Biomedical subjects

M Mangeney

Publications and source records attributed to M Mangeney.

27 records · Page 2Linked to original sources

PubMed1989

Apolipoprotein-E-gene expression in rat liver during development in relation to insulin and glucagon.

An apolipoprotein-E (apo-E) cDNA probe, cloned by immunoscreening of a lambda GT11 rat liver cDNA library, was used to further characterize the expression of the apo-E gene in rat liver during development, in relation to plasma insulin and glucagon levels. The apo-E mRNA level was low in fetus liver, then abruptly increased at birth and rose further during the suckling period. It returned to the level at birth in 10-week-old adults. These variations were paralleled with dramatic changes in plasma glucagon, which rose at birth and remained high during suckling. At the same time, the insulin/glucagon molar ratio fell. Administration of N6,O2-dibutyryl cAMP to 5-day-old rats resulted in a significant induction of liver apo-E mRNA. Moreover, liver apo-E mRNA rose in 10-h-fasted suckling rats as compared to controls, while plasma glucagon increased and the insulin/glucagon ratio decreased. Conversely, glucose feeding of suckling rats did not induce any increase in liver apo-E mRNA, the insulin/glucagon ratio was 10-fold higher than in fasted animals. Our results are consistent with liver apo-E gene expression being under the control of plasma glucagon and of the glucagon/insulin balance.

Animals↗

PubMed1989

Activation of genetically major histocompatibility complex (MHC) class II-deficient B lymphocytes.

It has been suggested that MHC class II molecules can transduce signals required for B-cell activation. Enhancement or inhibition of B-cell stimulation by anti-MHC class II molecule antibodies has likewise been reported. The study of B cells from patients with a combined immune deficiency due to a defective expression of MHC class II genes provides a useful tool for approaching the functional role of B-cell HLA class II molecules. We have thus analyzed the specific and nonspecific, cognate and noncognate B-cell activation of genetically HLA class II-deficient lymphocytes. B lymphocytes from 14 tested patients were able to synthesize RNA following stimulation with ionomycin and phorbol myristate acetate or anti-mu antibodies and with mannan, a T cell-independent polysaccharidic antigen. They were also able to synthetize DNA following the addition of ionomycin and PMA or of anti-mu antibodies in the presence of recombinant interleukin 2. Pokeweed mitogen failed to induce B-lymphocyte terminal differentiation into immunoglobulin-producing cells in the presence of normal T lymphocytes, while a combination of anti-CD2 antibodies were capable of triggering IgG synthesis. B-cell activation, whatever the condition used, did not induce HLA class II expression. Mannan-specific T cell-dependent antibody production (IgM) was detected in 6 of 14 patients. Anti-influenza virus antibody production was always found absent. These results are compatible with the hypothesis that B-cell activation events that do not require a cognate interaction with T cells can occur in the absence of HLA class II molecule expression, while the absence of HLA class II molecule expression prevents T-B cognate interaction.

Adolescent↗

PubMed1989

Direct activation of human B lymphocytes by Candida albicans-derived mannan antigen.

We have studied the activation of human resting B cells by a carbohydrate antigen, mannan, with a polymannose branched repetitive structure. Mannan has been extracted from the cell wall of the Candida albicans yeast. For this purpose, dense G0 B lymphocytes were purified from tonsils. Mannan antigen was shown to trigger B cell activation, since an increase of cell volume and RNA synthesis occurred. B cell proliferation was observed following addition of recombinant interleukin 2, but not following addition of recombinant interleukin 4 or low-molecular-weight BCGF. The B cell activation appears to be mannan-specific since B cells obtained from mannan-sensitized subjects but not from unsensitized subjects were responsive. The observation that mannan antigen can directly activate specific dense B lymphocytes can be related to the previous observation that the in vitro anti-mannan antibody production does not require a cognate T-B cell interaction.

Antigens, Fungal↗

PubMed1986

Changes of fatty acid composition of phospholipids and lipid structural order in rat liver mitochondrial membrane subsequent to galactosamine intoxication. Effect of clofibrate.

Since it has been earlier reported that D-galactosamine induces an inhibition of palmitoylcarnitine transferase I and a depletion of mitochondrial phospholipids which were both prevented by clofibrate, an evaluation of the effects of these drugs on mitochondrial fatty acid composition was made. Galactosamine does not alter the fatty acid pattern of these fatty acids whereas clofibrate induces a 2-fold increase in monounsaturated/saturated fatty acids ratio and a 10-fold decrease of the 20:4 (n - 6)/20:3 (n - 6) ratio in phosphatidylcholine. These alterations suggest an increase of delta 9-desaturation and a decrease of delta 5-desaturation. To determine whether the drug-induced changes in mitochondrial phospholipids has an effect on the physical properties of the membrane, the lipid structural order of mitochondrial preparations was studied using the lipophilic probes DPH and TMA-DPH. Mitochondrial isolated either from galactosamine- or clofibrate-treated rats showed a decrease in fluorescence polarization, indicating an overall decrease in lipid structural order. This alteration is more drastic when both drugs are administered. This phenomenon suggests drastic changes in the bulk phase of inner mitochondrial membrane lipids after treatments and could explain the altered kinetic properties of palmitoylcarnitine transferase I.

Animals↗

PubMed1986

Preventive effect of clofibrate on carnitine palmitoyltransferase I inhibition and mitochondrial membrane phospholipid depletion induced by galactosamine.

We have previously reported that a D-galactosamine injection induces a decrease of carnitine palmitoyltransferase I activity correlated with a depletion of total phospholipid content in the mitochondrial membrane. The impact of a short-term clofibrate treatment on these membrane alterations is investigated, i.e., the kinetic properties of carnitine palmitoyltransferase I, including its sensitivity to malonyl-CoA and mitochondrial membrane content of the various phospholipids. A 4-day clofibrate treatment increases by 42% the apparent Km value of carnitine palmitoyltransferase I for palmitoyl-CoA, while the sensitivity of the enzyme to malonyl-CoA appears slightly decreased. Simultaneously, the cardiolipin content is increased by 70% in the mitochondrial membrane, whereas the phosphatidylethanolamine and phosphatidylcholine contents remain almost unaffected. This 4-day clofibrate treatment prevents the inhibition of carnitine palmitoyltransferase I activity subsequent to galactosamine administration but induces an increase in the apparent Km value for palmitoyl-CoA and a decrease of the sensitivity of the enzyme to malonyl-CoA. The contents of phospholipids which are decreased by galactosamine (phosphatidylcholine, -21%; phosphatidylethanolamine, -29%; cardiolipin, -40%) regain the control values when galactosamine administration is preceded by a clofibrate treatment. The data suggest that the clofibrate treatment counteracts the inhibition of activity of carnitine palmitoyltransferase I through the maintenance of mitochondrial membrane integrity.

Acyltransferases↗

PubMed1985

Effect of D-galactosamine in vitro on [U-14C]palmitate oxidation, triacylglycerol synthesis and secretion in isolated hepatocytes.

Isolated rat hepatocytes were used to study in vitro effects of 10 mM D-galactosamine (GalN) on hepatic fatty acids metabolism. At this concentration, membrane integrity and biochemical competence (i.e., gluconeogenesis and ureogenesis) remained unaffected. Protein synthesis and secretion, as measured by the incorporation of [U-14C]leucine into total and medium protein, was significantly inhibited when incubated for more than 2 h. GalN activated the incorporation of [U-14C]palmitate into triacylglycerols and depressed its utilization in the formation of labelled ketone bodies and 14CO2. Hepatocytes isolated from fasted rats exposed to GalN in vitro did not show any variation in prelabelled triacylglycerol secretion. GalN induced a rapid inhibition of prelabelled triacylglycerol secretion by hepatocytes isolated from fed rats in which this secretion occurred to a larger extent than in hepatocytes isolated from fasted rats. The data reported here suggest that GalN induces a rise of triacylglycerol synthesis by inhibiting the palmitate oxidation pathway and a decrease of triacylglycerol secretion through an early derangement of the secretory pathway.

Animals↗

PubMed1983

Carnitine palmitoyltransferase I. Inhibition by D-galactosamine and role of phospholipids.

Palmitate oxidation by liver mitochondria from rats treated with D-galactosamine (GalN) was markedly inhibited, 3 h after administration. The mitochondrial defect responsible for this inhibition was shown to be an inhibition of the activity of palmitoylcarnitine transferase I (EC 2.3.1.21). Apparent Km of the enzyme remained unchanged whereas apparent V was reduced by 30%. Addition of 10 mM GalN did not impair the activity of palmitoylcarnitine transferase I in mitochondria isolated from normal rats. Inhibition of palmitoylcarnitine biosynthesis by GalN treatment was completely reversed by phospholipid supply. At this stage of intoxication, mitochondrial phospholipid content was decreased whereas incorporation of [14C]palmitate into phospholipids in isolated hepatocytes was drastically inhibited: the phosphatidylcholine/phosphatidylethanolamine ratio was reduced by 33%. The results obtained from these studies show that the depletion of the phospholipid membrane content could account for the altered functional activity of palmitoylcarnitine transferase I.

Acyltransferases↗

PubMed1980

Comparative study of the effect of amino acids on ethanol oxidation in isolated hepatocytes from starved and fed rats.

The effects of the various naturally occurring amino acids on ethanol oxidation in hepatocytes from 18-hrs starved and fed rats were studied. In order to minimize the non-ADH pathways and to avoid interference with the liver amino acid uptake the ethanol concentration used was 4 mM, the amino acids being added at the same concentration. In hepatocytes from starved rats, asparagine, serine, ornithine, hydroxyproline, histidine, cysteine, alanine, glycine, glutamate, glutamine, aspartate and arginine significantly increase ethanol consumption. The stimulatory effect of glutamine being much less pronounced than the asparagine one and proline being devoid of action, the influence of ammonium chloride addition on ethanol consumption in the presence of these amino acids was studied. Ammonium chloride determines an enhancement of ethanol oxidation, the results showing, contrarily to previous data, no apparent correlation between intracellular glutamate concentration and ethanol oxidation rate but rather a relation with aspartate concentration. In hepatocytes from fed rats alanine, asparagine, cysteine, glycine, hydroxyproline, ornithine and serine still increase ethanol oxidation, although to a lesser extent than in cells from starved rats. It appears that only amino acids which are precursors of either pyruvate or aspartate or glutamate are able to activate the ethanol oxidation. Pyruvate, aspartate and glutamate supply malate-aspartate shuttle components especially in cells from starved rats, pyruvate allowing direct cytosolic reoxidation of NADH in cells from fed rats as well as from starved rats. The relative strengths of the stimulatory effect could be roughly dependent on energy demand for glucose synthesis in starved rats and for urea synthesis in fed rats.

Adenosine Triphosphate↗

PubMed1979

[Effect of natural amino acids on ethanol oxidation in isolated rat hepatocytes].

The effects of the various naturally occurring amino acids on ethanol oxidation in hepatocytes from starved rats was systematically studied. In order to minimize the non ADH pathways, the ethanol concentration used was 4 mmol/litre, the amino acids being added at the same concentration. In hepatocytes from fasted rats, alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, ornithine and serine increase significantly ethanol consumption. The stimulatory effect of glutamine being much less pronounced than the asparagine one and proline being devoid of action, the influence of ammonium chloride addition on ethanol consumption in the presence of these amino acids was studied. Ammonium chloride determines an enhancement of ethanol oxidation in these conditions, the results showing no apparent correlation between intracellular glutamate concentration and ethanol oxidation rate, contrarily to previous data. In hepatocytes from fed rats, only alanine, asparagine, cysteine, glycine, hydroxyproline, ornithine and serine increase ethanol oxidation, although to a lesser extent than in cells from starved rats.

Amino Acids↗