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)

1. The inhibitory activity of astrocytoma cells (0.25-3 x 10(5)) treated with indomethacin (10 microM) on platelet aggregation was enhanced by incubating the cells with E. coli lipopolysaccharide (LPS, 0.5 micrograms ml-1) for 18 h. This effect was attenuated when cycloheximide (10 micrograms ml-1) was incubated together with LPS. The inhibition of platelet aggregation by cells treated with LPS was potentiated by superoxide dismutase (60 u ml-1) and ablated by oxyhaemoglobin (oxyHb, 10 microM) or NG-monomethyl-L-arginine (L-NMMA, 30-300 microM). The effects of L-NMMA were reversed by co-incubation with L-arginine (L-Arg, 100 microM) but not D-arginine (D-Arg, 100 microM). LPS also increased the levels of nitrite in the culture media and this increase was ablated by co-incubation with L-NMMA (300 microM) or cycloheximide (10 micrograms ml-1). 2. Astrocytoma cells (0.5 x 10(5)) treated with indomethacin (10 microM) enhanced the platelet inhibitory activity of glyceryl trinitrate (GTN, 11-352 microM) but not that of sodium nitroprusside (4 microM). Furthermore, when incubated with GTN (200 microM) a 4 fold increase in the levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP) was observed. These effects were abrogated by co-incubation with oxyHb (10 microM) but not with L-NMMA (300 microM). Treatment of the cells with LPS (0.5 micrograms ml-1) for 18 h did not enhance their capacity to form NO from GTN. 3. Thus, in cultured astrocytoma cells, LPS enhances the formation of nitric oxide from endogenous L-arginine.In addition, these cells can metabolize GTN to nitric oxide but this process is not enhanced by LPS stimulation.
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PMID:Cultured astrocytoma cells generate a nitric oxide-like factor from endogenous L-arginine and glyceryl trinitrate: effect of E. coli lipopolysaccharide. 132 94

Following treatment with nitrosoguanidine, mutant derivatives of Rhizobium leguminosarum strain 3841 were isolated which failed to react with AFRC MAC 203. This monoclonal antibody normally recognizes a strain-specific lipopolysaccharide epitope which is developmentally regulated during legume nodule differentiation. Structural modification of lipopolysaccharide (LPS) was analysed by examining reactivity with a range of monoclonal antibodies with different epitope specificities, and also by analysis of LPS mobility changes after electrophoresis on polyacrylamide gels. One class of these LPS-defective mutants induced normal nitrogen-fixing (Fix+) nodules on peas (Pisum sativum), while another two classes of Fix- mutants were also identified, suggesting that a component of the LPS antigen that is part of the MAC 203 epitope is essential for normal nodule development leading to symbiotic nitrogen fixation. When grown under low-oxygen or low-pH culture conditions, one class of Fix- mutants completely lacked LPS-1 (the species that carries O antigen) and a second class showed a modified and truncated form of LPS-1. Mutants with defective LPS structure were also obtained after Tn5 mutagenesis of R. leguminosarum 3841 and all nine Fix- mutants were also found to lack the MAC 203 epitope. Three of these transposon-induced mutants synthesized a truncated form of LPS-1 that was structurally similar to that of the class of the NTG-induced mutants described above. These transposon-induced mutations, and the nitrosoguanidine-induced Fix- mutations, were closely linked and could be suppressed by the same cloned fragment of chromosomal DNA. The data presented here suggest that a precondition for normal nodule development of R. leguminosarum 3841 within pea nodules is the ability to synthesize relatively long-chain LPS-1 macromolecules under the physiological conditions encountered within the nodule. All mutants that lacked the ability to elongate LPS-1 macromolecules also failed to express the MAC 203 epitope.
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PMID:Molecular dissection of structure and function in the lipopolysaccharide of Rhizobium leguminosarum strain 3841 using monoclonal antibodies and genetic analysis. 138 72

To determine the role that vasoactive neuropeptides, calcitonin gene-related peptide, and substance P play in tissue-blood flow regulation during early septic shock, we examined the responsiveness of arteries removed from pigs 3 h after administration of Escherichia coli lipopolysaccharide or saline vehicle. The carotid, cranial mesenteric, and left anterior descending coronary arteries were excised, and rings were cut from each vessel. Constrictor responses were obtained to cumulative doses of norepinephrine or potassium chloride. Rings were reconstricted and challenged with acetylcholine, substance P, calcitonin gene-related peptide, and nitroglycerin. Lipopolysaccharide significantly increased the cranial mesenteric artery's response to high concentrations of norepinephrine and the response to nitroglycerin in all vessels. This enhancement of responses to nitroglycerin suggests augmented smooth-muscle responsiveness to an exogenous source of nitric oxide, possibly associated with early depression of basal endothelial function. Depression of agonist-induced nitric oxide release may mask such enhancement with endothelial-dependent dilators and may enhance the response to adrenergic constrictors in some vascular beds.
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PMID:Early endotoxic shock results in enhanced vasodilator responses to nitroglycerin but unaltered responses to neuropeptides calcitonin gene-related peptide and substance P. 753 18

Nitric oxide (NO) synthesized from L-arginine is an endogenous vasodilator and inhibitor of platelet adhesion and aggregation. Gram-negative lipopolysaccharide (LPS) can induce NO synthesis, which may mediate the pathophysiologic effects of endotoxemia. In addition, our previous studies suggested that LPS-induced NO may protect against thrombosis in rats. In the present study, male Sprague-Dawley rats given LPS (0.1 mg/kg) i.p. increased their urinary excretion of NO2 + NO3 (stable end-products of NO) by 4.3-fold. Rats given 10 micrograms/kg/hr i.v. of nitroglycerin (GTN), an exogenous NO donor, showed a similar increase. L-NAME, an inhibitor of NO synthesis, abrogated the increase in urinary NO2 + NO3 in LPS-treated rats but not in rats given GTN. Glomerular thrombosis developed in rats given LPS + L-NAME (thrombosis score = 3.02 +/- 0.4), while those given LPS + L-NAME + GTN were largely protected (thrombosis score = 1.37 +/- 0.5, P < 0.05). Atrial natriuretic peptide (ANP), an NO-independent vasodilator, neither increased urinary NO2 + NO3 nor prevented glomerular thrombosis (thrombosis score = 2.68 +/- 0.5, NS). Hydralazine, another vasodilator without effects on NO or platelets, also failed to prevent glomerular thrombosis in rats given LPS + L-NAME. We conclude that in endotoxemia, the antithrombogenic properties of endogenously synthesized NO are important in preventing alomerular thrombosis. The exogenously NO donor, GTN, can substitute for the antithrombogenic effect of endogenous NO. Clinically, administration of NO synthesis inhibitors to treat endotoxic shock may need to be combined with concomitant administration of exogenous NO donors to prevent microvascular thrombosis.
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PMID:Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats. 799 92

Role of endothelium-derived relaxing factor on vascular reactivity in endotoxin-induced shock. Chinese J. Physiol. The present study showed that E. coli lipopolysaccharide (LPS; 5 mg/kg, i.v.) produced a maximal and significant reduction in mean arterial blood pressure in the anesthetized rat. Pretreatment with N omega-nitro-L-arginine (50 mg/kg, i.v.) produced an increase in mean arterial blood pressure and completely abolished the LPS-induced hypotension. In vitro, it was designed to analyse the mechanisms underlying the LPS-induced hypotension by using various contractile and relaxant agents. Phenylephrine and high-K(+)-induced contraction was less in mesenteric arterial rings from LPS-treated rats than in rings from control rats. The removal of endothelium significantly enhanced the contraction induced by phenylephrine and high-K+ in LPS-treated rats, whereas in control rats, only the contraction induced by phenylephrine was enhanced. In contrast, the relaxation elicited by acetylcholine, A23187, L-arginine and nitroglycerin was greater in mesenteric arterial rings from LPS-treated rats than those from control rats. However, the greater relaxation induced by acetylcholine in LPS-treated rats was completely abolished by N omega-nitro-L-arginine or methylene blue. Additionally, the acetylcholine-induced relaxation was absent by removal of the endothelium. These results suggest that LPS treatment induces the production of nitric oxide from vascular endothelial cells and/or smooth muscle cells then impair the contractile response to vasoconstrictors and enhance the relaxation to vasodilators in small mesenteric arteries.
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PMID:Role of endothelium-derived relaxing factor on vascular reactivity in endotoxin-induced shock. 802 Mar 37

The purpose of this study was to determine whether short-term exposure of resistance arterioles to lipopolysaccharide in situ is associated with changes in vasomotor tone. Using intravital microscopy, we found that suffusion of Escherichia coli lipopolysaccharide (3 micrograms/ml) over hamster cheek pouch arterioles for 1 h was associated with a significant immediate biphasic response: vasoconstriction followed by vasodilation (p < 0.05). The former was attenuated by indomethacin, and the latter by SK&F 108566, a selective, non-peptide angiotension II receptor antagonist (p < 0.05). The nitric oxide synthase inhibitor, NG-L-nitro arginine, had no significant effects on lipopolysaccharide-induced responses. Allopurinol, a scavenger of reactive oxygen species, significantly attenuated lipopolysaccharide-induced vasodilation. Acetylcholine- and nitroglycerin-induced vasodilation were significantly potentiated after lipopolysaccharide. These responses were recorded in the absence of any significant changes in systemic arterial blood pressure. Collectively, these data suggest that short-term exposure of the peripheral microcirculation to lipopolysaccharide in situ is associated with an ischemia-reperfusion-like injury. These changes may contribute to end organ failure observed several hours after exposure to lipopolysaccharide.
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PMID:Short-term exposure to lipopolysaccharide is associated with microvascular contractile dysfunction in vivo. 861 41

Nitroglycerin (GTN) produces a dilation of vascular smooth muscle by releasing NO through a putative GTN-converting step. However, the response to GTN is markedly attenuated after prolonged or repeated exposure, resulting in tolerance. We investigated the mechanisms of GTN tolerance, employing exogenous and endogenous NO in rat aorta. In endothelium-denuded rat aortic strips, the GTN-induced relaxation response was attenuated by preceding exposure to either GTN or sodium nitroprusside (SNP). In contrast, the SNP-induced relaxation response was not affected by this protocol of GTN or SNP preexposure. Preincubation of aortic strips with lipopolysaccharide (LPS) +/- L-arginine for 12 h also caused attenuation of GTN-induced responses such as relaxation, cGMP production and nitrite/nitrate formation. The attenuating effect of LPS abolished in aortic strips co-incubated with LPS and cycloheximide or N(G)-nitro-L-arginine. These results suggest that GTN tolerance is predominantly associated with the reduction of NO release from GTN, which is caused through inhibition of a GTN-converting step due to preceding exposure to NO itself.
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PMID:Possible involvement of nitroglycerin converting step in nitroglycerin tolerance. 1037 9

The purpose of this study was to determine whether short-term exposure to clinically relevant concentrations of Pseudomonas aeruginosa lipopolysaccharide (LPS) impairs vasoreactivity of resistance arterioles in the intact spinotrapezius muscle microcirculation and, if so, to determine the mechanisms mediating this response. Using intravital microscopy, we found that 60-min suffusion of P. aeruginosa LPS (0.03-3.0 microg/ml) on the in situ hamster spinotrapezius muscle elicited an immediate, profound, and prolonged concentration-dependent vasodilation (P < 0.05). This response was reversible once suffusion of P. aeruginosa LPS was stopped. Pretreatment with N(G)-nitro-L-arginine methyl ester (10.0 microM), a nonselective nitric oxide (NO) synthase inhibitor, but not N(G)-nitro-D-arginine methyl ester, abrogated P. aeruginosa LPS-induced vasodilation and elicited a small, albeit significant, vasoconstriction. Indomethacin had no significant effects on P. aeruginosa LPS-induced responses. P. aeruginosa LPS had no significant effects on acetylcholine- and nitroglycerin-induced vasodilation in the spinotrapezius muscle. Collectively, these data indicate that short-term exposure to clinically relevant concentrations of P. aeruginosa LPS evokes an immediate, potent, prolonged, and reversible NO-dependent, prostaglandin-independent vasodilation in skeletal muscles in vivo. We suggest this response could play an important role in the pathophysiology of the profound vasomotor dysfunction observed in the peripheral circulation of patients with P. aeruginosa sepsis syndrome.
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PMID:Effects of Pseudomonas aeruginosa endotoxin on vasodilation in the intact spinotrapezius muscle. 1140 51

Glyceryl nonivamide (GLNVA), a vanilloid receptor (VR) agonist, has been reported to have calcitonin gene-related peptide-associated vasodilatation and to prevent subarachnoid hemorrhage-induced cerebral vasospasm. In this study, we investigated the neuroprotective effects of GLNVA on activated microglia-like cell mediated- and proparkinsonian neurotoxin 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. In coculture conditions, we used lipopolysaccharide (LPS)-stimulated BV-2 cells as a model of activated microglia. LPS-induced neuronal death was significantly inhibited by diphenylene iodonium (DPI), an inhibitor of NADPH oxidase. However, capsazepine, the selective VR1 antagonist, did not block the neuroprotective effects of GLNVA. GLNVA reduced LPS-activated microglia-mediated neuronal death, but it lacked protection in DPI-pretreated cultures. GLNVA also decreased LPS activated microglia induced overexpression of neuronal nitric-oxide synthase (nNOS) and glycoprotein 91 phagocyte oxidase (gp91(phox)) on SH-SY5Y cells. Pretreatment of BV-2 cells with GLNVA diminished LPS-induced nitric oxide production, overexpression of inducible nitric-oxide synthase (iNOS), and gp91(phox) and intracellular reactive oxygen species (iROS). GLNVA also reduced cyclooxygenase (COX)-2 expression, inhibitor of nuclear factor (NF)-kappaB (IkappaB)alpha/IkappaBbeta degradation, NF-kappaB activation, and the overproduction of tumor necrosis factor-alpha, interleukin (IL)-1beta, and prostaglandin E2 in BV-2 cells. However, GLNVA augmented anti-inflammatory cytokine IL-10 production on LPS-stimulated BV-2 cells. Furthermore, in 6-OHDA-treated SH-SY5Y cells, GLNVA rescued the changes in condensed nuclear and apoptotic bodies, prevented the decrease in mitochondrial membrane potential, and reduced cells death. GLNVA also suppressed accumulation of iROS and up-regulated heme oxygenase-1 expression. 6-OHDA-induced overexpression of nNOS, iNOS, COX-2, and gp91(phox) was also reduced by GLNVA. In summary, the neuroprotective effects of GLNVA are mediated, at least in part, by decreasing the inflammation- and oxidative stress-associated factors induced by microglia and 6-OHDA.
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PMID:Neuroprotective effects of glyceryl nonivamide against microglia-like cells and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells. 1785 75

Mammalian myeloid and epithelial cells express various peptide antibiotics (such as defensin and cathelicidin) that contribute to the innate host defense against invading microorganisms. Among these, guinea pig cathelicidin CAP11 (G1-I43) possesses potent antibacterial activities against Gram-positive and -negative bacteria, and also lipopolysaccharide-neutralizing activity. We previously revealed that the active region with antibacterial activity is localized at G1 to R18 of CAP11. In this study, to develop peptide derivatives with enhanced antimicrobial actions, we utilized the amphipathic 18-mer peptide (G1-R18) as a template. Anti-microbial activities of the peptides were assessed by alamarBlue assay (Escherichia coli, Staphylococcus aureus and Candida albicans) and colony formation assay (Porphyromonas gingivalis). Furthermore, the membrane-permeabilization activities were determined by using E. coli ML-35p as a target. By substituting K5, T9, R10, R12, and G17 with five L residues, the hydrophobicity of the peptide (1-18m1) was increased, and by substituting G1, and Q14 with K and R residues, respectively, the hydrophilicity (positive charge) of the peptide (1-18m2) was enhanced. Among the peptides, 1-18m2 exhibits the most potent antimicrobial and membrane-permeabilizing activities against the microorganisms examined. Thus, the antimicrobial activities of the amphipathic CAP11-derived 18-mer peptide can be augmented by modifying its hydrophobicity and hydrophilicity (positive charge), and 1-18m2 is the most potent among the peptide derivatives with therapeutic potential for Gram-positive and -negative bacterial, and fungal infections.
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PMID:Augmentation of the antimicrobial activities of guinea pig cathelicidin CAP11-derived peptides by amino acid substitutions. 1928 26


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