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 effect of c-AMP, c-GMP and both substances together on (3H)-thymidine incorporation into nuclear DNA was investigated using spleen cells of normal and athymic nude mice. c-GMP induces DNA synthesis in both normal and nude spleen cell populations. c-AMP inhibited the stimulatory activity of c-GMP as well as the phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) response of spleen cells. The inhibitory activity of c-AMP on the PHA and LPS responses can be reversed by c-GMP. The possible role of cyclic nucleotides in the regulation of cell proliferation and of the immune response is discussed.
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PMID:The antagonistic action of cyclic GMP and cyclic AMP on proliferation of B and T lymphocytes. 16 87

The addition of cholinergic agents and cyclic 3'5'-guanosine monophosphate (cGMP) to polymorphonuclear leukocytes in vitro from a patient with Chediak-Higashi syndrome corrected the impaired release of the lysosomal enzyme, beta-glucuronidase, to normal. Coinciding with the improvement in degranulation, the bactericidal capacity was enhanced to normal. Similar concentrations of cholinergic agents potentiated chemotaxis to control values. On the other hand, the phagocytic rate of lipopolysaccharide-coated paraffin-oil droplets was not altered by the cholinergic agents. The improvement in Chediak-Higashi syndrome polymorphonuclear leukocyte function by the addition of cholinergic agents and dibutyryl cGMP suggested disturbed intracellular cyclic nucleotide levels.
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PMID:Improvement of Chediak-Higashi leukocyte function by cyclic guanosine monophosphate. 18 66

1. The aim of this investigation was to study the relationship between contractile responsiveness, activation of the L-arginine pathway and tissue levels of guanosine 3':5'cyclic monophosphate (cylic GMP) in aortic rings removed from rats 4 h after intraperitoneal administration of bacterial endotoxin (E. coli. lipopolysaccharide, LPS, 20 mg kg-1). 2. LPS-treatment resulted in a reduction of the sensitivity and maximal contractile response to noradrenaline (NA). 3. Depression of the maximal contractile response was restored to control by 6-anilo-5,8-quinolinedione (LY 83583, 10 microM), which prevents activation of soluble guanylate cyclase. 4. Cyclic GMP levels in tissue from LPS-treated rats were 2 fold greater than cyclic GMP levels detected in tissue from control (saline-treated) rats. The LPS-induced increase in cyclic GMP content was observed both in the presence and absence of functional endothelium. 5. Addition of L-arginine 1 mM) to maximally contracted aortic rings produced significantly relaxation of rings from LPS-treated rats but not rings from control animals. In the LPS-treated group, addition of L-arginine was also associated with a significant increase in cyclic GMP content. L-Arginine had no effect on the cyclic GMP content of control rings. D-Arginine (1 mM) was without effect. 6. In rings from LPS-treated rats, NG-nitro-L-arginine methyl ester (L-NAME, 300 microM), an inhibitor of nitric oxide (NO) production, increased the contractile response to NA and prevented the LPS-induced increase in cyclic GMP content. In control rings, L-NAME increased the NA sensitivity only when the endothelium remained intact and reduced the cyclic GMP content of these rings to that of control endothelium-denuded rings. 7. These results demonstrate that LPS-induced hyporeactivity to NA occurs secondarily to activation of the L-arginine pathway and subsequent activation of soluble guanylate cyclase in vascular tissue. In addition they suggest that LPS induces the production of an NO-like relaxing factor in non-endothelial cells.
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PMID:Evidence that an L-arginine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin. 167 81

Stimulant action of the mitogenic polyanion, polyacrylic acid (PAA) was investigated in mouse lymphocyte culture in vitro. B cell division was induced by "impulsive" PAA treatment. Shortly after PAA treatment the activity of the membrane enzymes, adenylate and guanylate cyclases, was assayed according to the changes in the concentration of cAMP and cGMP. The effect of PAA on the time course of cAMP and cGMP in lymphocytes was compared to the effect of B cell mitogen of other chemical nature--bacterial lipopolysaccharide (LPS). PAA was demonstrated to produce no effect on the activity of membrane cyclase enzymes. On the contrary, following LPS addition guanylate cyclase in the lymphocyte membrane was activated within the first 5-10 minutes. Later on (after 2h) the cells activated with LPS showed an increase in adenylate cyclase activity. By the 12th-24th hour the concentration of cAMP in the LPS-stimulated cells reached 250% of the control level. The differences are discussed between the mitogenic polyanion (PAA) and the lipid-modifying mitogen (LPS) in the molecular mechanisms by which the lymphocyte responses are activated.
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PMID:[Analysis of the cyclase enzyme activity of the cell membrane following lymphocyte stimulation with a mitogenic polyanion]. 614 37

The effect of dibutyryl cyclic guanosine monophosphate (dbc-GMP) on butylated hydroxyanisole (BHA)-induced suppression of the primary in vitro thymus-dependent antibody response of BDF1 mouse spleen cultures was studied. When added at 0 hr relative to antigen addition, 1 mg of dbc-GMP (8 mM) restored by greater than 70% the BHA-inhibited primary immunoglobulin (Ig)M plaque-forming cell (PFC) response to sheep erythrocytes (SRBC). The suppression was not reversed by the addition of 50 microgram of dibutryl cyclic adenosine monophosphate (dbc-AMP), which is known to reverse suppressor T-cell activity. The addition of 10 mM extracellular calcium (Ca2+) at the same time as antigen to BHA-inhibited cultures resulted in more than 80% restoration of the anti-SRBC PFC response. Quantitation of c-GMP by radioimmunoassay demonstrated that BHA lowered by 58% the c-GMP content of splenic lymphocytes and abrogated the ability of lipopolysaccharide of E. coli (LPS) to elevate c-GMP levels in splenic lymphocytes. The data suggest that BHA exerts its immunosuppressive effect on the primary in vitro antibody response by inhibiting guanylate cyclase activity and effectively lowering c-GMP levels; exogenous dbc-GMP and Ca2+ can freely reverse the immunosuppressive effect of BHA.
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PMID:Restoration by cyclic guanosine monophosphate and extracellular calcium of butylated hydroxyanisole-suppressed primary murine thymus-dependent antibody response. 627 34

The present study has examined whether epithelial cells could be a source of the inducible form of nitric oxide synthase (iNOS) in the colon of rats challenged with E. coli lipopolysaccharide and whether such excessive endogenous nitric oxide (NO) or exogenous NO released from NO donors could affect their viability. Epithelial cells were isolated from rat colon, and cell viability was determined by trypan blue exclusion. The appearance of a calcium-independent iNOS determined by the conversion of radiolabeled L-arginine to citrulline was observed in cells harvested from lipoplysaccharide (3 mg/kg for 4 hr)-treated rats, with a 10-fold increase in total NOS activity compared with control. This was accompanied by a 3-fold decrease in epithelial cell viability. Levels of iNOS and of cellular injury were not significantly affected in rats made neutropenic by the administration of antineutrophil serum. Induction of NOS was also associated with an increase in epithelial cyclic guanylate monophosphate levels. Both iNOS activity and cell injury were inhibited by in vivo pretreatment with dexamethasone (1 mg/kg i.v., for 4 hr) or the NOS inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg s.c.) in a dose that itself reduced viability. The incubation of epithelial cells with the NO donors, nitroprusside, S-nitroso-N-acetyl penicillamine or S-nitroso-N-glutathione (0.1-1 mM) produced concentration-dependent cytotoxicity. These findings indicate that the induction of NOS in colonic epithelial cells is not dependent upon infiltration of neutrophils and is accompanied by a reduction in cellular viability, an effect mimicked in vitro by NO donors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide synthase activity, viability and cyclic GMP levels in rat colonic epithelial cells: effect of endotoxin challenge. 752 55

Marked differences in induced nitric oxide (NO) synthesis occur between species. We have previously shown that both human and rat hepatocytes express an inducible NO synthase in response to cytokines and lipopolysaccharide. In this study, we compare the expression and regulation of cytokine-induced NO synthase in hepatocytes isolated from three species, human, rat, and mouse. On stimulation with tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interferon gamma (IFN gamma), and lipopolysaccharide (LPS), it was found that hepatocytes from all three species produce high levels of NO with levels of production exhibiting the following hierarchy: rat hepatocytes > mouse hepatocytes > human hepatocytes. Whereas rat and mouse hepatocytes express inducible NO synthase messenger RNA (mRNA) in response to TNF alpha, IL-1 beta, or IFN gamma as a single stimulus, human hepatocytes respond to LPS alone. Inhibition of NO generation through transforming growth factor (TGF-beta 1) was seen in mouse (77% +/- 5.9) and rat hepatocytes (17% +/- 2.6) whereas only about 10% was seen in human hepatocytes. Epidermal growth factor (EGF) was shown to inhibit NO synthesis in human and mouse hepatocytes but not rat. A marked NO-dependent inhibition of total protein synthesis was seen in rat and human hepatocytes, whereas mouse hepatocytes showed almost no inhibition in protein synthesis when stimulated. NO-dependent cyclic guanosine monophosphate (cGMP) release was found in all three species.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Further characterization and comparison of inducible nitric oxide synthase in mouse, rat, and human hepatocytes. 753 95

Products released through the L-arginine/nitric oxide biosynthetic pathway regulate soluble guanyl cyclase activity, which in turn modulates polymorphonuclear leukocyte chemotaxis. We hypothesized that inhibitors of nitric oxide synthase attenuate polymorphonuclear leukocyte chemotaxis in vitro. To test this hypothesis, unstimulated polymorphonuclear leukocytes were pretreated with buffer or the nitric oxide synthase inhibitors NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester, and L-canavanine before being exposed to three structurally unrelated chemoattractants, N-formyl-methionyl-leucyl-phenylalanine, C5a des arginine, and leukotriene B4. Polymorphonuclear leukocyte chemotaxis was quantified with a modified blind-well chamber technique. We found that L-NMMA and L-canavanine but not NG-nitro-L-arginine significantly attenuated polymorphonuclear leukocyte chemotaxis (p < 0.05). L-Arginine but not D-arginine, the nitric oxide donor sodium nitroprusside, and 8-bromo-cyclic guanosine monophosphate restored polymorphonuclear leukocyte chemotaxis attenuated by L-NMMA. Chemotaxis of polymorphonuclear leukocytes primed with lipopolysaccharide (Escherichia coli 0127:B8) or phorbol-13-butyrate was also significantly attenuated by pretreatment with L-NMMA and L-canavanine. Consistent with these observations, intracellular concentrations of cyclic guanosine monophosphate in polymorphonuclear leukocytes was decreased by L-NMMA during exposure to N-formyl-methionyl-leucyl-phenylalanine. These data indicate that nitric oxide synthase inhibitors attenuate chemotaxis of unstimulated and primed polymorphonuclear leukocytes in vitro. We suggest that the L-arginine/nitric oxide biosynthetic pathway plays an important role in regulating polymorphonuclear leukocyte emigration in vivo.
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PMID:Inhibitors of nitric oxide synthase attenuate human neutrophil chemotaxis in vitro. 769 39

Acute endotoxic shock is accompanied by an increase in the production of nitric oxide (NO) by several different hepatic cell types. Platelet-activating factor (PAF) is a potent proinflammatory mediator with many pathophysiological actions and, in fact, elevated plasma and tissue levels of PAF are observed in animal models of endotoxic shock. The current study demonstrates that PAF induced nitrite formation, the end product of nitric oxide synthesis, by Kupffer cells in a dose- and time-dependent manner. Moreover, PAF was seen to initiate NO synthase gene expression and protein synthesis. PAF augmented lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase messenger RNA (mRNA), protein, nitrite and cyclic guanosine monophosphate (cGMP) levels in Kupffer cells. Treatment of Kupffer cells with actinomycin D or cycloheximide inhibited PAF- and LPS-stimulated nitrite and nitric oxide synthase protein formation confirming that de novo synthesis of the enzyme occurred. In Kupffer cells, the presence of an arginine analog, NG-methyl-L-arginine, attenuated nitrite formation induced by PAF and LPS alone or in combination. L-arginine is the principal substrate for nitric oxide synthase. PAF and LPS individually and in combination induced a time-dependent uptake of L-[3H]-arginine into the Kupffer cell, and this response was sensitive to cycloheximide. The current study indicates that exogenous PAF contributes to the induction of nitric oxide synthase by LPS in cultured rat Kupffer cells.
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PMID:Platelet-activating factor augments lipopolysaccharide-induced nitric oxide formation by rat Kupffer cells. 867 86

Interferons (IFN) and lipopolysaccharide (LPS) cause multiple changes in isoprenoid-modified proteins in murine macrophages, the most dramatic being the expression of a prenyl protein of 65 kDa. The guanylate binding proteins (GBPs) are IFN-inducible GTP-binding proteins of approximately 65 kDa that possess a CaaX motif at their C-terminus, indicating that they might be substrates for prenyltransferases. The human GBP1 protein, when expressed in transfected COS-1 cells, incorporates radioactivity from the isoprenoid precursor [3H]mevalonate. In addition, huGBPs expressed from the endogenous genes in IFN-gamma-treated human fibroblasts or monocytic cells were also found to be isoprenoid modified. IFN-gamma-induced huGBPs in HL-60 cells were not labeled by the specific C20 isoprenoid, [3H]geranylgeraniol, but did show decreased isoprenoid incorporation in cells treated with the farnesyl transferase inhibitor BZA-5B, indicating that huGBPs in HL-60 cells are probably modified by a C15 farnesyl rather than the more common C20 lipid. Differentiated HL-60 cells treated with IFN-gamma/LPS showed no change in the profile of constitutive isoprenylated proteins and the IFN-gamma/LPS-induced huGBPs remained prenylated. Despite being prenylated, huGBP1 in COS cells and endogenous huGBPs in HL-60 cells were primarily (approximately 85%) cytosolic. Human GBPs are thus among the select group of prenyl proteins whose synthesis is tightly regulated by a cytokine. HuGBP1 is an abundant protein whose prenylation may be vulnerable to farnesyl transferase inhibitors that are designed to prevent farnesylation of Ras proteins.
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PMID:Prenylation of an interferon-gamma-induced GTP-binding protein: the human guanylate binding protein, huGBP1. 883 Aug


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