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Biomedical subjects

P Mandel

Publications and source records attributed to P Mandel.

At least 91 records · Page 5Linked to original sources
PubMed1988

ADP-ribosylation of highly purified rat brain mitochondria.

Highly purified synaptic and nonsynaptic mitochondria were prepared from rat brain, and their ADP-ribosyl transferase and NAD glycohydrolase activities were investigated. Data show that there is no significant difference in ADP-ribosyl transferase activity between these two types of subcellular preparations. However, NAD glycohydrolase activity appeared to be much higher in nonsynaptic mitochondria. The specific activity of both enzymes was investigated in the presence of the inhibitor nicotinamide or its analogue 3-aminobenzamide or other adenine nucleotides, such as ATP or ADP-ribose. The inhibitory effect of nicotinamide or 3-aminobenzamide on ADP-ribosyl transferase appears rather weak compared with their effect on NAD glycohydrolase activity. However, ADP-ribose and ATP appeared more effective in inhibiting ADP-ribosyl transferase. Our results provide evidence for the existence of ADP-ribosyl transferase activity in rat brain mitochondria. When NAD glycohydrolase was inhibited totally by nicotinamide, the transfer of ADP-ribose from NAD to mitochondrial proteins still occurred. The chain length determinations show that the linkage of ADP-ribose to mitochondrial proteins is oligomeric.

Adenosine Diphosphate Ribose↗
PubMed1988

Effect of pre- and postnatal alcohol consumption on GABA levels of various brain regions in the rat offspring.

The effect of maternal alcohol consumption during pregnancy and lactation on gamma-aminobutyric acid (GABA) levels in different rat brain regions of 3-week-old pups was investigated. There was a significant decrease in the thalamus, pons, cerebellum and hippocampus, no change in posterior colliculus, occipital cortex, temporal cortex, hypothalamus, septum or striatum and a significant increase in frontal cortex, olfactory bulbs, anterior colliculus and amygdala. These modifications could be a consequence of alterations in membrane permeability and may be related to the behavioural disorders associated with the fetal-alcohol syndrome.

Animals↗
PubMed1987

3'-5' cyclic-guanosine monophosphate increase in rat brain hippocampus after gamma-hydroxybutyrate administration. Prevention by valproate and naloxone.

An increase (123%) of cyclic GMP (cGMP) was observed in the hippocampus of the rat killed by microwave irradiation 45 min after administration of 500 mg/kg gamma-hydroxybutyrate (GHB) IP. This increase is time and dose dependent. No modification in cyclic nucleotide content was observed in striatum and in cerebellum. As the role of GHB has been implicated in neurotransmission, the fact that this compound increases cyclic GMP accumulation in hippocampus in vivo may represent a mechanism by which the actions of GHB are mediated at the cellular level. Valproate (400 mg/kg) or naloxone (10 mg/kg) pretreatment completely abolish the cGMP increase due to GHB. A GABAergic and/or opiate phenomenon may be involved in the mechanism of GHB induced increase of cGMP.

Animals↗
PubMed1987

ADP-ribosyl transferase and NAD glycohydrolase activities in rat liver mitochondria.

ADP-ribosyl transferase and NAD glycohydrolase activities have been estimated in mitochondria in mitoplasts as well as in other submitochondrial fractions. A high activity of these two enzymes was present in mitoplasts as compared to the outer membrane preparation or intermembrane compartment. Inhibitor studies provide strong evidence for the involvement of ADP-ribosyl transferase in the process of ADP-ribosylation of mitochondrial proteins. When NAD glycohydrolase was blocked by nicotinamide or 3-aminobenzamide, the incorporation of ADP-ribose into mitochondrial proteins still occurs. ADP-ribosyl transferase activity could also be detected when NAD glycohydrolase was separated by hydroxylapatite chromatography. The protein-linked ADP-ribose moiety appears to be an oligomer in mitochondria.

Animals↗
PubMed1987

Regional distribution in rat brain of tryptophan hydroxylase apoenzyme determined by enzyme-linked immunoassay.

Tryptophan hydroxylase apoenzyme was measured in 21 regions of the rat brain by a competitive enzyme-linked immunoassay (ELISA) technique using a recently developed antiserum from the sheep to this protein. Highest apoenzyme levels were found in the pineal gland and in the dorsal raphé. An insignificant level was observed in the cerebellum. In general, the distribution of tryptophan hydroxylase apoenzyme follows the distribution of serotonin previously detected by immunocytochemistry. A turnover number for tryptophan hydroxylase in a rat brain supernatant fraction of 7.5 s-1 was estimated, a value far higher than that estimated for serotonin turnover in vivo. This result confirms that serotonin biosynthesis is additionally regulated by factors other than tryptophan hydroxylase apoenzyme concentration.

Animals↗
PubMed1987

Chick brain glutamine synthetase and Mn2+-Mg2+ interactions.

Glutamine synthetase (GS) from the chick brain was purified to apparent homogeneity by ammonium sulfate fractionation followed by affinity chromatography, electrofocusing and Sephadex G-150 chromatography. The purified enzyme showed a single band on sodium dodecyl sulfate analysis in polyacrylamide gel. By sedimentation equilibrium analysis and gel electrophoresis analysis, it was shown that the enzyme has a subunit molecular weight of 45,000 and a native molecular weight of 364,000, which is consistent with an octameric structure. Sedimentation analysis in the presence of Mg2+ revealed three different forms of macromolecules corresponding respectively to a monomer, a tetramer and an octamer. Among eight cations tested (Ca2+, Co2+, Fe2+, Li+, Mg2+, Mn2+, Ni2+, Zn2+) only Co2+, Mg2+ and Mn2+ supported GS activity; the order of activatory ability was Mg2+ greater than Co2+ greater than Mn2+. The maximum activating effect of Mn2+ occurs only within a very narrow range of concentration: with an excess of cation causing strong inhibition of GS activity. For each cation, maximal GS activity occurs at a defined cation/ATP ratio. A regulatory system in which Mn2+, modulates the Mg2+ dependent GS activity, is proposed; such cation interactions may be of significance in the intracellular control of glutamine synthesis.

Animals↗
PubMed1987

Ethanolamine base exchange in astrocyte primary cultures: localization and developmental studies.

The enzymatic activities of ethanolamine base exchange (EBEE) and CDP-ethanolamine: 1,2-diacylglycerol ethanolamine phosphotransferase (EPT) were investigated during the growth of rat astrocyte primary cultures. From the 16th day, cells ceased to divide (2.0 X 10(6) cells per culture dish); the total phospholipid (PL) content increased 1.5 fold between the 16th and 24th day (0.20 to 0.30 mumol per mg protein) but the amount of ethanolamine phospholipid (28% of PL content) remained constant. Whereas the specific activity (pmol/min X mg protein) of EPT reached a plateau at 16 days in culture and remained constant (400) thereafter, that of EBEE increased up to the 19th day (190) and decreased gradually to a basal level (75) at the 24th day. EBEE activity was not detected in plasma membranes isolated from 16, 19 and 24 days astrocyte cultures. Sub-cellular fractionation and determination of EBEE specific activities showed that the 104 X 10(3) g fraction (P4) was 4.8 and 8.8 fold enriched at the 16th day and 24th day respectively as compared to the whole cell homogenate (50 and 75). The 7 X 10(3) g (P2) and 17 X 10(3) g (P3) fractions were 8.4 and 7.0 fold enriched respectively at the 19 day in culture. The percentages of the enzymatic activity in the different subcellular fractions were 30, 57.2 and 25.7 for P2 and 39.2, 2.6 and 39.8 for P4 at 16, 19 and 24 days in culture respectively. The activity remained constant in P3 (23%) and was negligible in P1 (6%). Ultrastructural studies revealed that P2 and P3 were enriched in mitochondria while P4 contained essentially microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Inhibition of mouse killing behavior by serotonin-mimetic drugs: effects of partial alterations of serotonin neurotransmission.

Rats which do not kill mice and which acquire mouse killing behavior after partial lesion of the serotonin neurotransmission, either by p-chlorophenylalanine treatment or by electrolytical lesions of dorsal and median raphe nucleus, were treated by IP injection of serotonin-mimetics. The following drugs were used: 5-methoxy-N-N-dimethyl-tryptamine and 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide, serotonin-agonists, fluoxetine and citalopram, inhibitors of serotonin uptake. All these serotonin-mimetics inhibit mouse killing behavior without apparent secondary effects. When these compounds were tested on killer rats, a stronger antimuricidal effect was observed in rats having altered serotonin neurotransmission. These results support a role for the serotoninergic supersensitivity in a model of aggressive behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Age-dependent changes of brain GABA levels, turnover rates and shock-induced aggressive behavior in inbred strains of mice.

Shock-induced aggressive behavior (SIAB) is absent or very weak in C57BL/6 (C57) mice at the age of 12 weeks while it reaches high levels at the age of 20 weeks. This age-dependent increase of aggressive responses is absent in DBA/2 (DBA) mice. Aggressive C57 mice (20 week old) are characterized by lower GABA levels in amygdala, striatum and substantia nigra than both non-aggressive C57 (12 week old) and DBA mice (12-20 week old). Concerning turnover rate, C57 mice at the age of 20 weeks show lower turnover rate values in cerebellum and raphe and higher values in septum in comparison with 12 week old mice of the same strain. These results are discussed in terms of the role of GABA function in brain areas which are involved in the control of emotionality and aggressive behavior.

Age Factors↗
PubMed1987

Glutamine synthetase and energy metabolism enzymes in cultivated chick neurons and astrocytes: modulation by serum and hydrocortisone.

Primary cultures of astroglial cells and of neurons obtained from chick embryos were grown in culture medium with and without serum added. The expression of glutamine synthetase (GS) in the cultured nerve cells was investigated immunocytochemically and biochemically. The cellular localization of GS in cerebellar tissue sections and in cerebral cortex of chick embryos was investigated by immunohistochemical staining. In tissue sections the enzyme is only present in astrocytes and their processes; neurons and their structures do not express the enzyme. In contrast, in pure neuronal primary cultures, a high level of GS was detected by biochemical and immunochemical methods. Thus, our results clearly indicate the presence of GS in pure neuronal cell cultures and its absence in this type of cells in vivo. Removal of serum from the culture medium enhanced GS levels in primary astrocyte cultures, but was without effect on GS activity in neurons. Addition of calf serum to the culture medium induces a two-fold increase of cellular lactate dehydrogenase (LDH) activity in neurons by increasing specifically the M subunit containing isoenzymes. The sensitivity of chick astroglial cells and neurons toward the GS inducing effect of hydrocortisone and modulation of its effect by serum was also investigated. Differences in the sensitivity of the two types of nerve cells in culture toward the GS inducing effect of hydrocortisone, and the effect of serum could be demonstrated.

Animals↗
PubMed1987

Immunohistochemistry of tryptophan hydroxylase in the rat brain.

An antiserum raised against tryptophan tetrahydropterine oxygen oxidoreductase was used to examine in rat brain the immunohistochemical localization of this rate-limiting enzyme catalysing the biosynthesis of serotonin. Tryptophan tetrahydropterine oxygen oxidoreductase was detected in numerous nerve cell bodies, proximal dendrites and axon varicosities or terminals corresponding to those of serotonin neurons as judged by their anatomical distribution and concomitant immunoreactivity to an antiserum against serotonin. In hypothalamus, a serotonin-containing nerve cell group previously visualized in the pars ventralis of the nucleus dorsomedialis by radioautography after serotonin uptake, and by serotonin immunohistochemistry after tryptamine loading, remained tryptophan tetrahydropterine oxygen oxidoreductase-unreactive even in rats treated with colchicine. On the other hand, a small group of tryptophan tetrahydropterine oxygen oxidoreductase-positive cells was identified in the rostrolateral portion of nucleus dorsomedialis, which could play a part in the intrinsic serotonin innervation of hypothalamus. There was no overlap between tryptophan tetrahydropterine oxygen oxidoreductase immunostaining and the cellular distribution of N-acetyl serotonin as reported in earlier studies. It is therefore likely that the synthesis of N-acetyl serotonin from tryptophan does not take place in N-acetyl serotonin-containing neurons.

Animals↗
PubMed1987

Effect of repeated convulsive seizures on brain gamma-aminobutyric acid metabolism in three sublines of mice differing by their response to acoustic stimulations.

The turnover rates and steady-state levels of gamma-aminobutyric acid (GABA) have been determined in 15 brain areas of three sublines of inbred mice differing in their susceptibility to audiogenic seizures: Rb3, which is seizure resistant; Rb2, which develops clonic seizures; and Rb1, which develops tonic-clonic seizures. In the Rb1 subline, GABA steady-state levels are lower than in the Rb3 subline in three of the 15 areas examined (cerebellum, anterior colliculus, and amygdala), whereas in the Rb2 subline, steady-state levels are either higher (posterior colliculus and hippocampus) or lower (amygdala) than in the Rb3 subline. GABA turnover rates differ in three brain areas in Rb1 (amygdala, raphe, and hypothalamus) and in a single area (amygdala) in Rb2 when compared with Rb3. Only one area has similar variations of GABA turnover rate and steady-state levels in the two susceptible sublines: the amygdala. After 2 weeks of repeated auditory stimulations (two times a day, 8,000 Hz, 100 dB), additional alterations in GABA metabolism are observed: mainly large increases in GABA turnover rates (from 40% to three- to fourfold). The Rb2 subline displays a greater number of alterations (increases of turnover rates in pons, cerebellum, anterior and posterior colliculus, amygdala, olfactory bulbs and tubercles, striatum, and frontal cortex) than the Rb1 subline (increases of turnover rates in cerebellum, posterior colliculus, olfactory tubercles, raphe, and frontal cortex and a decrease in hypothalamus). In the Rb3 subline, increases of the turnover rate in amygdala and olfactory tubercles and decreases in olfactory bulbs and hippocampus are observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1987

Effect of anticonvulsant drugs on gamma-hydroxybutyrate release from hippocampal slices: inhibition by valproate and ethosuximide.

The effects of some anticonvulsant drugs have been investigated on gamma-hydroxybutyrate release from rat hippocampal and striatal slices. Sodium valproate and ethosuximide inhibited the depolarization-evoked release of gamma-hydroxybutyrate induced by 40 mM K+. The IC50 values for these two drugs are in the concentration range of valproate and ethosuximide that exists in rat brain after administration of anticonvulsant doses to the animals. Trimethadione and pentobarbital are without significant effects. It can be concluded that the inhibition of gamma-hydroxybutyrate release, particularly that observed for hippocampus, might explain the protective effect of valproate and ethosuximide on gamma-hydroxybutyrate-induced seizures and perhaps on other kinds of epileptoid phenomenon.

Animals↗
PubMed1987

Phospholipid fatty acyl group composition in mitochondria, microsomes and plasma membranes isolated from rat astrocyte primary cultures: developmental studies.

The fatty acid composition of choline, ethanolamine and serine phospholipids (PC, PE and PS) in heavy mitochondria, light mitochondria, microsomes and plasma membranes isolated from 16-, 19- and 24-day-old cultured rat astrocytes was investigated; within this period cultures reached confluency and ceased to divide. Plasma membranes revealed a stable distribution of the major fatty acids (FA) present in PC, PE and PS. The FA pattern of PC was similar to that of PE and PS. Analysis of the FA composition of PC, PE and PS found in intracellular membranes indicates that each major FA displayed a typical variation depending on the organelle and the phospholipid studied. Schematically for both phospholipids, PC and PE, the palmitic acid content increased in most subcellular fractions between 16 and 24 days; this variation was compensated by the decrease of stearic acid. Arachidonic acid level was very low at 16 days and increased markedly up to 24 days; thus a decrease of the saturated to unsaturated FA ratio (delta:0/delta:1, 2, 4) occurred. In contrast PS, which was poor in arachidonic acid between 16 and 24 days, gave rise to delta:0/delta:1, 2, 4. These results suggest (1) a reorganisation of the phospholipid hydrophobic core in mitochondria and endoplasmic reticulum when density-dependent inhibition phenomena occurs, and (2) a 'buffering' mechanism which protects the plasma membrane from marked changes of its phospholipid FA composition.

Animals↗