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Biomedical subjects

P Mandel

Publications and source records attributed to P Mandel.

At least 109 records · Page 6Linked to original sources
PubMed1987

[ADP ribosylation: knowledge and perspectives].

Polyadenosine diphosphate ribose (polyADPR) and polyADPR-polymerase (polyADPR-P) were discovered in our laboratory in 1966. Then it has been demonstrated that the enzyme and the polymer exist in all eukaryotic cells and catalyze a transfer of ADP-ribose moieties to proteins. Ever increasing evidence favours an involvement of the enzyme through protein ADP-ribosylation in DNA duplication, transcription and repair. Recently the existence of poly or oligo ADP-ribosyl transferases were demonstrated in mitochondria and cytoplasmic particles which carry messenger RNA (mRNP). The nuclear DNA dependent ADPR polymerase produces ADP-ribosylation of a great number of nuclear proteins, resulting in polynucleosome relaxation and modulation of several nuclear enzymes activity. The mRNP ADP-ribosyl transferase may be implicated in derepression of the repressed mRNA. Since 1968 enzymes producing monoADP-ribosylation were discovered in several bacterial toxins and since 1975 in animal tissues. Nicotinamide and its structural analogue: 3-aminobenzamide inhibits ADP-ribosylation and by thus causing inhibition of cell proliferation. Some effects of these inhibitors on cell proliferation are reported and the possible use in tumoral growth as an adjuvant of antimitotics is discussed. Thus ADP-ribosylation appears to be a basic multifunctional event with multiple target sites, some of which are of interest for antitumor therapy.

ADP Ribose Transferases↗
PubMed1986

The nature of DT-diaphorase (EC 1.6.99.2) activity in plasma membrane of astrocytes in primary cultures.

This is the confirmation of an earlier indication (Mersel, M., Malviya, A.N., Hindelang, C. and Mandel, P. (1984) Biochim. Biophys. Acta 778, 144-154) that the plasma membrane of astrocytes in primary cultures is endowed with DT-diaphorase (EC 1.6.99.2) activity. It is observed that the NADPH-2,6-dichloroindophenol diaphorase activity found in the isolated plasma membrane is not inhibited by dicoumarol. DT-diaphorase-type activity is also observed on the cell surface employing dichloroindophenol as external electron acceptor and it is found to be a dicoumarol-sensitive NADH dehydrogenase.

Animals↗
PubMed1986

Effects of the potentiation of the GABAergic neurotransmission in the olfactory bulbs on mouse-killing behavior.

Intra olfactory bulb administration of three classes of GABA-mimetics (GABAa agonists, inhibitors of reuptake, inhibitors of GABA degradation) clearly inhibit mouse-killing behavior, without sedation. A linear correlation is observed between GABA levels increase in the olfactory bulbs and muricidal inhibition following local injection of valproic acid and gamma-vinyl GABA, two GABA-T inhibitors; the differences observed between these two compounds may be due to the differences in their mechanism of action on GABA-T activity and to the different pool of GABA on which they act. No diffusion to extra bulbar sites were observed after local administration of gamma-vinyl GABA. This evidence suggests an inhibitory role of GABA from olfactory bulbs in the modulation of mouse-killing behavior.

Aggression↗
PubMed1986

A new immunization procedure for obtention of anti-leucine-enkephalin antibodies. Part II. Effects of olfactory bulb removal on pro-enkephalin related peptides in rat brain.

Bilateral Olfactory Bulb Removal (OBR) induced both complex behavioral alterations and a decrease of many neurotransmitter levels. We studied brain levels of the pro-enkephalin related peptides 45 days after OBR. Opioid levels were studied using three different highly specific antisera exhibiting very high affinities in radioimmunoassays in striatum, hypothalamus, hypophysis, brain stem and cortex. Methionine enkephalin levels increase significantly in striatum (42%), hypophysis (94%) and hypothalamus (25%) and non-significantly in the other areas. Leucine-enkephalin levels tended to increase in all dissected structures but a significant increase only occurred in striatum (42%). Octapeptide levels (Methionine-enkephalin-Arg-Gly-Leu) significantly increase in striatum (22%) and decrease in hypophysis (97%) and in brain stem (76%). All these results are partially consistent with the decrease of opiate binding described previously after OBR and suggest a complex imbalance in neurotransmitters after such a sensorial deprivation. It is suggested that the modifications of enkephalinergic neurotransmission might be related to the stressful state induced by OBR.

Animals↗
PubMed1986

Effects of naloxone administration on attack by castrated male mice on lactating intruders.

The effect of the narcotic antagonist naloxone (a mu blocker at low doses) on the attack displayed by castrated male mice towards lactating intruders was investigated. Naloxone at doses of 1 mg and 2 mg/kg decreased attacks an effect which was also evident to a lesser extent at 0.75 mg/kg. These findings suggest a role for endogenous opiates in the expression of this form of aggression although one must warn that naloxone at some of the higher doses used here can influence kappa and delta receptors as well as gabaergic activity. The interrelationships between endogenous opioids, gabaergic neurotransmission and gonadal hormones in the regulation of this attack response are discussed.

Aggression↗
PubMed1986

NAD+ glycohydrolase of the plasma membrane prepared from glial and neuronal cells.

NAD+ glycohydrolase (EC 3.2.2.5) activity was detected in the plasma membrane prepared from the primary culture of rat astrocytes. The enzyme has a broad optimum pH range. From the kinetic analysis, a Michaelis constant of 91.2 microM and a maximum velocity of 0.785 mumol/min/mg protein were obtained. ADPribose exhibited a competitive inhibition with respect to NAD. The inhibition by nicotinamide was shown to be of a non-competitive type. ATP and GTP were found to be competitive inhibitors. NAD+ glycohydrolase activity was not detected in the plasma membrane prepared from the primary culture of neuronal cells of chick embryos.

Adenosine Diphosphate Ribose↗
PubMed1986

Surface glycosyltransferase activities during development of neuronal cell cultures.

Neurons in culture obtained from dissociated cerebral hemispheres of 8-day-old chick embryos showed measurable activities of galactosyl-, fucosyl-, and sialyl-transferases at the external surface of their plasma membrane. Important changes in these activities were observed during cell proliferation and maturation, in particular the surface fucosyltransferase activity, and/or the amount of intracellular fucosylated acceptors increased during synaptogenesis, between 3 and 5 days in culture (d.i.c.). A sodium dodecyl sulfate radioelectrophoretic analysis of the fucosylated neuronal acceptors labelled with [14C]fucose showed, during synaptogenesis, the high labelling of two protein bands of 116 and 50 X 10(3) daltons. The fucosylation of glycoconjugates occurred preferentially, in neurons, upon glycoproteins whereas in glial cell cultures glycolipids were more fucosylated. The reasons for such a difference are not yet understood but the results suggest that the surface fucosyltransferase activity and fucosylated proteins in particular may play a role during the synaptogenesis of neurons in culture.

Animals↗
PubMed1986

Brain gamma-aminobutyric acid turnover rates after spontaneous chronic ethanol intake and withdrawal in discrete brain areas of C57 mice.

The effect of 4 weeks of spontaneous chronic ethanol intake in drinking water and then ethanol withdrawal on the gamma-aminobutyric acid (GABA) steady-state levels and turnover rates was investigated in 15 brain areas of C57 Bl/6J alcohol-preferring mice. These mice did not display typical ethanol withdrawal convulsions. There was no statistically significant difference in the brain GABA steady-state levels among the control group, chronic ethanol-treated mice, and mice after ethanol withdrawal. In contrast, chronic ethanol treatment induced significant variations in GABA turnover rate, as measured by gabaculine-induced accumulation of GABA, in eight of 15 areas examined versus a decrease in seven brain areas [cerebellum (-29%), amygdala (-28%), olfactory tubercles (-24%), septum (-24%), striatum (-53%), frontal cortex (-21%), and hippocampus (-24%)]; an increase in turnover rate in the posterior colliculus (100%) was observed. At 26 h after ethanol withdrawal, in the seven areas in which GABA turnover rate decreased after spontaneous chronic ethanol intake, a return to the initial control value was observed; in the posterior colliculus, the turnover rate did not change, remaining higher than the control value. This persisting alteration of GABA turnover rate may be related to the absence of the ethanol withdrawal syndrome in the C57 mouse strain.

Animals↗
PubMed1986

[Correlation between the steady state and turnover of gamma-aminobutyric acid during brain maturation in mice].

In 2 inbred strains of mice (C57Bl/6J, DBA/2J) in 15 areas, the in vivo GABA turnover rates are significantly correlated with the GABA steady-state levels in 21 day-old mice. In 3 month-old mice the correlation stands only in some areas, the same ones in the 2 strains: olfactory bulbs, frontal cortex, septum, amygdala, hypothalamus, hippocampus, cerebellum. Moreover, the turnover rates decrease sharply with age.

Aging↗
PubMed1985

Characterization of the poly(ADP-ribose) polymerase associated with free cytoplasmic mRNA-protein particles.

Poly(ADP-ribose) polymerase associated with free cytoplasmic messenger ribonucleoprotein particles (mRNP) has been characterized in mouse plasmacytoma. This cytoplasmic enzyme undergoes auto-ADP-ribosylation and has a similar molecular weight and common antigenic sites with the chromatin bound poly(ADP-ribose) polymerase in spite of its DNA independency. The free mRNP poly(ADP-ribose) polymerase is released from the particle only by high saline concentrations (0.7 M KCl) and the dissociated enzyme expresses a higher activity. The treatment of free mRNP by RNase A stimulates the poly(ADP-ribose) polymerase activity. Partial destruction of mRNP by high saline concentration or mRNA digestion unmasks new protein sites for ADP-ribosylation. In view of the changes that occur in the free mRNP structure to permit mRNA translation, a possible role of poly(ADP-ribosylation) as an important post-synthetic modification of some of the mRNP proteins is discussed.

Animals↗
PubMed1985

Evidence for a role of high Km aldehyde reductase in the degradation of endogenous gamma-hydroxybutyrate from rat brain.

gamma-Hydroxybutyrate (GHB) is a putative neurotransmitter in brain. We have already demonstrated that it is transformed into gamma-aminobutyrate (GABA) by rat brain slices incubated under physiological conditions. This conversion occurs via a GABA-transaminase reaction. Therefore, succinic semialdehyde, the oxidative derivative of GHB, appears to be the primary catabolite of GHB degradation. Apparently, the kinetic characteristics and pH optimum of GHB dehydrogenase (high Km aldehyde reductase) in vitro do not favor a role for this enzyme in endogenous brain GHB oxidation. However, in the presence of glucuronate, glutamate, NADP and pyridoxal phosphate, pure GHB dehydrogenase, coupled to purified GABA-transaminase does produce GABA from GHB at an optimum pH close to the physiological value and with a low Km for GHB.

4-Aminobutyrate Transaminase↗
PubMed1985

Valproate increases diazepam impregnation selectively in CNS of the rat after subchronic administration.

Valproate-Diazepam association is not unusual in the treatment of epilepsies. The present paper investigates in an experimental study the effect of sodium valproate (VPA) on the regional cerebral level of diazepam (DZP), and the relationship with plasma or erythrocytes amounts after subchronic administration. The VPA addition increases the DZP levels in peripheral and central compartments. The results shows a linear correlation between the drug concentration in all areas studied and the plasmatic or erythrocytic amounts during the CNS - impregnation phase. The VPA influence is greater in the CNS where the DZP impregnation is selectively increased, specially in cortex and cerebellum.

Analysis of Variance↗
PubMed1985

Circannual variations of GABA content in cytosolic and crude synaptosomal fractions in some brain areas of the European hamster.

In the European hamster, Cricetus cricetus, a common hibernator, over a year, the gamma-aminobutyric acid (GABA) content has been followed, in the cytosolic and crude synaptosomal fractions of the olfactory bulbs, hypothalamus and cerebellum. In these 3 areas, the GABA content shows circannual variations of endogenous origin: in this period, in both fractions two peaks can be observed, at the beginning of spring and in autumn. These circannual variations do not follow the circannual variation of food intake or body weight.

Animals↗
PubMed1985

Tryptophan 5-hydroxylase. Rapid purification from whole rat brain and production of a specific antiserum.

Tryptophan 5-hydroxylase (EC 1.14.16.4; L-tryptophan tetrahydropteridine: oxygen oxidoreductase) was purified to electrophoretic homogeneity from whole brain supernatant using the following steps: pteridine-argarose affinity chromatography, hydrophobic and finally hydroxyapatite chromatography. Exogenous catalase was necessary throughout most of the purification procedure in order to protect the enzyme against inactivation. The iron chelator desferrioxamine at a concentration of 10 microM or higher brought about an irreversible loss of enzyme activity of a partially purified preparation containing an excess of catalase, whereas this same chelator at a lower concentration afforded considerable protection of the enzyme's activity during the final purification stage despite the quasi-total absence of catalase and the presence of an excess of ferrous iron. Antiserum raised in the rabbit to purified tryptophan 5-hydroxylase appears to be monospecific for the enzyme after immunoadsorption of anti-catalase antibodies which were present due to the trace of catalase which remained in the final enzyme preparation.

Animals↗