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

Simian immunodeficiency virus (SIV) was isolated from the total peripheral blood mononuclear cell population and the monocyte-macrophage adherent cell population of three seropositive green monkeys originating from Kenya. SIV from these African green monkeys (SIVagm) was isolated and continuously produced with the MOLT-4 clone 8 (M4C18) cell line but not with a variety of other cells including HUT-78, H9, CEM, MT-4, U937, and uncloned MOLT-4 cells. Once isolated, these SIVagm isolates were found to replicate efficiently in M4C18, SupT1, MT-4, U937, and Jurkat-T cells but much less efficiently if at all in HUT-78, H9, CEM, and MOLT-4 cells. The range of CD4+ cells fully permissive for replication of these SIVagm isolates thus differs markedly from that of previous SIV isolates from macaques (SIVmac). These SIVagm isolates had a morphogenesis and morphology like that of human immunodeficiency virus (HIV) and other SIV isolates. Antigens of SIVagm and SIVmac cross-reacted by comparative enzyme-linked immunosorbent assay only with reduced efficiency, and optimal results were obtained when homologous antibody and antigen were used. Western blotting (immunoblotting) of purified preparations of SIVagm isolate 385 (SIVagm385) revealed major viral proteins of 120, 27, and 16 kilodaltons (kDa). The presumed major core protein of 27 kDa cross-reacted antigenically with the corresponding proteins of SIVmac (28 kDa) and HIV-1 (24 kDa) by Western blotting. Hirt supernatant replicative-intermediate DNA prepared from cells freshly infected with SIVagm hybridized to SIVmac and HIV-2 DNA probes. Detection of cross-hybridizing DNA sequences, however, required very low stringency, and the restriction endonuclease fragmentation patterns of SIVagm were not similar to those of SIVmac and HIV-2. The nucleotide sequence of a portion of the pol gene of SIVagm385 revealed amino acid identities of 65% with SIVmac142, 64% with HIV-2ROD, and 56% with HIV-1BRU; SIVagm385 is thus related to but distinct from previously described primate lentiviruses SIVmac, HIV-1, and HIV-2. Precise information on the genetic makeup of these and other SIV isolates will possibly lead to better understanding of the history and evolution of these viruses and may provide insight into the origin of viruses that cause acquired immunodeficiency syndrome in humans.
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PMID:Simian immunodeficiency virus from African green monkeys. 317 40

HIVYU-6 and HIVYU-7 were isolated from an acquired immune deficiency syndrome patient (MK) and his asymptomatic sexual partner (MM), respectively. YU-6 readily infected not only peripheral lymphocytes from normal individuals but also human T-cell lines such as H9, HUT-78, MOLT-4 and MT-4; YU-7, on the other hand, could not infect H9 and MT-4 cells. Furthermore, although autologous serum failed to neutralize YU-6, it was neutralized by the heterologous serum from the partner. Restriction endonuclease analysis of YU-6 demonstrated that it was a mixture of viruses. We have isolated two clones from YU-6 (YU-6-a and YU-6-b) by a plaque assay method and showed that YU-6-a had one more KpnI site than YU-6-b. It was also evident that YU-7 derived from YU-6-a, but had already shifted genetically from YU-6-a. Transmission of human immunodeficiency virus through heterosexual contact and a possible genetic shift of YU-6-a, b and YU-7 from a common progenitor virus in vivo is discussed.
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PMID:Transmission and genetic shift of human immunodeficiency virus (HIV) in vivo. 350 21

When four human myelogenous leukemic cell lines (HL-60, ML-1, U-937, THP-1) were exposed to either ascorbic acid, hydrogen peroxide, etoposide, tumor necrosis factor, hyperthermia or UV irradiation, their growth inhibition and oligonucleosome-size DNA fragmentation were induced. Non-myelogenous leukemic cell lines (MOLT-4, K-562) were similarly sensitive to ascorbic acid and hydrogen peroxide, but relatively resistant to etoposide, TNF, hyperthermia and UV irradiation. Furthermore, these treatments except for UV irradiation, did not induce any apparent DNA fragmentation in MOLT-4 and K-562 cells. An autodigestion experiment revealed that all of these six cell lines contained divalent cation-independent endonuclease activity as a major endonuclease. The ability of this endonuclease to produce oligonucleosome-size DNA fragmentation was stimulated at acidic, but not at neutral pH. Since this enzyme activity was not detected in the lysosomal enzyme-free nuclei, prepared from all six cell lines, the cytoplasmic localization of this enzyme was suggested. The results suggest that the endonuclease activity might be differently regulated between myelogenous and non-myelogenous leukemic cell lines.
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PMID:Endonuclease activity and induction of DNA fragmentation in human myelogenous leukemic cell lines. 776 92

Certain anti-cancer agents are known to induce apoptosis in human tumour cells. However, these agents are intrinsically cytotoxic against cells of normal tissue origin, including myelocytes and immunocytes. Here we show that a naturally occurring flavone of citrus origin, tangeretin (5,6,7,8,4'-pentamethoxyflavone), induces apoptosis in human promyelocytic leukaemia HL-60 cells, whereas the flavone showed no cytotoxicity against human peripheral blood mononuclear cells (PBMCs). The growth of HL-60 cells in vitro assessed by [3H]thymidine incorporation or tetrazolium crystal formation was strongly suppressed in the presence of tangeretin; the IC50 values range between 0.062 and 0.173 microM. Apoptosis of HL-60 cells, assessed by cell morphology and DNA fragmentation, was demonstrated in the presence of > 2.7 microM tangeretin. Flow cytometric analysis of tangeretin-treated HL-60 cells also demonstrated apoptotic cells with low DNA content and showed a decrease of G1 cells and a concomitant increase of S and/or G2/M cells. Apoptosis was evident after 24 h of incubation with tangeretin, and the tangeretin effect as assessed by DNA fragmentation or growth inhibition was significantly attenuated in the presence of Zn2+, which is known to inhibit Ca(2+)-dependent endonuclease activity. Ca2+ and Mg2+, in contrast, promoted the effect of tangeretin. Cycloheximide significantly decreased the tangeretin effect on HL-60 cell growth, suggesting that protein synthesis is required for flavonoid-induced apoptosis. Tangeretin showed no cytotoxicity against either HL-60 cells or mitogen-activated PBMCs even at high concentration (27 microM) as determined by a dye exclusion test. Moreover, the flavonoid was less effective on growth of human T-lymphocytic leukaemia MOLT-4 cells or on blastogenesis of PBMCs. These results suggest that tangeretin inhibits growth of HL-60 cells in vitro, partially through induction of apoptosis, without causing serious side-effects on immune cells.
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PMID:Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. 851 48

Growth inhibitory activities of a novel 22-homo-23-norcholestane glycoside found in bulbs of Ornithogalum saundersiae were examined in vitro using human promyelocytic leukemia HL-60 cells, human T-lymphocytic leukemia MOLT-4 cells, and mitogen-stimulated human peripheral-blood mononuclear cells (PBMC). The growth of HL-60 cells and MOLT-4 cells was strongly suppressed in the presence of the glycoside; the IC50s of which were 21.0 and 18.0 nM, respectively. Suppressive effect of the glycoside on HL-60 cell growth appears to be mediated partially through induction of apoptosis which was demonstrated by the presence of DNA fragmentation of the leukemic cells. Flow cytometric analysis of glycoside-treated HL-60 cells also demonstrated apoptotic cells with low DNA content and showed a decrease of G0/G1 cells and a concomitant increase of S and/or G2M cells. The growth inhibiting effect of the glycoside on HL-60 cells was promoted by calcium and was inhibited in the presence of zinc, which support involvement of endonuclease activation in the glycoside-induced apoptosis. The glycoside also inhibited mitogen-stimulated blastogenesis of PBMC, the IC50 of which was 6.2 nM. These results provided the first evidence ever for the potent growth inhibitory activity of Ornithogalum glycoside on human leukemia cell lines and PBMC.
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PMID:Potent growth inhibitory activity of a novel Ornithogalum cholestane glycoside on human cells: induction of apoptosis in promyelocytic leukemia HL-60 cells. 863 26

The relationship between chromatin structure and endonuclease sensitivity was investigated. The cells used in this study were a) human myelogenous leukemic cell lines (HL-60, ML-I, U-937, THP-I) (Group I), which produced internucleosomal DNA cleavage, and b) human T-cell leukemia (MOLT-4), erythroleukemia (K562), glioblastoma (T98G, U87MG) and glioma (KG-1-C) cell lines (Group II), which produced no internucleosomal DNA cleavage, upon treatment with various apoptosis-inducing agents. When the nuclei, isolated from these cells were digested with micrococcal nuclease, chromatin DNA was cleaved into oligonucleosomal units. Although sensitivity to micrococcal nuclease considerably differed from cell to cell, Group I cells were generally more sensitive to micrococcal nuclease digestion than Group II cells. Similar sensitivity to DNase I was observed in both groups of cells. Acid-urea polyacrylamide gel electrophoresis of histone fractions from control and apoptosing HL-60 cells (induced either by hydrogen peroxide or UV irradiation) revealed no significant change in the relative composition of five major histones, indicating the absence of selective degradation of histone HI, but rather the nonspecific degradation of many nuclear proteins. These data suggest a difference in a chromatin structure between Group I and II cells, which might result in the selective production of internucleosomal DNA cleavage only in Group I cells.
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PMID:Chromatin structure and endonuclease sensitivity in human leukemic cell lines. 870 41

We compared two methods to stain apoptotic cells, one using terminal deoxynucleotidyl transferase (TDT), the other DNA polymerase I, using leukemia cell lines treated with anti-Fas monoclonal antibody (MAb). Both TDT and polymerase I strongly reacted with fragmented nuclei of apoptotic MOLT-16 and Jurkat cells, but only polymerase I strongly reacted with nonfragmented nuclei of early apoptotic cells. Anti-Fas MAb-treated MOLT-4 cells showed morphological changes corresponding to early apoptosis and were strongly positive for polymerase I only. MOLT-16 and Jurkat cells treated with anti-Fas MAb and inhibitors of endonuclease and poly(ADP-ribose) polymerase showed the morphology of early apoptosis but were not strongly stained by TDT. Because DNA polymerase I has nick-translation activity, it is possible that DNA polymerase I reaction is positive in early apoptotic cells by detecting single-strand DNA cleavage, which occurs before extensive oligonucleosomal DNA cleavage and late morphological changes of apoptosis in leukemia cell lines. Although TDT is widely used to stain apoptotic cells, DNA polymerase I may be more applicable in special cases of apoptosis, in which cells undergo single-strand rather than double-strand DNA breaks. However, the procedure has limitations, such as the necessity to use cell smears for comparison with the TDT reaction. (J Histochem Cytochem 46:85-90, 1998)
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PMID:Comparison of two methods of staining apoptotic cells of leukemia cell lines. Terminal deoxynucleotidyl transferase and DNA polymerase I reactions. 940 97

Programmed cell death (apoptosis), a form of cell death, described by Kerr and Wyllie some 20 years ago, has generated considerable interest in recent years. The mechanisms by which this mode of cell death (seen both in animal and plant cells), takes place have been examined in detail. Extracellular signals and intracellular events have been elaborated. Of interest to the clinician, is the concentrated effort to study pharmacological modulation of programmed cell death. The attempt to influence the natural phenomenon of programmed cell death stems from the fact that it is reduced (like in cancer) or increased (like in neurodegenerative diseases) in several clinical situations. Thus, chemicals that can modify programmed cell death are likely to be potentially useful drugs. From foxglove, which gave digitalis to the Pacific Yew from which came taxol, plants have been a source of research material for useful drugs. Recently, a variety of plant extracts have been investigated for their ability to influence the apoptotic process. This article discusses some of the interesting data. The ability of plants to influence programmed cell death in cancerous cells in an attempt to arrest their proliferation has been the topic of much research. Various cell-lines like HL60, human hepatocellular carcinoma cell line (KIM-1), a cholangiocarcinoma cell-line (KMC-1), B-cell hybridomas, U937 a monocytic cell-line, HeLa cells, human lymphoid leukemia (MOLT-4B) cells and K562 cells have been studied. The agents found to induce programmed cell death (measured either morphologically or flow cytometrically) included extracts of plants like mistletoe and Semicarpus anacardium. Isolated compounds like bryonolic acid (from Trichosanthes kirilowii var. Japonica, crocin (from saffron) and allicin (from Allium sativum) have also been found to induce programmed cell death and therefore arrest proliferation. Even Chinese herbal medicine "Sho-saiko-to" induces programmed cell death in selected cancerous cell lines. Of considerable interest is the finding that Panax ginseng prevents irradiation-induced programmed cell death in hair follicles, suggesting important therapeutic implications. Nutraceuticals (dietary plants) like soya bean, garlic, ginger, green tea, etc. which have been suggested, in epidemiological studies, to reduce the incidence of cancer may do so by inducing programmed cell death. Soy bean extracts have been shown to prevent development of diseases like polycystic kidneys, while Artemisia asiatica attenuates cerulein-induced pancreatitis in rats. Interestingly enough, a number of food items as well as herbal medicines have been reported to produce toxic effects by inducing programmed cell death. For example, programmed cell death in isolated rat hepatocytes has been implicated in the hepatitis induced by a herbal medicine containing diterpinoids from germander. Other studies suggest that rapid progression of the betel- and tobacco-related oral squamous cell carcinomas may be associated with a simultaneous involvement of p53 and c-myc leading to inhibition of programmed cell death. Several mechanisms have been identified to underlie the modulation of programmed cell death by plants including endonuclease activation, induction of p53, activation of caspase 3 protease via a Bcl-2-insensitive pathway, potentiate free-radical formation and accumulation of sphinganine. Programmed cell death is a highly conserved mechanism of self-defense, also found to occur in plants. Hence, it is natural to assume that chemicals must exist in them to regulate programmed cell death in them. Thus, plants are likely to prove to be important sources of agents that will modulate programmed cell death.
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PMID:Modulation of programmed cell death by medicinal plants. 1072 85

Diethyldithiocarbamate (DDTC) has been shown to induce cytotoxicity in several different systems. We examined whether the DDTC-induced cytotoxicity was via apoptosis, or in relation to intracellular glutathione (GSH) in various murine and human leukemia cell lines. The cells most sensitive to DDTC-induced cytotoxicity were P388 lymphoid neoplasma cells and NALM-6, a B cell line of acute lymphocytic leukemia (ALL). The next level of susceptible cells included J774.1, having a macrophage function, HL-60 premyelocytic leukemia cells, MOLT-4, an acute lymphoblastic leukemia cell, and Jurkat, a T-cell leukemia. U937 (expressing many monocyte-like characteristics), K562 erythroleukemia and K562/DXR (a multidrug-resistant clone derived from K562) were almost unaffected by DDTC. P388 was also highly susceptible to H(2)O(2), a most useful exogenous reactive oxygen species generator, and was lower in intracellular total GSH content than other leukemia cells. DDTC-induced cytotoxicity was closely related to intracellular GSH, but the level of cellular GSH did not always correlate with H(2)O(2)-induced cytotoxicity in this experiment. K562 had a higher intracellular total GSH content and showed lower susceptibility to DDTC and H(2)O(2), but with the combination of DDTC and DL-buthionine-(S,R)-sulfoximine (BSO), cytotoxicity increased significantly. The ratio of GSH/GSSG in P388 was reduced by DDTC or H(2)O(2). H(2)O(2)-induced cytotoxicity was completely blocked by catalase (CAT), while it was enhanced by superoxide dismutase (SOD). CAT or SOD did not affect DDTC-induced cytotoxicity. N-Acetylcysteine (NAC: 1 mM), a vanguard substance of GSH, and aurintricarboxylic acid (ATA: 100 microM), an endonuclease inhibitor, ameliorated DDTC-induced cytotoxicity and apoptosis. In conclusion, we suggest that DDTC-induced cytotoxicity was via an oxidative shift in the intracellular redox state, and accompanied the activation of endonuclease through apoptosis in leukemia cell lines.
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PMID:Diethyldithiocarbamate-induced cytotoxicity and apoptosis in leukemia cell lines. 1284 19