Search PubMed⌕ Search

Biomedical subjects

G Van Den Berghe

Publications and source records attributed to G Van Den Berghe.

9 recordsLinked to original sources
PubMed2000

Metabolism and cytotoxic effects of 2-chloroadenine, the major catabolite of 2-chloro-2'-deoxyadenosine.

EHEB cells, a continuous cell line derived from a patient with B cell chronic lymphocytic leukemia (B-CLL), synthesized, when incubated with tritiated 2-chloro-2'-deoxyadenosine (CdA), labeled mono-, di-, and triphosphate ribonucleosides at a much higher rate than CdA deoxyribonucleotides. Further analysis revealed that these ribonucleotides were formed from labeled 2-chloroadenine (CAde), which contaminated commercial tritiated CdA at a proportion of 2-3%. Since CAde is the major catabolite of CdA measured in plasma after oral or intravenous administration of CdA to patients, its metabolism and in particular its potential cytotoxicity were investigated both in EHEB cells and in B-CLL lymphocytes. Phosphorylation of CAde was inhibited by adenine, indicating that its initial metabolism most probably proceeds via adenine phosphoribosyltransferase (EC 2.4.2.7). In both cell types, chloro-ATP was the major metabolite formed from CAde and its concentration increased proportionally at least up to 50 microM CAde. At high concentration, CAde metabolism was accompanied by a decrease in intracellular ATP. Cytotoxicity of CAde, evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, showed an IC(50) of 16 microM in EHEB cells and 5 microM in B-CLL lymphocytes. At cytotoxic concentrations, apopain/caspase-3 activation and high molecular weight DNA fragmentation were observed, indicating that CAde cytotoxicity results from induction of apoptosis. However, since CAde cytotoxicity requires higher concentrations than CdA, it probably does not play a role in the therapeutic effect of CdA in the treatment of hematologic malignancies.

Adenine↗
PubMed1998

Novel evidence for an ecto-phospholipid methyltransferase in isolated rat hepatocytes.

Phospholipids of isolated rat hepatocytes were labelled by preincubation with either 2 microM -methyl-14C-S-adenosylmethionine (AdoMet) or 2 microM [methyl-14C]methionine. Subsequent addition of phospholipase C to the suspension removed 95% of the radioactivity from phospholipids methylated by [methyl-14C]AdoMet within a few minutes, but was without effect on phospholipids methylated by [methyl-14C]methionine radioactivity from the latter could, nevertheless, be removed by phospholipase C after permeabilization of the cells with digitonin. The results clearly show that the methyl group of exogenous AdoMet, contrary to that of methionine, is transferred on to phospholipids located on the external face of the plasma membrane. Accordingly, pretreatment of isolated hepatocytes with trypsin prevented the methylation of phospholipids from exogenous AdoMet by 60-80%, whereas it was almost without effect when exogenous methionine was the methyl donor. Our data corroborate previous work [Bontemps and Van den Berghe (1997) Biochem. J. 327, 383-389], which indicated that AdoMet methylates hepatocyte phospholipids without penetrating the cells.

Animals↗
PubMed1997

Metabolism of exogenous S-adenosylmethionine in isolated rat hepatocyte suspensions: methylation of plasma-membrane phospholipids without intracellular uptake.

Administration of S-adenosylmethionine (AdoMet), the main biological methyl donor, has been shown to exert favourable effects on liver disorders in man and animal models. The mechanism of action of AdoMet has, however, remained elusive, mainly owing to controversies with respect to its capacity to enter intact liver cells. Incubation of isolated rat hepatocytes with 2 or 50 microM -methyl-14C-AdoMet showed that it was utilized predominantly to methylate cellular phospholipids, forming mainly phosphatidylcholine, although less than 0.2% of labelled AdoMet was found inside the cells. The concentration of neither AdoMet nor S-adenosylhomocysteine (AdoHcy), its demethylation product, was significantly elevated inside the cells. A slight elevation of intracellular AdoMet was only recorded on incubation with concentrations of AdoMet above 200 microM. AdoHcy, which does not penetrate cells, inhibited phospholipid methylation from [methyl-14C]AdoMet but not from [methyl-14C]Met. Elevation of intracellular AdoHcy by adenosine dialdehyde, an inhibitor of AdoHcy hydrolase, inhibited phospholipid methylation from [methyl-14C]Met, but virtually not at all from [methyl-14C]AdoMet. Taken together, these data indicate that exogenous AdoMet does not penetrate hepatocytes significantly but is utilized for phospholipid methylation on the outer surface of the plasma membrane.

Adenosine↗
PubMed1993

Dopamine inhibits growth hormone and prolactin secretion in the human newborn.

Dopamine is frequently used in neonatal intensive care for its vasopressor, renal vasodilating, and cardiac inotropic properties. The effect of i.v. dopamine infusion on neonatal pituitary hormone secretion is currently unknown. We observed strikingly low serum concentrations of growth hormone (GH) and prolactin (PRL) during a therapeutic, standardized, isovolumetric, partial exchange transfusion (blood sampling every 20 min for 6 h) in two polycythemic neonates requiring intensive therapy, including continuous dopamine infusion. In addition, the secretion of GH and PRL was studied in three neonates with symptomatic polycythemia (gestational age 34-38 wk; birth weight 2110-2530 g; postnatal age 10-30 h) during a partial exchange transfusion, including an intervening dopamine infusion (8 micrograms/kg/min i.v. for 2 h). The GH and PRL profiles were evaluated by deconvolution analysis. Initially, the three newborns exhibited high-amplitude, pulsatile GH secretion and continuously elevated PRL release. During the dopamine infusion, GH secretion was virtually abolished and PRL release was reduced by at least 50%. Dopamine withdrawal was associated with a rebound release of GH and PRL. Finally, serum GH and PRL concentrations were studied in nine nonpolycythemic newborns (gestational age 31-40 wk; birth weight 1680-4000 g; postnatal age 2-28 d) at the end of a prolonged dopamine infusion (3-5 micrograms/kg/min i.v. for 2-27 d). Within 2 h after dopamine withdrawal, GH and PRL levels increased a median 3-fold and 10-fold respectively. These data concord to indicate that dopamine is a potent inhibitor of GH and PRL secretion in the human newborn.

Dopamine↗
PubMed1989

Pathways and control of adenine nucleotide catabolism in anoxic rat hepatocytes.

Studies are reviewed that show that in isolated rat hepatocytes subjected to anoxia, the catabolism of AMP, leading to uric acid instead of to allantoin in normoxia, proceeds almost exclusively by deamination of AMP followed by dephosphorylation of IMP. Adenosine, which is nearly undetectable in normoxic cell suspensions, accumulates to a slight extent in anoxia. The regulatory properties of liver AMP deaminase and cytosolic IMP-GMP 5'-nucleotidase were found to provide protective mechanisms for the hepatic adenine nucleotide pool in hypoxia.

5'-Nucleotidase↗
PubMed1979

Enzyme defect in primary gout.

The rate-limiting step in the degradation of adenine nucleotides in the liver is the conversion of adenosine monophosphate (A.M.P.) to inosine monophosphate by A.M.P. deaminase, which is normally 95% inhibited. When the inhibition is released, uric acid is formed in large excess, and the biosynthesis of purines is increased. We therefore propose that congenital hyperuricaemia is caused by the presence of an abnormal A.M.P. deaminase, which is less sensitive to its physiological inhibitors. Verification of the hypothesis depends upon the availability of liver tissue from patients with congenital hyperuricaemia for kinetic analysis of A.M.P. deaminase. A call for collaboration is addressed to the medical community.

AMP Deaminase↗
PubMed1976

Treatment of ankylostomiasis with levamisole.

The authors communicate their experience in the treatment of ankylostomiase with levamisole; with a dose of 2.5 mg/kg body weight they achieved a positive result in two-thirds of the cases in a series of 119 without any toxic side effects.

Ancylostomiasis↗
PubMed1973

Effect of administration of the fructose on the glycogenolytic action of glucagon. An investigation of the pathogeny of hereditary fructose intolerance.

1. The mechanism by which the administration of fructose to patients with hereditary fructose intolerance makes them unresponsive to the hyperglycaemic action of glucagon was studied. In four patients, a 10-fold increase in the urinary excretion of cyclic AMP was induced by glucagon, but this effect was drastically decreased by the previous administration of fructose (250mg/kg). Further, the intravenous injection of 6-N,2'-O-dibutyryl cyclic AMP did not cause an increase in the blood glucose during fructose-induced hypoglycaemia. 2. The administration of a large dose of fructose (5g/kg) to mice decreased markedly both the concentration of ATP and the increase in the concentration of cyclic AMP caused by glucagon in the liver. Other ATP-depleting agents had a similar effect and a linear correlation could be drawn between the concentration of ATP and the change in cyclic AMP concentration; a half-maximal effect was obtained for a concentration of ATP close to the K(m) value of adenylate cyclase. 3. The administration of fructose to mice caused the inactivation of phosphorylase in the liver, but this effect was easily reversed by glucagon. 4. At a concentration of 10mm-fructose 1-phosphate and 1.5mm-P(i), purified liver phosphorylase a was inhibited by 70%. This inhibition appears to be a likely explanation for the unresponsiveness to glucagon of patients with hereditary fructose intolerance.

Journal Article↗