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)

A rat model was used to study the effects of endotoxemic shock in vivo on diaphragmatic tension generation and diaphragmatic metabolism in vitro. Animals were injected with E. coli lipopolysaccharide (30 mg/kg) and killed at fixed times after injection. The hemidiaphragms were isolated in an organ bath, and tension generation was measured during electrical stimulation of the phrenic nerve or diaphragmatic muscle. Diaphragmatic oxygen consumption was measured in vitro during rest and during in vivo stimulation. Adenosine triphosphate and glycogen concentrations were measured in vivo before the animals were killed and in vitro. Tension generation was reduced in a time-dependent fashion after endotoxin at all stimulation frequencies. Both contractile fatigue and transmission fatigue were present. Glycogen stores were reduced but not depleted. ATP concentration was reduced in vivo but recovered in vitro. Diaphragmatic oxygen consumption was reduced in vitro at rest and during stimulation. The results suggest that endotoxemic shock results in diaphragmatic fatigue in a time-dependent fashion, that impaired neural or neuromuscular transmission is present in vitro, and that impaired oxygen consumption in the shocked diaphragm is associated with reduced high-energy-phosphate stores.
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PMID:Diaphragmatic fatigue after endotoxemic shock in rats: in vitro function and metabolism. 221 69

Lipid A, the toxic principle of endotoxic lipopolysaccharide, and its precursor, Lipid X, interact with human platelets and modulate protein kinase C therein (Grabarek, J., Timmons, S., and Hawiger, J. (1988) J. Clin. Invest. 82, 964-971). We have now purified protein kinase C from human platelets and studied its interaction with endotoxic Lipids A and X. Protein kinase C-dependent phosphorylation of histone III-S was increased 15 times in the presence of Lipid A and 300 microM Ca2+. The Ca2+ requirement for such activation was lower when 4 beta-phorbol 12-myristate 13-acetate (PMA) or 1,2-diolein were added. Lipid A also induced autophosphorylation of protein kinase C, and its activation was enhanced by phosphatidylserine without reducing the Ca2+ requirement. Kinetic analysis of protein kinase C activation induced by Lipid A, in regard to ATP as a substrate, demonstrated that Lipid A increased the rate of the reaction (Vmax) without modifying the affinity of the enzyme (Km) for the substrate. Lipid X inhibited the activation of the enzyme induced by Lipid A. Lipid X also inhibited protein kinase C activation by phosphatidylserine, 1,2-diolein, and PMA. However, 10 times more of Lipid X was required for 50% inhibition (IC50) when PMA was used as an activator of protein kinase C in the presence of phosphatidylserine than when Lipid A and 1,2-diolein were used. These results support the hypothesis that endotoxic Lipid A and Lipid X exert their biological effect in platelets through direct interactions with protein kinase C.
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PMID:Interaction of endotoxic lipid A and lipid X with purified human platelet protein kinase C. 229 55

Interferon or 2'-5' oligoadenylates (2'-5' An) activated the microbicidal activity of primary cultures of rat glia cells and of the mouse macrophage transformed cell line J774 against infection by Trypanosoma cruzi. Pretreatment with gamma-interferon (gamma-IFN) or 2'-5' A3 of rat glia cells or direct addition of these compounds during the incubation with the parasite enhanced the uptake of metacyclic trypanosomes by the cells. Furthermore, glia cells treated with gamma-IFN or 2'-5' A3 were able to restrict the growth and to eventually destroy intracellular amastigotes. Bacterial lipopolysaccharide (LPS) synergized with gamma-IFN as well as with 2'-5' A3 and 2'-5' A4, but not with dephosphorylated 'core' molecules or ATP, to induce a partial trypanocidal activity in J774 cells. In addition, those treatments with gamma-IFN or 2'-5' A3 activated to a similar extent an endoribonuclease, which degraded ribosomal RNA, in rat glia cells, suggesting a role of this enzyme in the mechanism of the trypanocidal activity of gamma-IFN.
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PMID:Stimulation of the trypanocidal and endoribonuclease activities by the interferon induced (2'-5') oligoadenylates. 244 17

In pursuing the mechanism of endotoxin action, we examined the effect of lipopolysaccharide (LPS) and its chemically defined components, lipid A and lipid X on cultured bovine endothelial cells. We report that LPS and lipid A caused detachment and altered morphology of endothelial cells while lipid X did not. Phorbol myristate acetate, a compound known to activate protein kinase C, also caused endothelial cell detachment. Morphologic changes were readily apparent in the endothelial cells after 6 hours of exposure to lipopolysaccharide (1 microgram/ml); at that time many of the cells had contracted and formed bleblike structures on the surface. Large vacuoles, dense bodies, and pyknotic nuclei were found in the detaching cells, indicating necrosis or cell death. Preceding the morphologic changes and actual detachment, endothelial cell DNA and RNA synthesis was impaired by LPS. The changes in DNA and RNA synthesis occurred within 4 hours of exposure to 1 microgram/ml of LPS when the cells were still able to maintain normal levels of ATP. In addition to the inhibition of nucleic acid synthesis, protein synthesis was inhibited after 6 and 8 hours of LPS exposure. DNA, RNA, and protein synthesis returned to control levels after 24 hours of exposure. Investigation on the cultured bovine endothelial cells as a model for LPS action was useful in that these cells are sensitive to relatively low levels of LPS and the endothelium may be an important target in sepsis.
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PMID:Effects of lipopolysaccharide, lipid A, lipid X, and phorbol ester on cultured bovine endothelial cells. 245 32

ATPase activity of elementary bodies (EBs) of Chlamydia trachomatis was investigated by using high-resolution 31P nuclear magnetic resonance spectroscopy. ATPase activity was detected in EBs of C. trachomatis serovars A, B, and L2 after treatment with the reducing agents 2-mercaptoethanol and glutathione. ATPase activity was oligomycin sensitive and magnesium ion dependent. EBs heated at 60 degrees C for 10 min or pretreated with Triton X-100 before exposure to 2-mercaptoethanol did not exhibit ATPase activity. Monoclonal antibody to the major outer membrane protein abrogated ATPase activity of EBs, whereas monoclonal antibody to chlamydial lipopolysaccharide only marginally reduced the level of ATPase activity. These findings suggest that EBs possess intrinsic ATPase activity and that cysteine-rich outer membrane proteins of EBs are important in the regulation of ATPase activity. The major outer membrane protein may be the major route through which ATP accesses ATPase.
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PMID:High-resolution 31P nuclear magnetic resonance study of Chlamydia trachomatis: induction of ATPase activity in elementary bodies. 253 Jan 75

Recent evidence has implicated enkephalins as immunomodulators. Several studies have reported the regulation of tumor growth by methionine enkephalin (ME). However, there has been little effort to relate the immunological significance of enkephalins to the development of anticancer drugs. The present study had three aims: first, to compare the antitumor activity of the synthetic peptide, D-[Ala2]methionine enkephalinamide (MEA), with endogenous enkephalins on PYB6 fibrosarcoma tumor growth; second, to determine whether tumor growth inhibition was mediated by an opiate receptor; and third, to investigate the effects of MEA on selected immune responses. Female B6C3F1 mice were injected i.p. daily for 7 days with 50-4000 micrograms/kg of ME, MEA, leucine enkephalin (LE) or D-[Ala2]leucine enkephalinamide (LEA), beginning 1 day after PYB6 inoculation. ME and MEA, but not LE or LEA, decreased the PYB6 growth rate. The dose of 50 micrograms/kg MEA exerted the maximum inhibition of tumor growth (nearly 72% on day 15 post tumor transplantation). MEA was not directly toxic to PYB6 tumor cells, as evaluated by the measurement of DNA synthesis and cellular ATP levels of PYB6 cells exposed to MEA in vitro. No [3H]-etorphine specific bindings were detected on the cell membrane or sonicates of splenic lymphocytes or PYB6 cells. Therefore, the antitumor activity by MEA is likely mediated by an indirect mechanism. Immunological studies indicated that MEA selectively enhanced the lymphoproliferative response to the T-cell mitogen, concanavalin A, but not to the B-cell mitogen, lipopolysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antitumor activity of enkephalin analogues in inhibiting PYB6 tumor growth in mice and immunological effects of methionine enkephalinamide. 255 21

Exposure of plasma membranes isolated from high density resting murine B cells to recombinant IL-4 in the presence of gamma-[32P]-ATP promoted phosphorylation of a protein of Mr = 42,000. The 42 Kd protein kinase substrate could be detected in membranes prepared from low density B cells following a 24 h culture with lipopolysaccharide, but not in membranes prepared from B cells exposed to LPS for 48 h. Treatment of the cells with LPS resulted in the appearance of a number of new membrane-associated phosphoproteins. Treatment with the cytokine also resulted in the disappearance of a protein kinase substrate of Mr = 30,000 from phosphoprotein profiles of membranes prepared from cells exposed to LPS for 24 h. The 42 Kd structure appears to be a protein kinase substrate rather than possessing intrinsic phosphotransferase activity as judged from experiments employing 8-azido-gamma-[32P]-ATP as a photoaffinity label. No 42 Kd species was detectable using this reagent. Experiments employing identical protocols failed to reveal any enhanced or diminished phosphorylation of membrane-associated proteins in human peripheral blood B cells or in human B lymphoma cell lines.
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PMID:The effect of recombinant interleukin 4 upon protein kinase activities associated with murine and human B lymphocyte plasma membranes. 264 82

Genotoxic activities of a series of commercially purchased 1,N6-ethenoadenosine (epsilon-Ado) and epsilon-deoxyadenosine (epsilon-dAdo) derivatives were assessed using the sister chromatid exchange (SCE) assay in murine spleen lymphocytes in vitro. Of the epsilon-Ado adducts evaluated for SCE induction epsilon-ATP and epsilon-dATP were highly active (5x baseline) SCE inducers over a concentration range of 50-150 microM. Moderate SCE-inducing activities were seen with epsilon-dAdo, epsilon-A, and epsilon-AMP. epsilon-A was of particular interest in that spleen lymphocytes from a single mouse were highly sensitive to SCE (greater than 50 SCE/cell at 75 microM). epsilon-Ado was weakly effective and epsilon-ADP and epsilon-dAMP did not produce significantly elevated SCEs. Cocanavalin A-stimulated T-lymphocytes and lipopolysaccharide-stimulated B-lymphocytes exhibited comparable SCE responses to epsilon-A, epsilon-AMP, and epsilon-dATP. However, B-lymphocytes were considerably less sensitive than T-lymphocytes to epsilon-dAdo and epsilon-ATP. Evaluation of the purities of specific epsilon-Ado derivatives, as performed by high-performance liquid chromatography and thin layer chromatography, failed to detect potential contaminants as cytogenetically active agents. However, a difference (about threefold) in cytogenetic activities of two lot numbers of epsilon-ATP paralleled the difference in UV absorbance of quivalent concentrations (mg/ml), prepared according to the manufacturers stated purity. Any impurities likely to be present were consistent with inactive nonchromophoric compounds such as buffer salts. Because of the direct genotoxic activity of epsilon-A in intact mammalian cells, we suggest that intracellular adenylate pools, including the prominent ubiquitous nucleotide ATP, are non-DNA targets for epsilon-modification by active metabolites and the resulting epsilon-adducts are likely to be active moieties in SCE induction and in neoplastic transformation produced by ethyl carbamate.
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PMID:Sister chromatid exchange induced by etheno-ATP derivatives in vitro. 273 26

Guinea pig endotoxicosis induced by lipopolysaccharide from Coxiella burnetii Nine Mile phase I stimulates phosphorylation of liver ribosomal protein S6, with a 50% increase at 12 h postinoculation. The responsible protein kinase (S6PK) has been partially purified from liver; its activity is independent of cyclic AMP and of Ca2+ plus phosphatidyl serine or diacylglycerol. The preparation has an apparent optimum concentration of 20 mM Mg2+, while Ca2+ and Mn2+ are each inhibitory at 2 mM. The apparent Km for ATP is 30 microM with intact ribosomes. Because of the central role of phosphorylation in metabolic regulation and a purported role of phosphorylated S6 in protein synthesis, the lipopolysaccharide-induced stimulation of S6PK suggests a significant regulatory role of such enzymes in the pathobiochemistry of Q fever infection and endotoxicosis.
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PMID:Endotoxicosis induced by Coxiella burnetii lipopolysaccharide stimulates a ribosomal protein S6 kinase: some properties of the partially purified enzyme. 280 43

Our laboratory has been comparing the activity of a water extract of cotton bract (CBE) with the isolated trachealis smooth muscle of the dog, guinea pig, and cat. CBE induced contractions that were not mediated by 5-hydroxytryptamine (5-HT), histamine, or muscarinic receptors. The active agent(s) in CBE was dialyzable (less than 14,000 molecular weight), and substantial activity was retained after low-temperature ashing. CBE potentiated contractions of dog trachealis to histamine and 5-HT and relaxation responses to isoproterenol, whereas it had no effect on responses to methacholine and KCl. In the guinea pig trachealis, CBE reduced responsiveness to KCl, potentiated relaxations to adenosine and ATP, and did not alter the responses to the remaining agents. Responses of cat trachealis to KCl and isoproterenol were potentiated by CBE, while those to 5-HT were unaffected. Neurogenic cholinergic contractile responses were potentiated by CBE in the trachealis of the dog, but not of the guinea pig, while neurogenic relaxations were potentiated by CBE in guinea pig trachealis but not in the dog trachealis. There are thus marked species differences in the acute effects of CBE on airway smooth muscle. Due to recent interest in the possible involvement of bacterial endotoxins in the etiology of byssinosis, we examined the effects of E. coli lipopolysaccharide (LPS) in guinea pig trachealis. An initial examination revealed that LPS potentiated responses to histamine, but not those to methacholine and isoproterenol. This effect vanished upon a second appraisal with a different batch of LPS. The effect of LPS in airway smooth muscle is thus, at present, equivocal.
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PMID:An overview of species differences in the effects of a water extract of cotton bract on isolated airway smooth muscle, and effects of E. coli lipopolysaccharide. 301 94


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