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)

Membrane vesicles were prepared from Azotobacter vinelandii spheroplasts by lysis in either potassium phosphate (pH 7.0) or Tris1-acetate (pH 7.8) buffers. These 2 types of preparations differ considerably in their properties: 1) Examination by scanning electron microscopy reveals that the Pi vesicles consist primarily of closed structures 0.6-0.8 micrometer in diameter with a rough or particulate surface similar to that of spheroplasts. The Tris vesicles are significantly smaller, 0.1-0.3 micrometer in diameter, and have a much smoother surface structure. 2) Antisera from rabbits immunized with A. vinelandii lipopolysaccharide antigen will agglutinate Pi vesicles but not Tris vesicles. 3) Tris vesicles have a fourfold higher specific activity of latent H+-ATPase than Pi vesicles. After exposure to Triton X-100 similar ATPase activities are observed for both types of vesicles. 4) Pi vesicles transport calcium in the presence of ATP or lactate at less than 30% of the rats observed for Tris vesicles. 5) Tris vesicles have less than 22% of the transport capacity of Pi vesicles for accumulation of labeled sucrose and less than 3% of the capacity for valinomycin-induced uptake of rubidium observed during respiration. 6) Quinacrine fluorescence intensity is reduced by 30% during lactate oxidation and 20% during ATP hydrolysis by Tris vesicles. Under similar conditions, fluorescence in Pi vesicles is quenched by only 7% and less than 2%, respectively. These findings suggest that Pi vesicles have the normal orientation of the intact cell whereas Tris vesicles have an inverted topology.
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PMID:Isolation of membrane vesicles with inverted topology by osmotic lysis of Azotobacter vinelandii spheroplasts. 14 14

Bactericidal activity has been assessed for a number of glycolmonophenyl ethers towards Escherichia coli NCTC 5933, and the action of one analogue, 2-phenoxyethanol, has been studied in greater detail. For this compound the onset of bactericidal activity towards Escherichia coli occurred at concentrations which also induced considerable increases in drug uptake, marked leakage of cytoplasmic constituents, the cellular penetration of N-tolyl-alpha-napthylamine-8-sulphonic acid, and morphological changes consistent with gross membrane damage. However, temperature coefficients of rates of cellular leakage of low molecular weight cytoplasmic constituents, and rates of kill, were markedly different and suggested that the two phenomena were not integrally related, but that each was a consequence of some other action of the drug. Drug levels considerably below those possessing lethal activity, however, promoted the ready efflux of potassium ions from cells and caused disorganisation of the outer lipopolysaccharide-rich regions of the cell envelope.
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PMID:The lethal action of 2-phenoxyethanol and its analogues upon Escherichia coli NCTC 5933. 36 38

Exponentially grown cells of Escherichia coli K-12 heated at 48 degrees C in potassium phosphate buffer at pH 7.0 were structrually injured before death. During heating for 60 min about 20% of the cellular lipopolysaccharide (LPS) was released from the outer membrane into the heating medium. Removal of 30% of the cellular LPS, by washing the cells in buffer containing ethylenediaminetetraacetic acid (EDTA), caused no significant increase in the rate of death and structural injury produced by heating. The addition of EDTA to the heating medium produced only a slight increase in the rate of thermal death but a large increase in the rate of structural injury. By a combination of heating at 48 degrees C and washing with EDTA, a maximum of 50% of the LPS was released from cells. These results taken together suggest that structural injury and loss of LPS are not the direct causes of death. The addition of 5 m M Mg2+ to the heating medium protected the cells from death and structural injury caused by heating at 48 degrees C.
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PMID:Outer-membrane damage in sublethally heated Escherichia coli K-12. 40 6

Several investigators have reported lipid A as the biologically active unit in the lipopolysaccharide (LPS) molecule. To determine if lipid A was responsible for the reported increases in pyruvate kinase, mice were injected with endotoxin from Salmonella typhimurium SR-11, the Re mutant of Salmonella minnesota R 595, and lipid A-bovine serum albumin conjugate. The livers were homogenized and the activity of pyruvate kinase was measured. Similar increases in enzyme were obtained with all three preparations. These data imply that the lipid portion of the LPS molecule was responsible for alterations in host enzyme activity. To further determine if the lipid portion was the active unit, a lipid-degraded endotoxin (endotoxoid) prepared by potassium methylate treatment was inoculated into mice. An initial increase in liver pyruvate kinase activity was observed with all preparations. The marked increase observed at 16 h with the native product and lipid A conjugate was not obtained with the endotoxoid. These experiments extend and confirm previous observations that lipid A is responsible for the effects associated with LPS. Animals tolerant to endotoxin from S. typhimurium SR-11 were challenged with endotoxin from the Re mutant. A significant increase in pyruvate kinase activity was not obtained, suggesting that anti-O antibodies are not important in the development of tolerance.
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PMID:Effect of lipopolysaccharide and lipid A on mouse liver pyruvate kinase activity. 110 89

Different antigens of Pasteurella multocida Carter's type 6:B including whole bacterium, antigen heated at 56 degrees C, antigen heated at 100 degrees C, sonicated antigen, capsular antigen, potassium thiocyanate extract, lipopolysaccharide and sodium salicylate extract were evaluated to assess protection in buffalo calves against haemorrhagic septicaemia. Sera from calves with known protection status in experimental challenge were titrated by enzyme-linked immunosorbent assay (ELISA) against all antigens. Capsular antigen extracted with 2.5% sodium chloride was superior to other antigens for assessing protection status of buffalo calves against P. multocida by ELISA. This capsular antigen was able to differentiate clearly between well-protected, protected and unprotected animals.
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PMID:Serological evaluation of Pasteurella multocida antigens associated with protection in buffalo calves. 147 36

The potassium channel activator nicorandil, under evaluation for antianginal management, has been shown to decrease neutrophil respiratory burst. Since our laboratory has demonstrated that reactive oxygen species (ROS) increase tumor necrosis factor (TNF) production, we hypothesized that nicorandil might decrease TNF production from a lipopolysaccharide (LPS) challenge via reduction of respiratory burst. Macrophage viability and TNF production were determined after an 18-hr exposure to 5.0 micrograms/ml LPS and varying concentrations of nicorandil. Nicorandil was not toxic to macrophages below 12 mM (94 +/- 3% viability versus control) and decreased ROS and TNF production. Intracellular superoxide production decreased from 164 +/- 24 OD550 to 99 +/- 6 OD550 with 10 mM nicorandil and extracellular superoxide decreased from 3108 +/- 111 to 1760 +/- 210 nM. Hydrogen peroxide production was also decreased by 10 mM nicorandil. TNF production in response to 5 micrograms/ml LPS decreased from 6.8 +/- 0.6 to 2.7 +/- 0.4 ng/ml with 10 mM nicorandil. Northern and slot blot analyses demonstrate that nicorandil acts at a post-transcriptional site. These data imply that nicorandil decreases macrophage TNF production from an LPS challenge, possibly through a reduction in respiratory burst. Such compounds may prove useful in the treatment of conditions thought to be associated with free radical-lymphokine interactions such as ischemia-reperfusion injury, oxygen toxicity, adult respiratory distress syndrome, and septic shock.
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PMID:Alterations in macrophage free radical and tumor necrosis factor production by a potassium channel activator. 153 87

The mechanism by which 4-aminopyridine (4-AP) blocks the delayed rectifier type potassium (K+) channels present on lipopolysaccharide-activated murine B lymphocytes was investigated using whole-cell and single channel patch-clamp recordings. 4-AP (1 microM-5 mM) was superfused for 3-4 min before applying depolarizing pulses to activate the channel. During the first pulse after application of 4-AP above 50 microM, the current inactivated faster, as compared with the control, but its peak was only reduced at high concentrations of 4-AP (Kd = 3.1 mM). During subsequent pulses, the peak current was decreased (Kd = 120 microM), but the inactivation rate was slower than in the control, a feature that could be explained by a slow unblocking process. After washing out the drug, the current elicited by the first voltage step was still markedly reduced, as compared with the control one, and displayed very slow activation and inactivation kinetics; this suggests that the K+ channels move from a blocked to an unblocked state slowly during the depolarizing pulse. These results show that 4-AP blocks K+ channels in their open state and that the drug remains trapped in the channel once it is closed. On the basis of the analysis of the current kinetics during unblocking, we suggest that two pathways lead from the blocked to the unblocked states. Computer simulations were used to investigate the mechanism of action of 4-AP. The simulations suggest that 4-AP must bind to both an open and a nonconducting state of the channel. It is postulated that the latter is either the inactivated channel or a site on closed channels only accessible to the drug once the cell has been depolarized. Using inside- and outside-out patch recordings, we found that 4-AP only blocks channels from the intracellular side of the membrane and acts by reducing the mean burst time. 4-AP is a weak base (pK = 9), and thus exists in ionized or nonionized form. Since the Kd of channel block depends on both internal and external pH, we suggest that 4-AP crosses the membrane in its nonionized form and acts from inside the cell in its ionized form.
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PMID:Mechanism of 4-aminopyridine action on voltage-gated potassium channels in lymphocytes. 161 84

Bleomycin (BLM) has been successfully used to treat a number of human neoplasms. The main toxicity associated with BLM therapy is an acute pulmonary inflammation that can culminate in diffuse chronic fibrosis. The effect of BLM-induced pulmonary inflammation on the cytostatic activity of alveolar macrophages (AM) was investigated using AM obtained from rats that had been previously treated with BLM. Bronchoalveolar lavage fluid was collected at selected time intervals following a single fibrogenic dose of intratracheally administered BLM (3.6 mg/kg). AM obtained 12 to 72 h following intratracheal BLM (BLM-AM) caused cytostasis of murine leukemia L1210 cells in co-culture, whereas AM obtained from saline-treated controls were not cytostatic. These results indicate that the growth-inhibitory activity of the AM was related to the pulmonary inflammation. Cytostatic activity in control AM could be induced by in vitro exposure to lipopolysaccharide (5 micrograms). When RBC were added to the AM-L1210 co-culture, the cytostatic activity of the BLM-AM was abrogated. The fact that chemical treatment of the RBC with sodium nitrite and potassium cyanide or N-ethylmaleimide did not alter the ability of the RBC to abrogate AM cytostatic activity suggests that the RBC is not acting as a scavenger of oxygen radicals. In contrast, the addition of FeSO4 to the AM-L1210 co-culture mimicked the effect of RBC addition. Aconitase, an iron-sulfur-containing enzyme necessary for mitochondrial respiration, is decreased in L1210 cells that have been co-cultured with BLM-AM but not when the co-cultures also contain RBC. These results suggest that (a) pulmonary inflammation induces cytostatic activity in AM, (b) the alteration of iron homeostasis plays an important role in this cytostatic process, and (c) RBC can prevent this cytostatic activity.
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PMID:Effect of erythrocytes on alveolar macrophage cytostatic activity induced by bleomycin lung damage in rats. 169 May 96

Potassium peroxydiphosphate (KPDP) is a slowly hydrolyzed pyrophosphate analog that can release hydrogen peroxide during hydrolysis. We tested its effects on the resorption of cultured fetal rat long bones as measured by the release of previously incorporated 45Ca, both by direct addition of KPDP to the medium and after preincubation of KPDP with large-molecular-weight resorbing factors followed by dialysis to reduce the KPDP concentration. With direct addition, KPDP at a concentration of 1 mM could inhibit the resortive response to bacterial lipopolysaccharide (LPS), parathyroid hormone (PTH), prostaglandin E2 (PGE2), and mouse recombinant interleukin-1 (mrIL-1). The response to LPS was partially inhibited at 0.3 mM KPDP. Control resorption in the absence of stimulators was also inhibited. Potassium pyrophosphate at 1 mM was less effective as an inhibitor of bone resorption. The inhibitory effects of KPDP did not appear to be due entirely to nonspecific toxicity since partial recovery occurred after it was removed. There was no significant decrease in [3H]thymidine or [3H]proline incorporation into bones incubated with KPDP at 1 mM for 5 days, but [3H]proline incorporation was decreased at 24 h, suggesting that KPDP may have a general inhibitory effect on bone cells. When media with and without stimulators of resorption were incubated overnight at 4 degrees C with KPDP at 5.8 mM and then dialyzed to bring the concentration to below 0.3 mM, the bone-resorbing activity of PTH, LPS, and mrIL-1 was completely lost. This may have been due to the slow release of hydrogen peroxide; however, preincubation with equimolar concentrations of H2O3 caused only partial inactivation of PTH and LPS. LPS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of potassium peroxydiphosphate on bone resorption. 179 51

Decreased responsiveness of the vasculature to vasoconstrictors has been implicated in the pathogenesis of endotoxic shock, yet the mechanism of diminished responsiveness has not been determined. In these studies, exposure of rat aortic rings to purified Escherichia coli lipopolysaccharide (endotoxin) in vitro inhibited subsequent contractions caused by vasoconstrictors. Contractions caused by the alpha-adrenoceptor agonist phenylephrine, as well as those induced by potassium depolarization, were depressed by endotoxin. The effect of endotoxin on vascular contractions was delayed. Phenylephrine-induced contractions were not decreased during a 1-h exposure to endotoxin (10 micrograms/ml), but they were markedly decreased when tested several hours after the exposure period. A large part of the inhibition caused by a 1-h exposure to endotoxin was endothelium dependent. In contrast, endotoxin inhibited contractions equally in rings with or without endothelium exposed to endotoxin for a longer period (3 h). The inhibitory effect of endotoxin was not affected by indomethacin, but it was eliminated in aortic rings treated with the protein synthesis inhibitor cycloheximide. These studies indicate that endotoxin potently inhibits vascular contraction in vitro. The effect of endotoxin is apparently independent of prostanoids but may involve protein synthesis and effects on both vascular smooth muscle and endothelial cells.
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PMID:Endotoxin inhibits contraction of vascular smooth muscle in vitro. 218 81


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