Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The injection of recombinant interleukin-1 (IL-1) into mice induced histidine decarboxylase (HDC) activity in the bone marrow, spleen, lung and liver and ornithine decarboxylase (ODC) activity in the spleen and liver. The ability of IL-1 to induce these responses was the most potent of the various cytokines tested. The induction of these responses by IL-1 seemed to be more rapid than that produced by a lipopolysaccharide. The potency of IL-1 alpha to induce both HDC and ODC activities was similar to that of IL-1 beta, and their combination did not potentiate the induction of these responses. In contrast, although the ability of recombinant tumor necrosis factor-alpha (TNF alpha) to induce these responses was less potent than that of IL-1 alpha or IL-1 beta, the combination of TNF alpha and IL-1 beta produced higher HDC and ODC activities in some tissues tested than those induced by the combination of IL-1 alpha and IL-1 beta. These results suggest that the syntheses of histamine and putrescine are regulated by IL-1 and/or TNF alpha in inflammatory or immune responses. Through these experiments, it was noticed that, in spite of a marked induction of HDC activity in the bone marrow, there was no detectable induction of ODC activity in this tissue. The meaning of HDC induction in the bone marrow is discussed.
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PMID:Induction of histidine and ornithine decarboxylase activities in mouse tissues by recombinant interleukin-1 and tumor necrosis factor. 278 63

Ornithine decarboxylase (ODC) activity was rapidly induced in the RAW264 macrophage-like cell line after treatment with bacterial lipopolysaccharide (LPS). ODC mRNA levels were determined by isolating cellular RNA, followed by Northern blot and dot blot analysis using a 32P-labeled cDNA probe. ODC mRNA levels increased within 1 hour of stimulation of RAW264 cells with 1.0 microgram/ml LPS. Transcription rate analysis on isolated nuclei indicated that an increase in transcription rate contributed to this increase in ODC mRNA. ODC mRNA levels continued to rise for 4 hours, peaking at eight times the basal level. ODC mRNA appeared as a single 2.2-kb band prior to stimulation. After stimulation, the 2.2-kb band intensified, and a second (2.7 kb) band was seen by Northern gel analysis. Similar induction was demonstrated when 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was used as the stimulus. The induction of ODC mRNA by either LPS or TPA was blocked by the addition of cycloheximide (25 micrograms/ml) or anisomycin (0.1 mM) to the cellular incubation mixture. This indicated that protein synthesis was required as a prerequisite to LPS or TPA induction of ODC mRNA. Experiments in which cycloheximide addition was delayed after LPS treatment indicated that some of the required protein synthesis occurred within the first 30 minutes and that complete expression of ODC mRNA was possible if protein synthesis continued for at least 2 hours before cycloheximide was added. Stimulation with 8-bromo-cAMP in addition to LPS has been shown to enhance the induction of ODC over that induced by LPS or TPA alone. It was not possible to block ODC mRNA induction with cycloheximide or anisomycin after treatment with the combined stimulus of LPS and cAMP or TPA and cAMP, indicating that protein synthesis was not required when cAMP was used as a coinducer. Thus, we have shown that in the same cell, ODC mRNA can be induced by two different pathways, one requiring protein synthesis and one not requiring protein synthesis.
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PMID:Rapid expression of ornithine decarboxylase mRNA in a macrophage-like cell line: cAMP repression of the requirement for prior protein synthesis. 283 24

Intraperitoneal (i.p.) and intravenous (i.v.) injection of human recombinant interleukin-1 beta (rIL-1 beta) in mice produced a 2-4 fold induction of ornithine decarboxylase (ODC) in liver and heart six hours after administration. Lymphoid organs (thymus and spleen) and brain did not respond to rIL-1 beta administration with significant increases in ODC. IL-1-induced responses in heart seemed not to be secondary to stress induced catecholamine release since the beta-adrenergic antagonist propranolol did not inhibit the induction of ODC produced by injection rIL-1 beta. Injection of 10 micrograms bacterial lipopolysaccharide (LPS), an inducer of IL-1 synthesis, exhibited a pattern of tissue responsiveness which was distinct from the responses elicited by rIL-1 beta, most notably a marked 5-fold induction of ODC in spleen. The differences in the responses of various organs to rIL-1 beta vs. LPS suggested that the in vivo effects of LPS may involve more than stimulation of the release of IL-1. The identification of heart as an IL-1 sensitive tissue merits further study to define the contribution of IL-1 to cardiac physiology and pathophysiology.
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PMID:Identification of some interleukin-1 (IL-1) sensitive organs in vivo using the induction of ornithine decarboxylase (ODC) following injection of recombinant IL-1 beta in mice. 350 8

Experiments were carried out to study the mechanism of the induction of ornithine decarboxylase (ODC) in mouse tissues by the injection of a lipopolysaccharide (LPS). In addition to LPS, various mitogenic substances, such as concanavalin A, pokeweed mitogen, polyI:polyC and a phorbol diester, induced ODC in the liver and the spleen of mice at 4.5 hr after injection. Non-mitogenic immuno-stimulants or inflammatory agents, such as zymosan, carrageenan, N-acetylmuramyl-L-alanyl-D-isoglutamine, glycogen, D-galactosamine and interferon, did not induce the enzyme. ODC induction by LPS in C3H/HeJ mice, the lymphocytes and/or macrophages of which are known to be less responsive to LPS, was much less than in C3H/He and ddI mice. ODC induction by LPS was suppressed by dexamethasone and cycloheximide. Actinomycin D did not suppress ODC induction by LPS but, rather, enhanced it. These results suggest that (1) lymphocytes and/or macrophages may participate in the induction of ODC by mitogenic substances as well as by LPS, (2) ODC may be induced by mitogenic substances without the synthesis of RNA, and (3) the translation of existing RNA may be accelerated by actinomycin D.
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PMID:Induction of ornithine decarboxylase in mouse tissues following the injection of mitogenic substances. Enhancement by actinomycin D. 674 56

The injection of Escherichia coli lipopolysaccharide (LPS) into mice produced simultaneous induction of histidine and ornithine decarboxylases in the liver, lung, spleen and kidney. The time courses of the changes in activities of the two enzymes were similar in all the tissues. After the injection, both activities increased within 1.5 hr, peaked at 4.5 hr and returned to the basal levels within 15 hr. The induction of these enzymes was very sensitive to this agent, i.e. as little as 1 microgram/kg of the E. coli lipopolysaccharide produced significant increases in these enzyme activities. An increase in the product amines, histamine and putrescine, followed the rise of enzyme activities. The levels of histamine changed more rapidly than those of putrescine. In spite of the increase in putrescine, there was no increase in spermidine and spermine. In the brain and thymus the LPS induced ornithine decarboxylase, but not histidine decarboxylase. In the blood, the histamine level increased without an increase in the activity of histidine decarboxylase. These results are discussed in relation to the actions of lipopolysaccharide. A simple method for the simultaneous assay of the activities of histidine and ornithine decarboxylases without using radioisotope substrates was used in this study.
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PMID:Simultaneous induction of histidine and ornithine decarboxylases and changes in their product amines following the injection of Escherichia coli lipopolysaccharide into mice. 704 56

To clarify the base of in vivo biological activities of peptidoglycans of Gram-positive bacteria, the effects of a polysaccharide peptide of Staphylococcus epidermidis peptidoglycan (SEPS) on the synthesis of histamine and putrescine in BALB/c mice were examined and compared with those of a lipopolysaccharide (LPS or endotoxin) of Gram-negative bacteria. Within a few hours after its injection into BALB/c mice, SEPS induced histidine decarboxylase (HDC), the enzyme forming histamine, in the liver, lung, spleen and bone marrow, and ornithine decarboxylase (ODC), the enzyme forming putrescine, in the tissues except for the lung. SEPS induced HDC activity even in mast cell-deficient mice and in nude mice. These effects of SEPS were essentially the same as those of LPS. However, the dosage of SEPS capable of inducing HDC and ODC was much higher (100 to 1,000 times) than that of LPS. We have reported that C3H/HeN mice are resistant to SEPS in producing acute arthritis, and their productions of IL-1 and prostaglandin E2 are less than BALB/c mice sensitive to producing acute arthritis. In the present study, it was also found that C3H/HeN mice were markedly resistant to SEPS in inducing HDC activity.
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PMID:Stimulation of the synthesis of histamine and putrescine in mice by a peptidoglycan of gram-positive bacteria. 807 26

Macrophage-like RAW 264 and H35 hepatoma cells grown under serum-free conditions exported putrescine and an unidentified diamine into the culture medium. Unlike putrescine, the unknown compound could be detected only extracellularly. Analyses of dansylated polyamine standards and mass spectroscopy confirmed that the unknown compound was cadaverine (1,5-diaminopentane). The cells were free of mycoplasma as evidenced by a negative result using a probe specific for prokaryotic rRNA. After prophylactic treatments with two different mycoplasmacidal agents, the cells continued to export cadaverine. Attempts to "infect" a noncadaverine-exporting cell line with culture medium and cell-free lysates proved unsuccessful, establishing that cadaverine was in fact a bona fide product of these mammalian cells. Cadaverine export by RAW 264 and H35 cells was stimulated by lipopolysaccharide and insulin, respectively. However, administration of exogenous ornithine caused cadaverine export to decrease significantly with concomitant increases in putrescine export. alpha-Difluoromethylornithine, a selective inhibitor of ornithine decarboxylase, inhibited both cadaverine and putrescine export. When cells were labeled with [3H]lysine, the great majority of the radioactivity recovered in exported polyamines was found in cadaverine. The cumulative data suggested that cadaverine formation may be caused by the action of intracellular ornithine decarboxylase upon lysine to produce cadaverine, which is then effluxed from the cell with a high degree of efficiency.
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PMID:Biosynthesis and selective export of 1,5-diaminopentane (cadaverine) in mycoplasma-free cultured mammalian cells. 812 59

Ceramide has emerged as a novel lipid mediator in cell growth and apoptosis. In difluoromethylornithine-resistant L1210 cells stimulated to growth from quiescence, the cell-permeant analogues of ceramide N-acetylsphingosine (C2-ceramide) and N-hexanoylsphingosine (C6-ceramide) inhibited the induction of ornithine decarboxylase (ODC) activity with IC50 of 8.3 and 1.5 microM respectively. This effect was strictly related to the ability to inhibit cell growth and [3H]thymidine incorporation. The suppression of cell growth was also associated with apoptosis. The addition of bacterial sphingomyelinase resulted in a significant, but limited, reduction of ODC induction and [3H]thymidine incorporation. Bacterial lipopolysaccharide, which may act as a ceramide analogue, also inhibited the induction of the enzyme. Moreover, C6-ceramide largely prevented the accumulation of ODC mRNA and its precursor, ODC heterogeneous nuclear RNA, that accompanied the induction of ODC activity. A slight increase in ODC turnover was also observed. The DNA-binding activity of some transcription factors known to bind and transactivate the ODC gene was investigated by gel mobility-shift assay under the same experimental conditions. However, only the binding of Myc/Max was negatively affected by the treatment with C6-ceramide. Furthermore, the amount of immunoreactive c-Myc, which increased after stimulation of the cells to growth, was strongly reduced by C6-ceramide. These results suggest that the inhibition of c-Myc and ODC expression may be early events in the response of leukaemia cells to ceramide.
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PMID:Inhibition of the expression of ornithine decarboxylase and c-Myc by cell-permeant ceramide in difluoromethylornithine-resistant leukaemia cells. 921 Apr 1

Tumor necrosis factor-alpha (TNF-alpha) induces a rapid increase in polymorphonuclear leukocyte (PMN) polyamine content which appears to be required for optimal priming of the respiratory burst. The objective of the present study was to determine whether inhibition of polyamine biosynthesis modifies PMN responses to lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte colony-stimulating factor (G-CSF). Treatment with alpha-difluoromethylornithine (DFMO), a selective inhibitor of the rate-limiting biosynthetic enzyme ornithine decarboxylase, produced dose-dependent inhibition of the respiratory burst in PMNs that were primed by these agents and subsequently activated by formyl-Met-Leu-Phe (fMLP). However, DFMO did not significantly inhibit fMLP-stimulated superoxide generation or alter the induction of PMN adhesion and interleukin-1 beta (IL-1 beta) mRNA expression by LPS or GM-CSF. Antagonism of priming by DFMO correlated with a dose-dependent attenuation of fMLP-induced intracellular Ca2+ mobilization (r > or = 0.96). Since Ca2+ plays an important role in modulating the respiratory burst in primed PMNs, this could, in part, account for the selective effects of DFMO.
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PMID:An inhibitor of ornithine decarboxylase antagonizes superoxide generation by primed human polymorphonuclear leukocytes. 936 91

The objective of this study was to elucidate the role and mechanism of nitric oxide (NO) synthase (NOS) in modulating the growth of the Caco-2 human colon carcinoma cell line. The two novel observations reported here are, first, that NG-hydroxy-L-arginine (NOHA) inhibits Caco-2 tumor cell proliferation, likely by inhibiting arginase activity, and, second, that NO causes cytostasis by mechanisms that might involve inhibition of ornithine decarboxylase (ODC) activity. Both arginase and ODC are enzymes involved in the conversion of arginine to polyamines required for cell proliferation. Cell growth was monitored by cell count, cell protein analysis, and DNA synthesis. NOHA (1-30 microM) and NO in the form of DETA/NO (1-30 microM) inhibited cell proliferation by 30-85%. The cytostatic effect of NOHA was prevented by addition of excess ornithine, putrescine, spermidine, or spermine to cell cultures, whereas the cytostatic effect of NO (DETA/NO) and alpha-difluoromethylornithine (ODC inhibitor) was unaffected by ornithine but was prevented by putrescine, spermidine, or spermine. The cytostatic effect of NOHA appeared to be independent of its conversion to NO, and the effect of NO appeared to be independent of cGMP. NOHA inhibited urea production by Caco-2 cells and inhibited arginase catalytic activity (85% at 3 microM), whereas NO (DEA/NO and SNAP) inhibited ODC activity (>/=60% at 30 microM) without affecting arginase activity. Coculture of Caco-2 cells with lipopolysaccharide/cytokine-activated rat aortic endothelial cells markedly slowed Caco-2 cell proliferation, and this was blocked by NOS inhibitors. These observations that NOHA and NO may inhibit sequential steps in the arginine-polyamine pathway suggest a novel biological role for NOS in the inhibition of cell proliferation of certain tumor cells and possibly other cell types.
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PMID:NG-hydroxy-L-arginine and nitric oxide inhibit Caco-2 tumor cell proliferation by distinct mechanisms. 975 58


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