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Biomedical subjects

P Mandel

Publications and source records attributed to P Mandel.

At least 199 records · Page 11Linked to original sources
PubMed1982

Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure.

When rat pancreatic polynucleosomes were poly(ADP-ribosyl)ated with purified calf thymus poly(ADP-ribose) polymerase and examined by electron microscopy, a relaxation of their native zigzag structure was observed. At high ionic strengths control nucleosomes condensed into 250-A-thick fibers, but poly(ADP-ribosyl)ated polynucleosomes did not; they showed a close resemblance to chromatin depleted of histone H1. The relaxed state of poly(ADP-ribosyl)ated polynucleosomes was also confirmed by sedimentation velocity analysis. Histone H1 was found to be the major histone acceptor of poly(ADP-ribose). Poly(ADP-ribose) linked to histone H1 did not seem to cause its dissociation from the chromatin, but it impaired significantly its effect on chromatin condensation.

Animals↗
PubMed1982

Adenosine diphosphate ribosylation of chicken-erythrocyte histones H1, H5 and high-mobility-group proteins by purified calf-thymus poly(adenosinediphosphate-ribose) polymerase.

Poly(ADP-ribosylation) of histones H1, H5 and non-histone chromosomal high-mobility-group proteins HMG 1, 2, 14 and 17 from chicken erythrocytes by purified calf thymus poly(ADP-ribose) polymerase was studied using acid/urea/Triton gel electrophoresis and autoradiography. With histone H1, besides ADP-ribosylated H1 supporting short chains of polymer, the appearance of H1 'dimer' was observed and this reaction was dependent on NAD concentration and incubation time. In addition, highly modified and/or aggregated species of histone H1 were observed. Histone H5 was slightly ADP-ribosylated at low NAD concentrations. At higher NAD concentrations or after longer incubations the formation of H5 'dimer' and of more modified forms of H5 could be observed. HMG 1 and HMG 2 were found to be ADP-ribosylated, the reaction being dependent on NAD concentration and time. Here again some discrete intermediates appeared. HMG 14 and HMG 17 were only slightly ADP-ribosylated under our experimental conditions. These results indicate that the purified DNA-independent poly(ADP-ribose) polymerase can catalyse the formation of H1 'dimer' as in nuclei and nucleosomes and that H5 and HMG proteins can also be ADP-ribosylated and produce well-defined higher complexes. These modifications of nuclear proteins may provide a means of localized conformational changes of the chromatin structure in vivo.

Animals↗
PubMed1982

A high-affinity, Na+-dependent uptake system for gamma-hydroxybutyrate in membrane vesicles prepared from rat brain.

gamma-Hydroxybutyrate (GHB) is a compared with numerous neuropharmacological properties. The discovery of its biosynthetic system, together with its endogenous repartition, have prompted its possible implication in neurotransmission. The role is also supported by the existence, reported here, of a high-affinity uptake system for GHB (Km = 46.4 microM) in both purified brain plasma membrane vesicles and in the crude mitochondrial fraction. GHB uptake is dependent on a Na+ gradient but is independent of the membrane electrical potential. Cl- and K+ can also modulate the uptake. As an approach to determine the conformation required for GHB uptake, a series of related compounds, including aryl- or alkyl- derivatives, has been examined for ability to inhibit GHB uptake. The regional distribution of uptake is also indicative of its possible physiological role, since in striatum, an area where GHB has a known pharmacological effect on dopaminergic neurons, this uptake activity is the highest.

Animals↗
PubMed1982

Activation of brain guanylate cyclase by phospholipase A2.

Various pure snake venom phospholipases A2 were used for studying their effect on guanylate cyclase activity. All the phospholipases A2 tested were found to activate guanylate cyclase from a rat brain homogenate. It was shown that particulate guanylate cyclase was especially affected. Intact glial cells incubated in presence of phospholipase A2 showed also an increased guanylate cyclase activity, demonstrating that the phospholipase effect, observed in disrupted cells, occurs also at the cellular level. These results suggest that in intact cells membrane-bound phospholipase A2 activity could be involved in the modulation of the cellular cyclic GMP content.

Animals↗
PubMed1982

Isolation of cell surface membranes from cultured C6 glioblastoma cells.

Plasma membranes were isolated from C6 glioblastoma cells by two methods. In the first method cells were treated with concanavalin A and lysed in hypotonic medium. After partial separation of plasma membranes from other cell material, the lectin was displaced with alpha-methyl-D-mannoside. In the second method untreated cells or cells iodinated in a lactoperoxidase-catalyzed reaction were homogenized in isotonic medium. Membrane fractions obtained by either homogenization procedure were further purified by rate zonal and equilibrium centrifugations into linear density gradients. Disruption of the glioblastoma cell membrane gives rise to heterogeneous assemblies of membrane fragments. Two populations of plasma membranes were isolated from untreated and from iodinated cells: a "lighter" membrane fraction characterized by relatively lower sedimentation velocity and buoyant density, and a "heavier" membrane fraction of relatively faster sedimentation velocity and higher buoyant density. Both fractions showed electrophoretic patterns similar to those of 125I-labeled cell surface proteins. Their specific (Na+ + K+)-ATPase activity was seven- to eightfold the homogenate activity (recovery, 13.1%). Both fractions were, however, still contaminated by smooth endoplasmic reticulum, as judged from the activity of NADPH-dependent cytochrome c reductase (recovery, 2.4%). It is suggested that plasma membrane fragments present in the two fractions might differ in the organization of their structures, e.g., membrane vesicle intactness and membrane orientation.

Animals↗
PubMed1982

[Frequencies of HLA-A, C and Bf antigens in schizophrenic patients originated from Alsace (author's transl)].

A comparison of the frequency of HLA-A, B, C and Bf antigens observed in a group of 75 chronic schizophrenics and in a control group of 184, all strictly from Alsace, does not carry any argument in favour of a strong genetic association between schizophrenia and the antigens studied. In effect, the modifications observed in the schizophrenic sample--decrease in the frequency of A10 and B5 antigens, and increase of A29 and BfF--are not statistically significant when the probabilities are multiplied by the number of tested antigens. These preliminary results however do not permit to exclude the possibility of an association between schizophrenia and the tested antigens.

Adolescent↗
PubMed1982

Free amino acids in the brain of ethanol treated rats.

Both acute and chronic ethanol administration to rats produce changes in free amino acids involved in nervous system function. Glutamic and aspartic acid levels are especially increased. Chronic ethanol treatment produces in addition an increase in GABA and a decrease in glutamine level. Taurine and glycine were not affected by ethanol. These variations may be explained by changes in transport phenomena and in the redox balance. They seem to correlate with the behavioural effects of acute and chronic alcohol intoxication. Tyrosine, phenylalanine and tryptophan which are related to serotonin and catecholamines formation, were found to be decreased by acute and short chronic ethanol administration.

Amino Acids↗
PubMed1981

[Adenosine-3',5'-phosphate, adenylate kinase, and cyclic AMP phosphodiesterase of the eye lens during aging].

Compared to other tissues, the level of cyclic adenosine 3',5' monophosphate (cAMP) of the whole eye lens, at all ages, is rather low. In the epithelial cell layer cAMP content is of the same order of magnitude as in brain tissue but decreases considerably with age. Adenylate cyclase activities measurable only in the epithelial cells diminishes with age. Reduction of cAMP phosphodiesterase activity is observed during aging in lens fibre cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

[Role of sialo compounds in choline uptake by synaptosomes].

Two kinetic mechanisms are responsible for the uptake of choline in Rat brain synaptosomal fractions with different affinity towards the substrate (high affinity mechanism: Km 5.1 microM, Vmax 44 pmol/mg prot/min.; low affinity mechanism: 35.7 microM, Vmax 286 pmol/mg prot/min). The treatment of synaptosomal fractions with neuraminidase (15 min. at 37 degrees C) followed by 1 min. incubation with various concentrations of [14C] choline reduces the uptake in parallel with the disappearance of the high affinity mechanism (Km 202.2 microM, Vmax 119 pmol/mg prot/min.), without influencing the synthesis of acetylcholine.

Acetylcholine↗
PubMed1981

Rat brain guanylate cyclase. Purification, amphiphilic properties and immunological characterization.

Soluble guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) has been purified to apparent homogeneity from rat brain by chromatography on Blue-Sepharose CL-6B, precipitation with (NH4)2SO4, preparative isoelectric focusing and gel-filtration on Ultrogel AcA-34. On sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis the purified enzyme showed a single band with an apparent molecular weight 59 000, when stored in buffer without glycerol and 2-mercaptoethanol. Purified enzyme has been found to be very unstable; inactivation can however be partially reversed by an endogenous heat-stable activator fraction. A monospecific antiserum obtained by immunization of rabbits was found to precipitate guanylate cyclase. This antibody also reacted with membrane-bound enzyme, indicating a close similarity to the soluble enzyme. Metal divalent cations were in general found to be strong inhibitors of the enzyme activity, though Ca2+ had no effect. ATP, CTP or UTP were shown to be competitive inhibitors of purified guanylate cyclase. Sodium nitroprusside increased cyclic GMP formation by the purified enzyme. Lysophosphatidylcholine and oleic acid, at low concentration, activated guanylate cyclase. Other unsaturated fatty acids, particularly arachidonic acid, dramatically inhibited the enzyme activity. Lipids may regulate the enzyme activity by binding to an apolar domain, as suggested by charge-shift electrophoresis. The mechanism by which guanylate cyclase is regulated in the cell appears to be a complex phenomenon. It may occur through oxidative reductive processes, and/or depend on other effectors, such as triphospho-nucleotides, divalent cations and lipid microenvironment.

Animals↗