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See detailMethyl-laudanosine: A new pharmacological tool to investigate the function of small-conductance Ca2+-activated K+ channels
Scuvée-Moreau, Jacqueline ULg; Liégeois, Jean-François ULg; Massotte, Laurent ULg et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2002), 302(3), 1176-1183

Small-conductance Ca(2+)-activated K(+) channels (SK channels) underlie the prolonged postspike afterhyperpolarization (AHP) observed in many central neurons and play an important role in modulating ... [more ▼]

Small-conductance Ca(2+)-activated K(+) channels (SK channels) underlie the prolonged postspike afterhyperpolarization (AHP) observed in many central neurons and play an important role in modulating neuronal activity. However, a lack of specific and reversible blockers of these channels hampers their study in various experimental conditions. Because previous work has shown that bicuculline salts block these channels, we examined whether related alkaloids, namely laudanosine quaternary derivatives, would produce similar effects. Intracellular recordings were performed on rat midbrain dopaminergic neurons and hippocampus CA1 pyramidal cells. Binding experiments were performed on rat cerebral cortex membranes. Laudanosine, methyl-laudanosine, and ethyl-laudanosine blocked the apamin-sensitive AHP of dopaminergic neurons with mean IC(50) values of 152, 15, and 47 microM, respectively. The benzyl and butyl derivatives were less potent. Methyl-laudanosine had no effect on the I(h) current, action potential parameters, or membrane resistance of dopaminergic cells, or on the decrease in input resistance induced by muscimol, indicating a lack of antagonism at GABA(A) receptors. Interestingly, 100 microM methyl-laudanosine induced a significant increase in spiking frequency of dopaminergic neurons but not of CA1 pyramidal cells, suggesting the possibility of regional selectivity. Binding experiments on laudanosine derivatives were in good agreement with electrophysiological data. Moreover, methyl-laudanosine has no affinity for voltage-gated potassium channels, and its affinity for SK channels (IC(50) 4 microM) is superior to its affinity for muscarinic (IC(50) 114 microM) and neuronal nicotinic (IC(50) > or =367 microM) receptors. Methyl-laudanosine may be a valuable pharmacological tool to investigate the role of SK channels in various experimental models. [less ▲]

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See detailMethylation analysis of the imprinted DLK1-GTL2 domain supports the random parental origin of the IGH-involving del(14q) in B-cell malignancies.
Katrincsakova, Beata; Takeda, Haruko ULg; Urbankova, Helena et al

in Epigenetics : Official Journal of the DNA Methylation Society (2009), 4(7), 469-75

Leukemias/lymphomas with IGH-involving del(14q)(1) commonly lose the DLK1-GTL2 imprinted domain that comprises several paternally and maternally expressed genes, including a cluster of microRNAs. Given ... [more ▼]

Leukemias/lymphomas with IGH-involving del(14q)(1) commonly lose the DLK1-GTL2 imprinted domain that comprises several paternally and maternally expressed genes, including a cluster of microRNAs. Given that deletion of this region could lead to inactivation of a monoallelically expressed tumor suppressor gene, our study aimed at determination of the parental origin of del(14q/IGH). The designed allele-specific methylation study of the DLK1/GTL2 intergenic differentially methylated region allowed us to determine the parental origin of del(14q/IGH) in 9/20 analyzed cases. In six cases del(14q/IGH) was of the paternal origin and in three cases of the maternal origin. These findings argue against the concept that a TSG/anti-oncomir located in the imprinted region is systematically inactivated by a targeted deletion of its functional allele. [less ▲]

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See detailMethylene blue: An old-timer or a compound ready for revival?
Donati, A.; Preiser, Jean-Charles ULg

in Critical Care Medicine (2006), 34(11), 2862-2863

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See detailMethylglyoxal-induced carbonyl stress: perspectives of a new anti-GBM therapy
Nokin, Marie-Julie ULg

Conference (2017, February 24)

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See detailMethylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer.
Chiavarina, Barbara ULg; Nokin, Marie-Julie ULg; Bellier, Justine ULg et al

in International Journal of Molecular Sciences (2017), 18(1),

Cancer cells generally rely on aerobic glycolysis as a major source of energy. Methylglyoxal (MG), a dicarbonyl compound that is produced as a side product during glycolysis, is highly reactive and ... [more ▼]

Cancer cells generally rely on aerobic glycolysis as a major source of energy. Methylglyoxal (MG), a dicarbonyl compound that is produced as a side product during glycolysis, is highly reactive and induces the formation of advanced glycation end-products that are implicated in several pathologies including cancer. All mammalian cells have an enzymatic defense against MG composed by glyoxalases GLO1 and GLO2 that converts MG to d-lactate. Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality. In this study, we used immunohistochemistry to examine the level of MG protein adducts, in a series of 102 CRC human tumors divided into four clinical stages. We consistently detected a high level of MG adducts and low GLO1 activity in high stage tumors compared to low stage ones suggesting a pro-tumor role for dicarbonyl stress. Accordingly, GLO1 depletion in CRC cells promoted tumor growth in vivo that was efficiently reversed using carnosine, a potent MG scavenger. Our study represents the first demonstration that MG adducts accumulation is a consistent feature of high stage CRC tumors. Our data point to MG production and detoxification levels as an important molecular link between exacerbated glycolytic activity and CRC progression. [less ▲]

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See detailMethylmercury and selenium in vitro effects on harbor seal (Phoca vitulina) lymphocytes : a multidisciplinary approach
Dupont, Aurélie ULg; Bouquegneau, Jean-Marie ULg; Das, Krishna ULg et al

Poster (2010, May 26)

Methylmercury (MeHg) bioaccumulates along the food web, leading to the highest levels in tissues of predatory species. It constitutes the predominant form present in the blood of marine mammals. The blood ... [more ▼]

Methylmercury (MeHg) bioaccumulates along the food web, leading to the highest levels in tissues of predatory species. It constitutes the predominant form present in the blood of marine mammals. The blood cells, including the immune cells, are therefore exposed to the toxic properties of that chemical. Nevertheless, selenium (Se) is an essential element absorbed concomitantly to MeHg which seems to modulate this toxicity. The goal of this study is to evaluate the immunotoxicity of MeHg on the harbor seal (Phoca vitulina) T lymphocytes, highly important in the adaptive immune response, and to investigate the modulating effect of Se on that toxicity. In parallel, the concentrations of MeHg, total mercury (T-Hg) and Se are determined in free-ranging harbour seal blood in order to follow their contamination levels. The T lymphocytes were isolated from the whole blood, exposed to various MeHg and Se concentrations and the exposure effects were estimated by functional tests including the evaluation of viability, proliferation, metabolic activity, DNA and protein synthesis, and by morphological analysis by transmission electron microscopy. The mean T-Hg concentration was 172 ± 143 µg/l of whole blood. The T lymphocytes cultures in vitro displayed a decreasing number of viable cells with increasing concentrations of MeHg, and numerous ultrastructural defects. The cells exposed to MeHg notably displayed distortion of the plasmic membrane, nucleus fragmentations, chromatin compaction, swelling mitochondrias and cytoplasmic vacuolisations. Those results highlighted various immunotoxic effects of MeHg, both at the functional and ultrastructural levels. The antagonistic role of Se on MeHg immunotoxicity is discussed. [less ▲]

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See detailMethylmercury in vitro exposure of harbor seal (Phoca vitulina) lymphocytes: a multidisciplinary approach
Dupont, Aurélie ULg; Siebert, Ursula; Rosenberger, Tanja et al

Poster (2009, June 08)

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See detailUn métier à tisser thérapeutique
Triffaux, Jean-Marc ULg; Gayetot, Delphine ULg; Izzi, Isabelle

in Revue des Hôpitaux de Jour Psychiatriques et des Thérapies Institutionnelles (2008), 10

Detailed reference viewed: 47 (2 ULg)