Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following induction of differentiation by incubation with 1.25% dimethylsulfoxide (DMSO), cells of the HL60 promyelocytic leukaemia cell line acquire certain characteristics of the mature polymorphonuclear leucocyte (PMN) including the ability to produce oxygen radicals and to phagocytose opsonized bacteria. However, these cells are unable to fix 125I during phagocytosis and are only able to kill phagocytosed microorganisms (C. albicans and S. aureus) to a small degree compared to mature PMN. Further, release of myeloperoxidase (MPO) from cytoplasmic granules occurs to approximately 20% of control levels after 6 days culture with DMSO, and drops to negligible levels by 7 days. These data suggest an immature or inactive MPO/peroxide/halide killing system. Insensitivity to the cyclooxygenase pathway inhibitor indomethacin suggests that there may also be a defect in this pathway.
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PMID:Differentiated HL60 promyelocytic leukaemia cells have a deficient myeloperoxidase/halide killing system. 300 85

Streptoverticillium hadanonense KY11449 was found to produce a 12-lipoxygenase inhibitor MY3-469. The compound was purified by chromatography on Diaion HP-10, charcoal, Sephadex LH-20 and crystallization. The chemical structure of MY3-469 was determined to be 3-methoxytropolone on the basis of its physico-chemical properties. The half maximal inhibitory concentration (IC50) of MY3-469 against bovine platelet 12-lipoxygenase was 1.8 X 10(-6)M. The compound did not inhibit bovine platelet cyclooxygenase at 10(-3)M and showed weak inhibition (IC50 2.8 X 10(-4)) against 5-lipoxygenase of rat basophilic leukemia cells. The results indicate that MY3-469 is a potent and selective inhibitor of 12-lipoxygenase.
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PMID:Studies on lipoxygenase inhibitors. I. MY3-469 (3-methoxytropolone), a potent and selective inhibitor of 12-lipoxygenase, produced by Streptoverticillium hadanonense KY11449. 308 66

Pseudomonas methanica KY4634 was found to produce 5-lipoxygenase inhibitor designated KF8940, MY12-62a and MY12-62c. The inhibitors were purified by solvent extraction, silica gel column chromatography, reversed-phase low pressure liquid chromatography and crystallization. The chemical structures of KF8940, MY12-62a and MY12-62c were determined to be 2-n-heptyl-4-hydroxyquinoline-N-oxide, 2-n-heptyl-4-hydroxyquinoline and 3-n-heptyl-3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-dione, respectively, on the basis of their physico-chemical properties. Among them, KF8940 was the most potent inhibitor. The compound inhibited 5-lipoxygenase of rat basophilic leukemia cells in a dose-dependent manner and the half maximal inhibitory concentration (IC50) was 1.5 X 10(-7) M. At this concentration, KF8940 did not inhibit bovine platelet 12-lipoxygenase and cyclooxygenase, and the IC50 values for these enzyme were 3.5 X 10(-5) M and 1.7 X 10(-4) M, respectively. The results indicated that KF8940 is a potent and selective inhibitor of 5-lipoxygenase. The IC50 value of MY12-62c for 5-lipoxygenase was 1.9 X 10(-5) M and that of MY12-62a was 1.9 X 10(-5) M.
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PMID:Studies on lipoxygenase inhibitors. II. KF8940 (2-n-heptyl-4-hydroxyquinoline-N-oxide), a potent and selective inhibitor of 5-lipoxygenase, produced by Pseudomonas methanica. 309 34

The biochemical and biological profile of a topical anti-inflammatory agent, 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol (L-651,896 inhibited the 5-lipoxygenase of rat basophilic leukemia cells with an IC50 of 0.1 microM and leukotriene synthesis by human PMN and mouse macrophages with IC50 values of 0.4 and 0.1 microM respectively. L-651,896 also inhibited prostaglandin E2 synthesis by mouse peritoneal macrophages (IC50 = 1.1 microM). This compound inhibited ram seminal vesicle cyclooxygenase activity at considerably higher concentrations, and this effect was directly related to substrate concentration. When applied topically to the mouse ear, L-651,896 lowered elevated levels of leukotrienes associated with arachidonic acid-induced skin inflammation and delayed hypersensitivity induced by oxazolone. However, while L-651,896 inhibited the increased vascular permeability induced by arachidonic acid, it had no effect on the edema associated with the immune-based response to oxazolone in the same tissue. Thus, it is possible that leukotrienes may play a role in some but not all inflammatory responses.
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PMID:Biochemical and biological activities of 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol (L-651,896), a novel topical anti-inflammatory agent. 312 Jul 29

The use of rat basophilic leukemia (RBL-1) cell-line as a biosynthetic source of arachidonic acid metabolites has been previously described. We have developed a rapid and effective procedure for the extraction of lipoxygenase and cyclooxygenase products. The cells grown in spinner cultures were harvested and washed in phosphate buffer and stimulated by calcium ionophore A23187. The ethanolic extract of the cells was dried, dissolved in 20% methanol acidified with acetic acid and applied to octadecyl reversed phase cartridge (Backer C18). The cartridge was washed with 50% methanol (4 ml). Prostaglandins were eluted with 75% methanol (4 ml) and leukotrienes and related compounds with 100% methanol (4 ml). The identification of the fractions was carried out with pure standards. The recoveries of radiolabelled compounds ranged from 70% to 90%. This system can therefore accomplish an initial separation of major arachidonate metabolites and be applied in investigating metabolic pathways of arachidonic acid in different experimental conditions.
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PMID:Purification of arachidonic acid metabolites from cell cultures by octadecyl reversed phase cartridges. 393 Mar 18

Some eukaryotic cells in culture synthesize a variety of lipoxygenase and/or cyclooxygenase products when stimulated by appropriate agonists. Under normal nutritional conditions, these products are derived from the polyunsaturated fatty acid (PUFA) 5,8,11,14-eicosatetraenoic acid (ETA), arachidonic acid, which before metabolism must be liberated from cellular lipids by deesterification. If the cellular lipids are preloaded with 5,8,11,14,17-eicosapentaenoic acid (EPA) and cells are then stimulated to metabolize the PUFAs, levels of cyclooxygenase and lipoxygenase products synthesized are altered. Cyclooxygenase products decrease, while lipoxygenase products are not significantly affected and may even increase. The decrease in the production of cyclooxygenase products results from reduced utilization of the substrate (ETA). Decreased prostaglandin production by rat basophil leukemia-1 cells preloaded with EPA and radiolabeled with [3H]ETA and [14C]EPA can also be demonstrated by high-performance liquid chromatographic analyses of [3H]- and [14C] radiolabeled metabolites in culture fluids of cells stimulated to metabolize PUFA by the Ca2+ ionophore A23187.
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PMID:Eicosapentaenoic acid: its effects on arachidonic acid metabolism by cells in culture. 608 16

Previous studies in a line of rat basophilic leukemia (RBL 1) cells have indicated that the slow reacting substance (SRS) made during stimulation with the divalent cation ionophore, A23187, is derived from arachidonic acid (AA). In the present report, various inhibitors of AA metabolism were compared with regard to their effects on SRS formation and incorporation of radioactivity from [1-14C]-AA into known metabolites of the lipoxygenase and cyclooxygenase pathways. An apparently close parallel between lipoxygenase product formation and SRS synthesis is demonstrated. In addition, exogenous 5-hydroperoxy-eicosatetraenoic acid (5-HPETE) has been shown to markedly enhance SRS synthesis, even when A23187 is absent. The data provide very strong evidence that SRS is produced through the lipoxygenase pathway.
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PMID:Effect of the 5-hydroperoxide of eicosatetraenoic acid and inhibitors of the lipoxygenase pathway on the formation of slow reacting substance by rat basophilic leukemia cells; direct evidence that slow reacting substance is a product of the lipoxygenase pathway. 610 10

Treatment of murine NIH/MOL, C cells which are chronically infected with Moloney murine leukemia virus (MuLV), with mouse interferon (IFN), causes inhibition of extracellular MuLV production. We tested the effect of procaine, a drug that is known to expand cellular membranes and to increase their fluidity, on IFN-mediated inhibition of MuLV production. We observed that procaine did not alleviate this inhibition when IFN was present during procaine treatment. However, if IFN was removed from the culture medium before procaine treatment, the inhibition of MuLV production was partially reversed. We also observed that procaine treatment caused an increase in the amount of MuLV production by cells which had not been treated with IFN. Oxyphenylbutazone (OPB) is an inhibitor of cyclooxygenase, a key enzyme in prostaglandin biosynthesis. New synthesis of prostaglandins is thought to be needed for the antiviral actions of IFN. We observed that OPB did not prevent the antiretroviral action of IFN on NIH/MOL, C cells. OPB also failed to alleviate the IFN-mediated inhibition of replication of vesicular stomatitis virus either in NIH/MOL, C cells or in the L929 cells.
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PMID:Effects of procaine and oxyphenylbutazone on interferon-mediated inhibition of murine leukemia virus production. 619 28

HeLa cells incubated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and rat basophilic leukemia (RBL-1) cells incubated with calcium ionophore, showed increased levels of the protease plasminogen activator. These treatments have previously been shown to stimulate the cellular metabolism of arachidonic acid. The induction of plasminogen activator in both cell types was inhibited in a dose-dependent manner by 5,8,11,14-eicosatetraynoic acid and nordihydroguaiaretic acid, two compounds known to inhibit arachidonate metabolism via lipoxygenases. In contrast, indomethacin, which selectively inhibits arachidonate metabolism via cyclooxygenase, was inactive. The levels of four enzyme markers in HeLa cells were unchanged by treatment with TPA plus the lipoxygenase inhibitors, indicating that the inhibitors did not exert their effects on plasminogen activator via general cell toxicity. HeLa cells preincubated with [3H]arachidonate and subsequently challenged with TPA produced small amounts of material with the chromatographic mobilities and resistance to indomethacin expected of hydroxylated fatty acids derived via lipoxygenase. RBL-1 cells have been shown previously to produce leukotrienes and other lipoxygenase metabolites when treated with calcium ionophore. Plasminogen activator in HeLa cells was stimulated by up to 2.5-fold by incubation with 0.5-2 micrograms/ml 5-hydroxyeicosatetraenoic acid. Our results suggest that the induction of plasminogen activator in HeLa and RBL-1 cells is not mediated by prostaglandins or thromboxanes, but may be mediated or modulated by arachidonate metabolites derived via a lipoxygenase pathway.
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PMID:Induction of plasminogen activator by 12-O-tetradecanoylphorbol-13-acetate and calcium ionophore. Suppression by inhibitors of fatty acid lipoxygenase. 640 51

Arachidonic acid, metabolized by the enzyme contained in the cell-free homogenate of rat basophilic leukemia (RBL-1) cells, yields products of both the lipoxygenase and cyclooxygenase pathways. FPL 55712, the SRS-A antagonist, was found to inhibit the formation of lipoxygenase products, but not the cyclooxygenase products. Proxicromil was qualitatively similar, but markedly less potent. Disodium cromoglycate was inactive as an inhibitor of either metabolic pathway at concentrations up to 300 microM.
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PMID:Selective inhibition of the lipoxygenase metabolic pathway of arachidonic acid by the SRS-A antagonist, FPL 55712. 640 52


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