNF-beta would not aggravate cell death. However, the combination with IFN-gamma could induce synergistic cytotoxicity verified by XTT assays toward three hepatoma cell lines bearing different differentiation stages. The distinct cytotoxicity from RC-RNase or RC-RNase/IFN-gamma on different hepatoma cells was correlated with the differentiation extent but not the proliferation rate of the cells. Despite the synergistic cytotoxicity and severe mitochondrial disruptions in the RC-RNase/IFN-gamma-treated cells, we scarcely detected any significant feature of apoptosis or necrosis by FACS analysis on annexin-V/propidium iodide staining. The mechanisms of cell death triggered by RC-RNase or RC-RNase/IFN-gamma require further investigation.
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PMID:Synergistic cytotoxicity of Rana catesbeiana ribonuclease and IFN-gamma on hepatoma cells. 1116 59

In an attempt to analyze the cellular and molecular basis of the capacity of bone marrow stromal cells to support hematopoiesis in culture, we developed a series of murine stromal cell lines from a single long-term bone marrow culture (BMC). The cytokines produced by these cells were analyzed using immunohistochemical techniques, ribonuclease protection assays (RPA) and RT-PCR. We examined the capacity of these cloned cell lines to replace primary bone marrow-derived stromal cells in long-term bone marrow cultures (LT-BMC) and sought correlations between the capacity to support hematopoiesis in culture with the production of known cytokines. These immortalized lines replicate many of the functions of the hematopoietic microenvironment. They express cytokines known to play a role in hematopoiesis. All of the lines constitutively express mRNA for PBSF (SDF-1), macrophage colony-stimulating factor (M-CSF), stem cell factor (SCF), FLT-3, thrombopoietin (TPO), interleukin 7 (IL-7), leukemia inhibitory factor (LIF), tumor necrosis factor-beta (TNF-beta), and interferon-gamma (IFN-gamma). Most lines also express granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF. They vary in their expression of IL-6, tumor growth factor-beta1 (TGF-beta1), TGF-beta2, and TNF-alpha. Growing these lines in the presence of cytokines that influence hematopoiesis alters the levels of cytokine message. The most striking effects were produced by TNF-alpha. In addition to the cytokine mRNAs, the cell lines express factors associated with bone formation such as osteoblast-specific factor-2 (OSF-2) and bone morphogenetic protein-1 (BMP-1). They also express the neural cell-adhesion molecule neuropilin and neurotrophic factors including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Several of the lines can maintain hematopoiesis in culture, as measured by the continuous production of myeloid colony-forming cells (CFU-c), for months. This capacity to support hematopoiesis does not correlate with any pattern of cytokine expression. Several of these lines also support the growth of human hematopoietic cells, and human CFU-c can be detected in the cultures in which CD34(+) bone marrow cells (BMC) are cultured on murine stromal cells. No correlation between the production of any of the known cytokines and the ability to support murine hematopoiesis was detected. In addition, there was no correlation between the capacity to support murine hematopoiesis and the capacity to maintain human HSC. Despite repeated cloning, the lines remain heterogeneous and are capable of producing cells with the properties of fibroblasts, osteoblasts, adipocytes, and myoblasts. In addition to the cytokine mRNAs, the cell lines express factors associated with bone formation such as OSF-2 and BMP-1. They also express the neural cell-adhesion molecule neuropilin and neurotrophic factors including NGF and BDNF.
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PMID:Immortalized multipotential mesenchymal cells and the hematopoietic microenvironment. 1127 66

"Decoy" oligonucleotides can be used as gene-specific nuclear factor (NF-kappaB) inhibitors to regulate gene expression. We applied two different decoy oligonucleotides that contained the NF-kappaB binding consensus sequences present in the immunoglobulin G (IgG)-kappaB and Bcl-x promoter into 7-day-old (P7) rat lateral ventricles before hypoxia/ischemia (HI) and compared their effects on gene expression in hippocampi to saline-treated, scrambled decoy-treated, or untreated hippocampi exposed to HI. Left hippocampi were collected at 12 hr after HI. Electrophoretic mobility shift assays (EMSAs) showed that the two decoy treatments had different effects on NF-kappaB binding to the IgG-kappaB and Bcl-x promoter-specific consensus sequences, respectively. We assessed the decoys' effects on gene expression 12 hr after HI using ribonuclease protection assays (RPAs) and Affymetrix DNA microarrays. RPAs showed that both decoys significantly decreased interleukin (IL)-1alpha mRNA levels but had no impact on IL-1beta, IL-6, and IL-10 mRNA levels. IgG-kappaB decoys significantly decreased tumor necrosis factor (TNF)-alpha and TNF-beta mRNA levels compared to minimal changes after treatment with Bcl-x decoys. DNA microarray analyses showed that Bcl-x decoy treatment significantly decreased Bcl-x(L) mRNA levels. The decreased Bcl-x(L) mRNA levels after Bcl-x decoy treatment was confirmed by RPA analysis. DNA microarray data also indicated that several other genes were affected by both decoys. Our results suggest that different NF-kappaB decoy treatments could differentially regulate transcriptional responses to central nervous system trauma. Careful design of decoy sequences, however, is essential to acquire selective effects on cell death outcome.
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PMID:Effects of NF-kappaB oligonucleotide "decoys" on gene expression in P7 rat hippocampus after hypoxia/ischemia. 1519 44