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At least 199 records · Page 11Linked to original sources
PubMed1997

Regulation of glutamate in cultures of human monocytic THP-1 and astrocytoma U-373 MG cells.

Glutamate, an excitatory neurotransmitter, is neurotoxic at high concentrations. Neuroglial cells, including astrocytes and microglia, play an important role in regulating its extracellular levels. Cultured human monocytic THP-1 cells increased their glutamate secretion following 18 and 68 h exposure to the inflammatory mediators zymosan, phorbol myristate acetate (PMA), lipopolysaccharide, interferon-gamma, tumor-necrosis factor-alpha and interleukin-1beta. Cultured astrocytoma U-373 MG cells increased their glutamate secretion following similar exposure to zymosan and PMA. DL-Alpha-aminopimelic acid, an inhibitor of the glutamate secretion system, reduced extracellular glutamate in both cell culture systems, while the high-affinity glutamate uptake inhibitors D-Aspartic acid, DL-threo-beta-hydroxyaspartic acid and L-trans-pyrrolidine-2,4-dicarboxylic acid increased extracellular glutamate in U-373 MG, but not THP-1 cell cultures. In co-cultures of THP-1 and U-373 MG cells, extracellular glutamate levels were increased significantly by the Alzheimer beta-amyloid peptide (1-40) and were decreased significantly by the anti-inflammatory drug dexamethasone. These data indicate that inflammatory stimuli may increase extracellular glutamate while antiinflammatory drugs decrease it.

Amyloid beta-Peptides↗
PubMed1998

Potentiation by DL-alpha-aminopimelate of the inhibitory action of a novel mGluR agonist (L-F2CCG-I) on monosynaptic excitation in the rat spinal cord.

1. Neuropharmacological actions of all the possible stereoisomers of 3',3'-difluoro-2-(carboxycyclopropyl)glycine (3',3'-difluoro-CCG) were compared with those of the corresponding 2-(carboxycyclopropyl)glycine (CCG) isomers in the isolated spinal cord of newborn rats. (2S,1'S,2'S)- and (2S,1'R,2'S)-2-(2-carboxy-3,3-difluorocyclopropyl)glycine (L-F2CCG-I and L-F2CCG-IV) were the most potent in causing depolarization, their threshold concentrations being approximately 1 microM. 2. The depolarization evoked by L-F2CCG-I (30 microM) was depressed by (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM (n=4)) to 17+/-3% of the control: this depolarizing action was not decreased by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 100 microM), and only slightly decreased by high concentrations of D-2-amino-5-phosphonopentanoic acid (D-AP5, 100 microM), suggesting that L-F2CCG-I activates mainly metabotropic glutamate receptors. 3. L-F2CCG-I preferentially depressed the monosynaptic component of the spinal reflex approximately 3 times more effectively than (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I). The depressant action of L-F2CCG-I (0.2 microM-0.7 microM) on monosynaptic excitation was antagonized by (2S,1'S,2'S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG, 0.3 mM-1 mM) and (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4, 0.3 mM). 4. DL-alpha-aminopimelate (10 and 100 microM) selectively potentiated the depression of monosynaptic excitation caused by L-CCG-I (0.2 microM) and L-F2CCG-I (0.1 microM). The actions of (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) (50 nM-0.2 microM), L-2-amino-4-phosphonobutanoic acid (L-AP4) (0.3-1 microM), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) (1-7 microM) and baclofen (0.1-0.7 microM) were unaffected by DL-alpha-aminopimelate. The threshold concentration for the potentiating actions of DL-alpha-aminopimelate was 3 microM. 5. The depolarization induced by quisqualate (3 microM, 10 s application) was increased to 115+/-2% and 137+/-5% of the control values during combined application of quisqualate with either 30 microM or 100 microM DL-alpha-aminopimelate, respectively. 6. Following the application and subsequent washout of L-F2CCG-I, DL-alpha-aminopimelate (3-100 microM) decreased the amplitude of the monosynaptic component of spinal reflexes in a concentration-dependent manner, indicating a 'priming' effect of L-F2CCG-I.

Amino Acids, Dicarboxylic↗
PubMed1993

Bacterial metabolism of 5-aminosalicylic acid: enzymic conversion to L-malate, pyruvate and ammonia.

5-Aminosalicylate (5AS) was converted to L-malate, pyruvate and ammonia by cell-free extracts from Pseudomonas sp. BN9 in the presence of glutathione. In the absence of glutathione, 5AS was oxidized to the ring-fission product cis-4-amino-6-carboxy-2-oxo-hexa-3,5-dienoate (cis-ACOHDA). Glutathione catalysed the spontaneous isomerization of cis-ACOHDA to its trans-isomer. The same reaction was catalysed by light and by acidic conditions. trans-ACOHDA was enzymically deaminated to fumarylpyruvate (trans-2,4-dioxo-5-hexenoate). The trans-ACOHDA hydrolase was induced after growth of Pseudomonas sp. BN9 with 5AS, but not after growth with acetate or nutrient broth. At the fumarylpyruvate stage, the metabolism of 5AS converged with a pathway described for the degradation of gentisate. Fumarylpyruvate was cleaved by Pseudomonas sp. BN9 to fumarate and pyruvate.

Acids↗
PubMed1999

Inhibition of uptake and release of a novel mGluR agonist (L-F2CCG-I) by anion transport blockers in the rat spinal cord.

A new metabotropic glutamate receptor (mGluR) agonist, (2S,1'S,2'S)-2-(2-carboxy-3,3-difluorocyclopropyl)glycine (L-F2CCG-I), induces a priming effect on (RS)-alpha-aminopimelate in the isolated spinal cord of newborn rats. Similar to (RS)-alpha-aminopimelate, L-glutamate (30-100 microM) neither affected spinal reflexes nor the resting membrane potentials of motoneurones, but preferentially potentiated the depression of monosynaptic excitation caused by L-F2CCG-I (0.4 microM). Following L-F2CCG-I treatment (1-2 microM), L-glutamate decreased the monosynaptic spinal reflexes in a concentration dependent manner, indicating a priming' effect of L-F2CCG-I. Thus L-glutamate is completely compatible with (RS)-alpha-aminopimelate in revealing the priming effect. An anion transport blocker, 4,4'-dinitrostilbene-2,2'-disulphonic acid (DNDS) (100 microM), markedly inhibited both the response to (RS)-alpha-aminopimelate and the induction of the L-F2CCG-I priming effect. The data suggest that L-F2CCG-I is Cl- -dependently incorporated into certain stores, and that (RS)-alpha-aminopimelate or L-glutamate must stimulate the release of L-F2CCG-I from the storage site. There were pharmacological similarities between the quisqualate and L-F2CCG-I priming effect. The physiological significance of the quisqualate or L-F2CCG-I priming is not yet established. L-F2CCG-I would be expected to be a useful pharmacological probe for elucidating the mechanism of the priming.

Amino Acids, Dicarboxylic↗
PubMed1972

Respiration and protein synthesis in Escherichia coli membrane-envelope fragments. IV. Chemical and cytological characterization and biosynthetic capabilities of fragments obtained by mild procedures.

Membrane-envelope fragments have been isolated from Escherichia coli by comparatively mild techniques. The use of DNAase, RNAase, detergents, sonication, lysozyme, and ethylenediaminetetraacetate were avoided in the belief that rather delicate, but metabolically important, associations may exist between the plasma membrane and various cytoplasmic components. The membrane-envelope fragments have been characterized in terms of their content of major chemical components as well as their electron microscope appearance. Fractions containing membrane-envelope fragments were found to possess appreciable DNA- and protein-synthesizing activities. The fragments were rich in membrane content as determined by reduced nicotinamide adenine dinucleotide (NADH) oxidase activity and deficient in soluble components as measured by NADH dehydrogenase activity. The particulate fraction obtained between 20,000 g and 105,000 g and usually considered a ribosomal fraction was rich in membrane content and had a relatively high capacity for DNA synthesis. Envelope fragments sedimenting at 20,000 g attained very high levels of incorporation of amino acids into protein.

Amino Acids↗
PubMed1973

Lysine biosynthesis in Streptomyces lipmanii: implications in antibiotic biosynthesis.

Streptomyces lipmanii produces two beta-lactam antibiotics, penicillin N and 7-(5-amino-5-carboxyvaleramido)-7-methoxycephalosporanic acid. Both antibiotics contain alpha-aminoadipic acid side chains. In similar antibiotics produced by certain fungi, the alpha-aminoadipoyl moiety is derived from an intermediate in lysine biosynthesis. Our findings indicate, however, that in S. lipmanii, lysine is synthesized via alpha, epsilon-diaminopimelic acid-an entirely different biosynthetic route. This finding suggests not only a unique mechanism for the derivation of alpha-aminoadipate, but also that the system may be particularly amenable to genetic manipulation.

Amino Acids, Diamino↗
PubMed1966

Relation between excreted lipopolysaccharide complexes and surface structures of a lysine-limited culture of Escherichia coli.

Knox, K. W. (Twyford Laboratories, London, England), Maret Vesk, and Elizabeth Work. Relation between excreted lipopolysaccharide complexes and surface structures of a lysine-limited culture of Escherichia coli. J. Bacteriol. 92:1206-1217. 1966.-The lysine-requiring mutant Escherichia coli 12408, when grown in 15 liters of defined medium containing a suboptimal amount of lysine, showed a biphasic type of growth. During a long stationary phase of 15 hr, there was a steady accumulation of diaminopimelic acid (DAP) and an antigenic complex of lipopolysaccharide (LPS) and lipoprotein; the accumulation continued unchanged until the end of the second growth phase. The rapid rate of DAP excretion suggested that it was the result of a derepressed state of a biosynthetic pathway. LPS excretion was such that the amount in the culture fluid was doubled during a period corresponding to the normal generation time for the organism; this suggested that the LPS-lipoprotein complex was a product of unbalanced growth. Surface defects were suggested by the action of lysozyme, which, in low concentrations (10 mug/ml), lysed the lysine-limited cells even in the absence of ethylenediaminetetraacetic acid, but had no effect at 10 mug/ml on cells grown with adequate lysine. Electron microscopy of cells excreting the LPS complex showed them to be surrounded by a mass of stacked leaflets and globules, some of which were bounded by triple membranes. Sections showed no lysis but changes in cell surfaces; outer layers of the walls had numerous blebs whose outer membranes were sometimes continuous with the outer triple membrane of the wall. LPS-lipoprotein probably originates from these blebs.

Animals↗
PubMed1967

Flagellated actinomycetes.

Shadowed motile elements from actinomycetes were observed with an electron microscope. Included were three strains of Actinoplanes, two of Ampullariella, two of Dermatophilus, two of Spirillospora, and four of "Nocardia" turbata. In addition, three types of previously undescribed actionmycetes were represented: (i) the C(4) group (four strains) forming substrate mycelium breaking into motile rods; (ii) strain 9-41, forming Microellobosporia-like sporangia with motile spores; and (iii) strain P(2), forming aerial hyphae releasing motile cocci when put in water. All the known chemical cell wall types of actinomycetes except the Nocardia asteroides type and the Actinomyces israeli type were represented in this array of motile actinomycetes. Motile elements were, depending on the genus, cocci, rods (often curved), or pyriform. Flagella were always in tufts (or single), never peritrichous. A relationship seems to exist between the location of the tuft and the cell wall composition. The spores of one strain of Actinoplanes were herniated, thus resembling plasmoptysis forms of bacteria.

Actinomycetales↗