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)

Escherichia coli O127:B8 lipopolysaccharide (LPS), prepared by the Westphal procedure, caused a marked decrease in the activities of mitochondrial malate dehydrogenase, succinate dehydrogenase, and adenylate kinase in African green monkey kidney (Vero) cells and primary cultures of mouse liver cells within 2 h after exposure to 10 micrograms of LPS/ml of culture medium. These three enzyme activities leaked into the supernatant fraction, and cytochrome oxidase activity was lost from the mouse liver mitochondrial particulate fraction within 45 min after exposure to 10 micrograms of LPS/mg of protein. Loss malate dehydrogenase activity from isolated mitochondria was also accelerated by LPS from E. coli O26:B6 (Boivin preparation) or Salmonella typhosa O901 (Westphal preparation), and by lipid A from Salmonella minnesota or Shigella sonnei. In addition, LPS and lipid A inhibited state 3 respiration by isolated mitochondria with attendant loss of respiratory control, but adenosine 5'-diphosphate/O ratios were relatively unchanged. Impaired mitochondrial function is an early event after exposure to biologically relevant amounts of LPS or lipid A.
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PMID:Action of bacterial endotoxin and lipid A on mitochondrial enzyme activities of cells in culture and subcellular fractions. 11 91

Cytochrome oxidase variants of the bacterial fish pathogen, Aeromonas salmonicida, were characterized for genetic and molecular homology with cytochrome oxidase-positive isolates that typically induce furunculosis in salmonids. Protein and lipopolysaccharide moieties of the cytochrome oxidase-negative variants were similar to their typical counterparts, based on sodium-dodecyl-sulfate polyacrylamide gel electrophoresis. Pathogenicity of aberrant isolates to brook trout (Salvelinus fontinalis) was similar to typical cytochrome oxidase-positive isolates. Colorimetric deoxyribonucleic acid (DNA) hybridization in 96-well microplates yielded homology values greater than 82.5% for typical aberrant A. salmonicida isolates when photobiotinylated DNA for reference A. salmonicida 3.101 was used as a probe. The only variation of these isolates from typical A. salmonicida was a negative cytochrome oxidase reaction.
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PMID:Molecular and genetic characterization of cytochrome oxidase-negative Aeromonas salmonicida isolated from coho salmon (Oncorhynchus kisutch). 133 20

A technique is described for the quantitative recovery of monocytes from horse blood by means of flotation on dense albumin solutions. Monocytes are concentrated in a surface pellicle along with a few lymphocytes which are then removed when the monocytes adhere to a glass surface. The in vitro cultivation of homogeneous populations of monocytes results in an increase in (a) cell size, (b) number of mitochondria, and (c) phase-dense granules of the centrosphere. The phase-dense granules are osmiophilic and acid phosphatase positive. Quantitative biochemical analysis during cultivation have revealed increased levels of cytochrome oxidase, acid phosphatase, arylsulfatase, and BPN hydrolase. In addition, glucose utilization and lactic acid production are stimulated under the same conditions. The uptake of both bacteria and colloidal gold is stimulated during in vitro cultivation. The phagocytic activity of cultured monocytes may be enhanced by a purified bacterial lipopolysaccharide. These data are consistant with the in vitro maturation of monocytes to macrophages, a cell with greater metabolic and functional potentional.
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PMID:The isolation and selected properties of blood monocytes. 428 46

In this study we have investigated the mechanisms leading to mitochondrial damage in cultured neurons following sustained exposure to nitric oxide. Thus, the effects upon neuronal mitochondrial respiratory chain complex activity and reduced glutathione concentration following exposure to either the nitric oxide donor, S-nitroso-N-acetylpenicillamine, or to nitric oxide releasing astrocytes were assessed. Incubation with S-nitroso-N-acetylpenicillamine (1 mM) for 24 h decreased neuronal glutathione concentration by 57%, and this effect was accompanied by a marked decrease of complex I (43%), complex II-III (63%), and complex IV (41%) activities. Incubation of neurons with the glutathione synthesis inhibitor, L-buthionine-[S,R]-sulfoximine caused a major depletion of neuronal glutathione (93%), an effect that was accompanied by a marked loss of complex II-III (60%) and complex IV (41%) activities, although complex I activity was only mildly decreased (34%). In an attempt to approach a more physiological situation, we studied the effects upon glutathione status and mitochondrial respiratory chain activity of neurons incubated in coculture with nitric oxide releasing astrocytes. Astrocytes were activated by incubation with lipopolysaccharide/interferon-gamma for 18 h, thereby inducing nitric oxide synthase and, hence, a continuous release of nitric oxide. Coincubation for 24 h of activated astrocytes with neurons caused a limited loss of complex IV activity and had no effect on the activities of complexes I or II-III. However, neurons exposed to astrocytes had a 1.7-fold fold increase in glutathione concentration compared to neurons cultured alone. Under these coculture conditions, the neuronal ATP concentration was modestly reduced (14%). This loss of ATP was prevented by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine. These results suggest that the neuronal mitochondrial respiratory chain is damaged by sustained exposure to nitric oxide and that reduced glutathione may be an important defence against such damage.
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PMID:Nitric oxide-mediated mitochondrial damage: a potential neuroprotective role for glutathione. 893 84

The aim of this study is to clarify the influence of nitric oxide (NO) in cerebral circulation during endotoxemia. Two groups of 24 mongrel dogs (N = 12 each) received saline 1 ml.kg-1.h-1 or endotoxin (lipopolysaccharide, LPS) 500 ng.kg-1.h-1 for 3 hours. To determine changes of NO in the systemic and cerebral circulation, we measured NOx (NO2-/NO3-) in the femoral artery and superior sagittal sinus as metabolites of NO using the Griess method. We also measured the concentrations of cerebral oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), total hemoglobin (total Hb) and cytochrome aa3 (Cytaa3) using near-infrared laser spectroscopy. Changes in cerebral blood volume were evaluated from the total Hb. NOx in systemic and cerebral circulation increased significantly after infusion of LPS. Therefore, the increased production of NO in cerebral circulation was consistent with increase of cerebral blood volume. In conclusion, it seems reasonable to assume that increased cerebral blood volume may result from increased production of cerebral NO during endotoxemia.
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PMID:[Influence of nitric oxide on cerebral hemodynamics during endotoxemia in dogs]. 1003 85

Microglial activation, oxidative stress, and dysfunctions in mitochondria, including the reduction of cytochrome oxidase activity, have been implicated in neurodegeneration. The current experiments tested the effects of reducing cytochrome oxidase activity on the ability of microglia to respond to inflammatory insults. Inhibition of cytochrome oxidase by azide reduced oxygen consumption and increased reactive oxygen species (ROS) production but did not affect cell viability. Azide also attenuated microglial activation, as measured by nitric oxide (NO.) production in response to lipopolysaccharide (LPS). It is surprising that the inhibition of cytochrome oxidase also diminished the activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a Krebs cycle enzyme. This reduction was exaggerated when the azide-treated microglia were also treated with LPS. The combination of the azide-stimulated ROS and LPS-induced NO. would likely cause peroxynitrite formation in microglia. Thus, the possibility that KGDHC was inactivated by peroxynitrite was tested. Peroxynitrite inhibited the activity of isolated KGDHC, nitrated tyrosine residues of all three KGDHC subunits, and reduced immunoreactivity to antibodies against two KGDHC components. Thus, our data suggest that inhibition of the mitochondrial respiratory chain diminishes aerobic energy metabolism, interferes with microglial inflammatory responses, and compromises mitochondrial function, including KGDHC activity, which is vulnerable to NO. and peroxynitrite that result from microglial activation. Thus, activation of metabolically compromised microglia can further diminish their oxidative capacity, creating a deleterious spiral that may contribute to neurodegeneration.
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PMID:Metabolic impairment induces oxidative stress, compromises inflammatory responses, and inactivates a key mitochondrial enzyme in microglia. 1021 72

Microglial activation is common in several neurodegenerative disorders. In the present study, we used the murine BV-2 microglial cell line stimulated with gamma-interferon and lipopolysaccharide to gain new insights into the effects of endogenously produced NO on mitochondrial respiratory capacity, iron regulatory protein activity, and redox-active iron level. Using polarographic measurement of respiration of both intact and digitonin-permeabilized cells, and spectrophotometric determination of individual respiratory chain complex activity, we showed that in addition to the reversible inhibition of cytochrome-c oxidase, long-term endogenous NO production reduced complex-I and complex-II activities in an irreversible manner. As a consequence, the cellular ATP level was decreased in NO-producing cells, whereas ATPase activity was unaffected. We show that NO up-regulates RNA-binding of iron regulatory protein 1 in microglial cells, and strongly reduces the labile iron pool. Together these results point to a contribution of NO derived from inflammatory microglia to the misregulation of energy-producing reactions and iron metabolism, often associated with the pathogenesis of neurodegenerative disorders.
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PMID:Impact of endogenous nitric oxide on microglial cell energy metabolism and labile iron pool. 1206 70

Nitric oxide (NO), in excess, behaves as a cytotoxic substance mediating the pathological processes that cause neurodegeneration. The NO-induced dopaminergic cell loss causing Parkinson's disease (PD) has been postulated to include the following: an inhibition of cytochrome oxidase, ribonucleotide reductase, mitochondrial complexes I, II, and IV in the respiratory chain, superoxide dismutase, glyceraldehyde-3-phosphate dehydrogenase; activation or initiation of DNA strand breakage, poly(ADP-ribose) synthase, lipid peroxidation, and protein oxidation; release of iron; and increased generation of toxic radicals such as hydroxyl radicals and peroxynitrite. NO is formed by the conversion of L-arginine to L-citrulline by NO synthase (NOS). At least three NOS isoforms have been identified by molecular cloning and biochemical studies: a neuronal NOS or type 1 NOS (nNOS), an immunologic NOS or type 2 NOS (iNOS), and an endothelial NOS or type 3 NOS (eNOS). The enzymatic activities of eNOS or nNOS are induced by phosphorylation triggered by Ca(2+) entering cells and binding to calmodulin. In contrast, the regulation of iNOS seems to depend on de novo synthesis of the enzyme in response to a variety of cytokines, such as interferon-gamma and lipopolysaccharide. The evidence that NO is associated with neurotoxic processes underlying PD comes from studies using experimental models of this disease NOS inhibitors can prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. Furthermore, NO fosters dopamine depletion, and the said neurotoxicity is averted by nNOS inhibitors such as 7-nitroindazole working on tyrosine hydroxylase-immunoreactive neurons in substantia nigra pars compacta. Moreover, mutant mice lacking the nNOS gene are more resistant to MPTP neurotoxicity when compared with wild-type littermates. Selegiline, an irreversible inhibitor of monoamine oxidase B, is used in PD as a dopaminergic function-enhancing substance. Selegiline and its metabolite, desmethylselegiline, reduce apoptosis by altering the expression of a number of genes, for instance, superoxide dismutase, Bcl-2, Bcl-xl, NOS, c-Jun, and nicotinamide adenine nucleotide dehydrogenase. The selegiline-induced antiapoptotic activity is associated with prevention of a progressive reduction of mitochondrial membrane potential in preapoptotic neurons. As apoptosis is critical to the progression of neurodegenerative disease, including PD, selegiline or selegiline-like compounds to be discovered in the future may be efficacious in treating PD.
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PMID:Peroxynitrite and mitochondrial dysfunction in the pathogenesis of Parkinson's disease. 1288 Apr 86

Neufeld, Harold A. (U.S. Army Biological Laboratories, Fort Detrick, Frederick, Md.), Ronald L. Coleman, and Joseph S. Zannucci. Respiratory inhibitor from Serratia marcescens. J. Bacteriol. 85:614-618. 1963.-A substance was obtained from Serratia marcescens in conjunction with lipopolysaccharide that is a potent inhibitor of mammalian succinoxidase activity. It was determined that the purified lipopolysaccharide is not an in vitro inhibitor of the succinoxidase system. The inhibitor has no effect on succinic dehydrogenase or cytochrome oxidase but apparently exerts its effect on some portion of the electron-transport chain between the dehydrogenase and cytochrome c.
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PMID:RESPIRATORY INHIBITOR FROM SERRATIA MARCESCENS. 1404 39

Bordetella pertussis, B. bronchiseptica, B. parapertussis(hu), and B. parapertussis(ov) are closely related respiratory pathogens that infect mammalian species. B. pertussis and B. parapertussis(hu) are exclusively human pathogens and cause whooping cough, or pertussis, a disease that has resurged despite vaccination. Although it most often infects animals, infrequently B. bronchiseptica is isolated from humans, and these infections are thought to be zoonotic. B. pertussis and B. parapertussis(hu) are assumed to have evolved from a B. bronchiseptica-like ancestor independently. To determine the phylogenetic relationships among these species, housekeeping and virulence genes were sequenced, comparative genomic hybridizations were performed using DNA microarrays, and the distribution of insertion sequence elements was determined, using a collection of 132 strains. This multifaceted approach distinguished four complexes, representing B. pertussis, B. parapertussis(hu), and two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Of the two B. bronchiseptica complexes, complex IV was more closely related to B. pertussis. Of interest, while only 32% of the complex I strains were isolated from humans, 80% of the complex IV strains were human isolates. Comparative genomic hybridization analysis identified the absence of the pertussis toxin locus and dermonecrotic toxin gene, as well as a polymorphic lipopolysaccharide biosynthesis locus, as associated with adaptation of complex IV strains to the human host. Lipopolysaccharide structural diversity among these strains was confirmed by gel electrophoresis. Thus, complex IV strains may comprise a human-associated lineage of B. bronchiseptica from which B. pertussis evolved. These findings will facilitate the study of pathogen host-adaptation. Our results shed light on the origins of the disease pertussis and suggest that the association of B. pertussis with humans may be more ancient than previously assumed.
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PMID:Bordetella pertussis, the causative agent of whooping cough, evolved from a distinct, human-associated lineage of B. bronchiseptica. 1638 2


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