References of "Bettendorff, Lucien"
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See detailBisindole alkaloids from Strychnos guianensis are effective antagonists of nicotinic acetylcholine receptors in cultured human TE671 cells
Wins, Pierre; Margineanu, Ilca; Penelle, Jacques et al

in Naunyn-Schmiedeberg's Archives of Pharmacology (2003), 367(3), 253-259

Several mono- and bisindole quaternary alkaloids isolated from the stem bark of Strychnos guianensis have recently been shown to be effective blockers of neuromuscular transmission in mice. In this study ... [more ▼]

Several mono- and bisindole quaternary alkaloids isolated from the stem bark of Strychnos guianensis have recently been shown to be effective blockers of neuromuscular transmission in mice. In this study, we used a human clonal cell line (TE671) expressing muscle-type nicotinic acetylcholine receptors. The agonist carbamylcholine activated a receptor-mediated Rb-86(+) efflux and this activation was antagonized by the indole alkaloids, the most active being bisindole bisquaternary compounds. The most effective antagonist, guiachrysine, had an IC50 around 0.43 muM in the presence of 0.5 mM carbamylcholine, compared to 0.16 muM for d-tubocurarine, the most potent curarizing alkaloid. Guiaflavine and 5',6'-dehydroguiaflavine were slightly less effective. Monoindole compounds were 10 to 100 times less potent than bisindole alkaloids. Kinetic analysis showed that the inhibition of the carbamylcholine-dependent Rb-86(+) efflux by guiaflavine was of mixed competitive and uncompetitive type. The competitive component (K-I = 0.21 muM) is presumably due to binding at the acetylcholine site, while the uncompetitive component (K'(I) = 0.92 muM) may be due to open channel block. [less ▲]

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See detailA general method for the chemical synthesis of gamma-P-32-labeled or unlabeled nucleoside 5 '-triphosphates and thiamine triphosphate
Bettendorff, Lucien ULg; Nghiem, Hoang O; Wins, Pierre et al

in Analytical Biochemistry (2003), 322(2), 190-197

Several methods for the chemical synthesis of gamma-P-32-labeled and unlabeled nucleoside 5'-triphosphates and thiamine triphosphate (ThTP) have been described. They often proved unsatisfactory because of ... [more ▼]

Several methods for the chemical synthesis of gamma-P-32-labeled and unlabeled nucleoside 5'-triphosphates and thiamine triphosphate (ThTP) have been described. They often proved unsatisfactory because of low yield, requirement for anhydrous solvents, procedures involving several steps or insufficient specific radioactivity of the labeled triphosphate. In the method described here, all these drawbacks are avoided. The synthesis of [gamma-P-32]TbTP was carried out in one step, using 1,3-dicyclohexyl carbodiimide as condensing agent for thiamine diphosphate and phosphoric acid in a dimethyl sulfoxide/pyridine solvent mixture. Anhydrous solvents were not required and the yield reached 90%. After purification, [gamma-P-32]ThTP had a specific radioactivity of 11 Ci/mmol and was suitable for protein phosphorylation. The method can also be used for the synthesis Of [gamma-P-32]ATP of the desired specific radioactivity. It can easily be applied to the synthesis of unlabeled ThTP or ribo- and deoxyribonucleoside 5'-triphosphates. In the latter case, inexpensive 5'-monophosphate precursors can be used as reactants in a 20-fold excess of phosphoric acid. Deoxyribonucleoside 5'-triphosphates were obtained in 6 h with a yield of at least 70%. After purification, the nucleotides were found to be suitable substrates for Taq polymerase during polymerase chain reaction cycling. Our method can easily be scaled up for industrial synthesis of a variety of labeled and unlabeled triphosphoric derivatives from their mono- or diphosphate precursors. (C) 2003 Elsevier Inc. All rights reserved. [less ▲]

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See detailMolecular characterization of a specific thiamine triphosphatase widely expressed in mammalian tissues
Lakaye, Bernard ULg; Makarchikov, Alexander F; Antunes, Adelio F et al

in Journal of Biological Chemistry (2002), 277(16), 13771-13777

Thiamine triphosphate (ThTP) is found at low concentrations in most animal tissues, and recent data suggest that it may act as a phosphate donor for the phosphorylation of some proteins. In the mammalian ... [more ▼]

Thiamine triphosphate (ThTP) is found at low concentrations in most animal tissues, and recent data suggest that it may act as a phosphate donor for the phosphorylation of some proteins. In the mammalian brain, ThTP synthesis is rapid, but its steady-state concentration remains low, presumably because of rapid hydrolysis. In this report we purified a soluble thiamine triphosphatase (ThTPase; EC 3.6.1.28) from calf brain. The bovine ThTPase is a 24-kDa monomer, hydrolyzing ThTP with virtually absolute specificity. Partial sequence data obtained from the purified bovine enzyme by tandem mass spectrometry were used to search the GenBank(TM) data base. A significant identity was found with only one human sequence, the hypothetical 230-amino acid protein MGC2652. The coding regions from human and bovine brain mRNA were amplified by reverse transcription-PCR, cloned in Escherichia coli, and sequenced. The human open reading frame was expressed in E. coli as a GST fusion protein. Transformed bacteria had a high isopropyl-beta-D-thiogalactopyranoside-inducible ThTPase activity. The recombinant ThTPase had properties similar to those of human brain ThTPase, and it was specific for ThTP. The mRNA was expressed in most human tissues but at relatively low levels. This is the first report of a molecular characterization of a specific ThTPase. [less ▲]

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See detailRelevance of molecular biology to Psychopharmacology
Bettendorff, Lucien ULg

Conference (2002)

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See detailStudy of the role of ionogenic amino-acid residues in catalytic activity of thiamine triphosphatase from bovine kidney by means of chemical modification
Makarchikov, Alexander F; Luchko, A. A.; Bettendorff, Lucien ULg et al

in News of Biomedical Sciences (2002), 3

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See detailAdenylate kinase 1 knockout mice have normal thiamine triphosphate levels
Makarchikov, Alexander F; Wins, Pierre; Janssen, E. et al

in Biochimica et Biophysica Acta-Molecular Cell Research (2002), 1592(2), 117-121

Thiamine triphosphate (ThTP) is found at low concentrations in most animal tissues and it may act as a phosphate donor for the phosphorylation of proteins, suggesting a potential role in cell signaling ... [more ▼]

Thiamine triphosphate (ThTP) is found at low concentrations in most animal tissues and it may act as a phosphate donor for the phosphorylation of proteins, suggesting a potential role in cell signaling. Two mechanisms have been proposed for the enzymatic synthesis of ThTP. A thiamine diphosphate (ThDP) kinase (ThDP + ATP double left right arrow ThTP + ADP) has been purified from brewer's yeast and shown to exist in rat liver. However, other data suggest that, at least in skeletal muscle, adenylate kinase I (AK1) is responsible for ThTP synthesis. In this study, we show that AK1 knockout mice have normal ThTP levels in skeletal muscle, heart, brain, liver and kidney, demonstrating that AK1 is not responsible for ThTP synthesis in those tissues. We predict that the high ThTP content of particular tissues like the Electrophorus electricus electric organ, or pig and chicken skeletal muscle is more tightly correlated with high ThDP kinase activity or low soluble ThTPase activity than with non-stringent substrate specificity and high activity of adenylate kinase. (C) 2002 Elsevier Science B.V All rights reserved. [less ▲]

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See detailATP-driven, Na(+)-independent inward Cl- pumping in neuroblastoma cells
Bettendorff, Lucien ULg; Lakaye, Bernard ULg; Margineanu, Ilca et al

in Journal of Neurochemistry (2002), 81(4), 792-801

In immature neurones, the steady-state intracellular Cl- concentration [Cl-](i) is generally higher than expected for passive distribution, and this is believed to be due to Na(+)-K(+)-2Cl(-) co-transport ... [more ▼]

In immature neurones, the steady-state intracellular Cl- concentration [Cl-](i) is generally higher than expected for passive distribution, and this is believed to be due to Na(+)-K(+)-2Cl(-) co-transport. Here, we show that N2a neuroblastoma cells, incubated in HEPES-buffered NaCl medium maintain a [Cl-](i) around 60 mm, two- to threefold higher than expected for passive distribution at a membrane potential of - 49 mV. When the cells were transferred to a Cl(-) -free medium, [Cl-](i) decreased quickly (t(1/2) < 5 min), suggesting a high Cl- permeability. When the intracellular ATP concentration was reduced to less than 1 mm by metabolic inhibitors, the initial rate of (36) Cl- uptake was strongly inhibited (60-65%) while steady-state [Cl-](i) decreased to 24 mm, close to the value predicted from the Nernst equilibrium. Moreover, after reduction of [ATP](i) and [Cl-](i) by rotenone, the subsequent addition of glucose led to a reaccumulation of Cl-, in parallel with ATP recovery. Internal bicarbonate did not affect Cl- pumping, suggesting that Cl-/HCO(3)(-) exchange does not significantly contribute to active transport. Likewise, Na(+) -K(+) -2Cl(-) co-transport also appeared to play a minor role: although mRNA for the NKCC1 form of the co-transporter was detected in N2a cells, neither the initial rate of (36)Cl- uptake nor steady-state [Cl-](i) were appreciably decreased by 10 microm bumetanide or replacement of external Na(+) by choline. These results suggest that a highly active ATP-dependent mechanism, distinct from Na(+) -K(+) -2Cl(-) co-transport, is responsible for most of the inward Cl- pumping in N2a cells. [less ▲]

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See detailSpecific phosphorylation of Torpedo 43 rapsyn by endogenous kinase(s) with thiamine triphosphate as the phosphate donor
Nghiêm, Hoang O; Bettendorff, Lucien ULg; Changeux, Jean-Pierre

in FASEB Journal (2000), 14

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See detailThiamine triphosphate, a new modulator of protein activity
Bettendorff, Lucien ULg

Conference (1999)

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See detailThiamine derivatives in excitable tissues: Metabolism, deficiency and neurodegenerative diseases
Bettendorff, Lucien ULg; Wins, Pierre

in Pandalai, S. G. (Ed.) Recent Research Developments in Neurochemistry, vol 2, part 1 (1999)

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See detailThe molecular neuron-glia couple and epileptogenesis
Grisar, Thierry ULg; Lakaye, Bernard ULg; Thomas, Elizabeth et al

in Delgado-Escueta, A. V.; Wilson, W. A.; Olsen, R. W. (Eds.) et al Jasper's Basic Mechanisms of the Epilepsies, 3rd edition (1999)

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See detailReversibility of thiamine deficiency-induced partial necrosis and mitochondrial uncoupling by addition of thiamine to neuroblastoma cell suspensions.
Bettendorff, Lucien ULg; Goessens, Guy ULg; Sluse, Francis ULg

in Molecular and Cellular Biochemistry (1997), 174(1-2), 121-4

Culture of neuroblastoma cells in the presence of low thiamine concentration (16 nM) and of the transport inhibitor amprolium leads to the appearance of signs of necrosis: the chromatin condenses, the ... [more ▼]

Culture of neuroblastoma cells in the presence of low thiamine concentration (16 nM) and of the transport inhibitor amprolium leads to the appearance of signs of necrosis: the chromatin condenses, the oxygen consumption decreases and is uncoupled, the mitochondrial cristae are disorganized, the thiamine diphosphate-dependent dehydrogenase activities are impaired. When 10 microM thiamine are added to these cells, the basal respiration increases, the coupled respiration is restored and mitochondrial morphology is recovered within 1 h. Addition of succinate, which is oxidized via a thiamine diphosphate-independent dehydrogenase, to digitonin-permeabilized cells immediately restores a coupled respiration. Our results suggest that the slowing of the citric acid cycle is the cause of the biochemical lesion induced by severe thiamine deficiency and that part of the mitochondria remain functional. [less ▲]

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See detailLow Thiamine Diphosphate Levels in Brains of Patients with Frontal Lobe Degeneration of the Non-Alzheimer's Type
Bettendorff, Lucien ULg; Mastrogiacomo, Frank; Wins, Pierre et al

in Journal of Neurochemistry (1997), 69(5), 2005-2010

We compared the thiamine and thiamine phosphate contents in the frontal, temporal, parietal, and occipital cortex of six patients with frontal lobe degeneration of the non-Alzheimer's type (FNAD) or ... [more ▼]

We compared the thiamine and thiamine phosphate contents in the frontal, temporal, parietal, and occipital cortex of six patients with frontal lobe degeneration of the non-Alzheimer's type (FNAD) or frontotemporal dementia with five age-, postmortem delay-, and agonal status-matched control subjects. Our results reveal a 40-50% decrease in thiamine diphosphate (TDP) in the cortex of FNAD patients, whereas thiamine monophosphate was increased 49-119%. TDP synthesizing and hydrolyzing enzymes were unaffected. The activity of citrate synthase, a mitochondrial marker enzyme, was decreased in the frontal cortex of patients with FNAD, but no correlation with TDP content was found. These results suggest that decreased contents of TDP, which is essentially mitochondrial, is a specific feature of FNAD. As TDP is an essential cofactor for oxidative metabolism and neurotransmitter synthesis, and because low thiamine status (compared with other species) is a constant feature in humans, a nearly 50% decrease in cortical TDP content may contribute significantly to the clinical symptoms observed in FNAD. This study also provides a basis for a trial of thiamine, to improve the cognitive status of the patients. [less ▲]

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See detailParadoxical Sleep Deprivation Increases the Content of Glutamate and Glutamine in Rat Cerebral Cortex
Bettendorff, Lucien ULg; Sallanon-Moulin, M.; Touret, Monique et al

in Sleep (1996), 19(1), 65-71

We investigated the influence of the sleep/waking cycle, the effects of paradoxical sleep deprivation (PSD) and of the vigilance-promoting drug modafinil on the amino acid contents of rat brain cortex. No ... [more ▼]

We investigated the influence of the sleep/waking cycle, the effects of paradoxical sleep deprivation (PSD) and of the vigilance-promoting drug modafinil on the amino acid contents of rat brain cortex. No significant nycthemeral variations in amino acid levels could be detected. PSD (12-24 hours), using the water tank method, significantly increased the levels of glutamate and glutamine. The increase was still observed after the sleep rebound period. gamma-Aminobutyric acid (GABA) levels did not change significantly during the instrumental sleep deprivation but increased during the rebound period. Control experiments indicate that the increase in glutamate and glutamine levels is due to PSD rather than to the stress associated with the experimental procedure. The increase in glutamate content cannot arise only from transamination reactions, because the levels of other amino acids (such as aspartate) did not decrease. Modafinil treatment did not significantly modify the brain cortex content of any of the amino acids tested. [less ▲]

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See detailBrain Levels of Thiamine and Its Phosphate Esters in Friedreich's Ataxia and Spinocerebellar Ataxia Type 1
Bettendorff, Lucien ULg; Mastrogiacomo, Frank; LaMarche, J. et al

in Movement Disorders : Official Journal of the Movement Disorder Society (1996), 11(4), 437-439

Decreased blood and cerebrospinal fluid levels of thiamine have been reported in patients with spinocerebellar ataxia disorders. To determine whether a thiamine deficiency is present in the brain, we ... [more ▼]

Decreased blood and cerebrospinal fluid levels of thiamine have been reported in patients with spinocerebellar ataxia disorders. To determine whether a thiamine deficiency is present in the brain, we measured levels of thiamine and its phosphate esters thiamine monophosphate (TMP) and thiamine diphosphate (TDP), in postmortem cerebellar and cerebral cortices of patients with Friedreich's ataxia (FA) and spinocerebellar ataxia type 1 (SCA1). Brain levels of free (nonphosphorylated) thiamine, TMP, TDP, and total thiamine in FA and SCA1 were, on average, not significantly different from control values. However, a nonsignificant trend was observed for slightly reduced levels of TDP and total thiamine in cerebellar cortex of the SCA1 patients, a finding that might be related to the severe neuronal damage in this brain area. We conclude that in FA, brain thiamine concentrations are normal, whereas in SCA1 the levels are, at most, only slightly reduced. [less ▲]

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See detailImmunoreactive levels of α-ketoglutarate dehydrogenase subunits in Friedreich's ataxia and spinocerebellar ataxia type 1
Mastrogiacomo, Frank; LaMarche, Jacques; Dozic, Slobodan et al

in Neurodegeneration : A Journal for Neurodegenerative Disorders, Neuroprotection, and Neuroregeneration (1996), 5

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See detailA Non-Cofactor Role of Thiamine Derivatives in Excitable Cells?
Bettendorff, Lucien ULg

in Archives of Physiology & Biochemistry (1996), 104(6), 745-751

Thiamine diphosphate (TDP) is an important cofactor of pyruvate (PDH) and alpha-ketoglutarate (KGDH) dehydrogenases and transketolase. Thiamine deficiency leads to reversible and irreversible brain ... [more ▼]

Thiamine diphosphate (TDP) is an important cofactor of pyruvate (PDH) and alpha-ketoglutarate (KGDH) dehydrogenases and transketolase. Thiamine deficiency leads to reversible and irreversible brain lesions due to impaired oxidative metabolism. A specific non-cofactor role for thiamine has also been proposed in excitable cells and thiamine triphosphate (TTP) might be involved in the regulation of ion channels. Thiamine is taken up by neuroblastoma cells through a high affinity transporter. Inside the cells, it is rapidly phosphorylated to TDP. This high turnover TDP pool is the precursor for TTP. Most of the TDP however has a low turnover and is associated with PDH and KGDH in mitochondria. In excised inside-out patches from neuroblastoma cells, TTP, at a concentration of 1 microM, activates chloride channels of large unitary conductance, the so-called maxi-Cl- channels. These channels are inhibited by oxythiamine from the outide. In addition to the role of TTP in the regulation of chloride channels, thiamine itself, or a presently unknown analog, may have trophic effects on neuronal cells. [less ▲]

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See detailThiamine, Thiamine Phosphates, and Their Metabolizing Enzymes in Human Brain
Bettendorff, Lucien ULg; Mastrogiacomo, Frank; Kish, Stephen J et al

in Journal of Neurochemistry (1996), 66(1), 250-8

Total thiamine (the sum of thiamine and its phosphate esters) concentrations are two- to fourfold lower in human brain than in the brain of other mammals. There were no differences in the total thiamine ... [more ▼]

Total thiamine (the sum of thiamine and its phosphate esters) concentrations are two- to fourfold lower in human brain than in the brain of other mammals. There were no differences in the total thiamine content between biopsied and autopsied human brain, except that in the latter, thiamine triphosphate was undetectable. The main thiamine phosphate-metabolizing enzymes could be detected in autopsied brain, and the kinetic parameters were comparable to those reported in other species. Thiamine diphosphate levels were lowest in hippocampus (15 +/- 4 pmol/mg of protein) and highest in mammillary bodies (24 +/- 4 pmol/mg of protein). Maximal levels of thiamine and its phosphate ester were found to be present at birth. In parietal cortex and globus pallidus, mean levels of total thiamine in the oldest age group (77-103 years) were, respectively, 21 and 26% lower than those in the middle age group (40-55 years). Unlike cerebral cortex, the globus pallidus showed a sharp drop in thiamine diphosphate levels during infancy, with concentrations in the oldest group being only approximately 50% of the levels present during the first 4 months of life. These data, consistent with previous observations conducted in blood, suggest a tendency toward decreased thiamine status in older people. [less ▲]

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