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See detailDifferential usage of NF-kB activating signals by IL-1b and TNF-a in pancreatic beta cells
Ortis, Fernanda; Miani, M; Colli, ML et al

in FEBS Letters (2012), 586

The cytokines interleukin (IL)-1b and tumor necrosis factor (TNF)-a induce b-cell death in type 1 diabetes via NF-kB activation. IL-1b induces a more marked NF-kB activation than TNF-a, with higher ... [more ▼]

The cytokines interleukin (IL)-1b and tumor necrosis factor (TNF)-a induce b-cell death in type 1 diabetes via NF-kB activation. IL-1b induces a more marked NF-kB activation than TNF-a, with higher expression of genes involved in b-cell dysfunction and death. We show here a differential usage of the IKK complex by IL-1b and TNF-a in b-cells. While TNF-a uses IKK complexes containing both IKKa and IKKb, IL-1b induces complexes with IKKa only; this effect is achieved by induction of IKKb degradation via the proteasome. Both IKKg and activation of the TRAF6-TAK1-JNK pathway are involved in IL-1b-induced IKKb degradation. [less ▲]

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See detailA peptide mimicking the C-terminal part of the reactive center loop induces the transition to the latent form of Plasminogen Activator Inhibitor Type-1
D'Amico, Salvino ULg; Martial, Joseph ULg; Struman, Ingrid ULg

in FEBS Letters (2012), 586

Plasminogen Activator Inhibitor-1 (PAI-1) is the primary inhibitor of plasminogen activators (uPA and tPA) and thus plays a central role in fibrinolysis. The spontaneous insertion of its Reactive Centre ... [more ▼]

Plasminogen Activator Inhibitor-1 (PAI-1) is the primary inhibitor of plasminogen activators (uPA and tPA) and thus plays a central role in fibrinolysis. The spontaneous insertion of its Reactive Centre Loop (RCL) into beta-sheet A is responsible for its irreversible conversion into the inactive latent form. In this study, we used two peptides mimicking residues P14-P9 and P8-P3 of the RCL so as to understand this dynamic process. We show that both peptides inhibit the formation of PAI 1/uPA and PAI-1/tPA complexes via two different mechanisms. Targeting the N-terminal part of the loop induces the cleavage of PAI-1 by the proteases uPA/tPA while targeting its C-terminal part greatly favors the irreversible formation of latent PAI-1. [less ▲]

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See detailCharacterization of a novel aphid prenyltransferase displaying dual geranyl/farnesyl diphosphate synthase activity
Vandermoten, Sophie ULg; Charloteaux, Benoît ULg; Santini, S. et al

in FEBS Letters (2008), 582(16), 19281934

We report on the cDNA cloning and characterization of a novel short-chain isoprenyl diphosphate synthase from the aphid Myzus persicae. Of the three IPPS cDNAs we cloned, two yielded prenyltransferase ... [more ▼]

We report on the cDNA cloning and characterization of a novel short-chain isoprenyl diphosphate synthase from the aphid Myzus persicae. Of the three IPPS cDNAs we cloned, two yielded prenyltransferase activity following expression in Escherichia coli; these cDNAs encode identical proteins except for the presence, in one of them, of an N-terminal mitochondrial targeting peptide. Although the aphid enzyme was predicted to be a farnesyl diphosphate synthase by BLASTP analysis, rMpIPPS, when isopentenyl diphosphate and dimethylallyl diphosphate are supplied as substrates, typically generated geranyl diphosphate (C10) as its main product, along with significant quantities of farnesyl diphosphate (C15). Analysis of an MpIPPS homology model pointed to substitutions that could confer GPP/FPP synthase activity to the aphid enzyme. [less ▲]

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See detailFunctional and profiling studies prove that prostate cancer upregulated neuroblastoma thymosin beta is the true human homologue of rat thymosin beta 15
Dhaese, S.; Jonckheere, V.; Goethals, M. et al

in FEBS Letters (2007), 581(25), 4809-4815

A peptide with a sequence identical to rat thymosin beta(Tb)15 was reported to be upregulated in human prostate cancer. However, in this report we provide evidence that TbNB, initially identified in human ... [more ▼]

A peptide with a sequence identical to rat thymosin beta(Tb)15 was reported to be upregulated in human prostate cancer. However, in this report we provide evidence that TbNB, initially identified in human neuroblastoma, is the only Tb isoform upregulated in human prostate cancer and that the Tb15 sequence is not present herein. In addition, we demonstrate that human TbNB has a higher affinity for actin in comparison to Tb4 and promotes cell migration. In combination, this experimentally validates TbNB as functional homologue of rat Tb15 in the human organism and clarifies the current composition of the human Tb family. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. [less ▲]

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See detailTransition metal transport
Krämer, Ute; Talke, Ina N.; Hanikenne, Marc ULg

in FEBS Letters (2007), 581(12 Sp. Iss. SI), 2263-2272

Transition metal transporters are of central importance in the plant metal homeostasis network which maintains internal metal concentrations within physiological limits. An overview is given of the ... [more ▼]

Transition metal transporters are of central importance in the plant metal homeostasis network which maintains internal metal concentrations within physiological limits. An overview is given of the functions of known transition metal transporters in the context of the unique chemical properties of their substrates. The modifications of the metal homeostasis network associated with the adaptation to an extreme metalliferous environment are illustrated in two Brassicaceae metal hyperaccumulator model plants based on cross-species transcriptomics studies. In a comparison between higher plants and unicellular algae, hypotheses are generated for evolutionary changes in metal transporter complements associated with the transition to multicellularity. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. [less ▲]

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See detailRegulation of uncoupling protein activity in phosphorylating potato tuber mitochondria.
Navet, R.; Douette, P.; Puttique-Marique, F. et al

in FEBS Letters (2005), 579

In isolated potato tuber mitochondria, palmitic acid (PA) can induce a H+ leak inhibited by GTP in the phosphorylating (state 3) respiration but not in the resting (state 4) respiration. The PA-induced H ... [more ▼]

In isolated potato tuber mitochondria, palmitic acid (PA) can induce a H+ leak inhibited by GTP in the phosphorylating (state 3) respiration but not in the resting (state 4) respiration. The PA-induced H+ leak is constant when state 3 respiration is decreased by an inhibition of the succinate uptake with n-butyl malonate (nBM). We show that the efficiency of inhibition by GTP is decreased when state 3 respiration is progressively inhibited by antimycin A (AA) and is restored following subsequent addition of nBM. We propose that in phosphorylating potato tuber mitochondria, the redox state of ubiquinone, which can antagonistically be varied with AA and nBM, modulates inhibition of the PA-activated UCP-sustained H+ leak by GTP. [less ▲]

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See detailThe effect of growth at low temperature on the activity and expression of the uncoupling protein in Acanthamoeba castellanii mitochondria.
Jarmuszkiewicz, W.; Antos, N.; swida, A. et al

in FEBS Letters (2004), 569

Mitochondria of amoeba Acanthamoeba castellanii, a non-photosynthetic soil amoeboid protozoon, possess an uncoupling protein (AcUCP) that mediates free fatty acid-activated proton re-uptake dissipating ... [more ▼]

Mitochondria of amoeba Acanthamoeba castellanii, a non-photosynthetic soil amoeboid protozoon, possess an uncoupling protein (AcUCP) that mediates free fatty acid-activated proton re-uptake dissipating the proton electrochemical gradient built up by respiration. The present study provides the first evidence that UCP could be a cold response protein in unicellulars. In mitochondria isolated from an amoeba batch culture grown temporarily at low temperature (6 degrees C), the content of AcUCP was increased and correlated with an increase in the linoleic acid (LA)-stimulated UCP-mediated carboxyatractyloside-resistant state 4 respiration, as compared to a control culture (routinely grown at 28 degrees C). Moreover, the cytochrome pathway activity was found to be insensitive to the cold exposure of amoeba cells, as indicated by respiration and membrane potential measurements as well as by an absence of change in the adenine nucleotide translocator and cytochrome oxidase expression levels. Furthermore, in mitochondria from the low-temperature-grown cells, at fixed LA concentration, the increased contribution of AcUCP activity to total mitochondrial phosphorylating respiration accompanied by lower coupling parameters was found, as was confirmed by calculation of this contribution using ADP/O measurements. [less ▲]

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See detailPotato Tuber Phospholipids Contain Colneleic Acid In The 2-Position
Fauconnier, Marie-Laure ULg; Williams, Td.; Marlier, M. et al

in FEBS Letters (2003), 538(1-3),

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See detailTranscription-coupled TA and GC strand asymmetries in the human genome
Touchon, M.; Nicolay, Samuel ULg; Arneodo, Alain et al

in FEBS Letters (2003), 555

Abstract Analysis of the whole set of human genes reveals that most of them present TA and GC skews, that these biases are correlated to each other and are speci¢c to gene sequences, exhibiting sharp ... [more ▼]

Abstract Analysis of the whole set of human genes reveals that most of them present TA and GC skews, that these biases are correlated to each other and are speci¢c to gene sequences, exhibiting sharp transitions between transcribed and non-tran- scribed regions. The GC asymmetries cannot be explained solely by a model previously proposed for (G+T) skew based on tran- sitions measured in a small set of human genes. We propose that the GC skew results from additional transcription-coupled mu- tation process that would include transversions. During evolu- tion, both processes acting on a large majority of genes in germ- line cells would have produced these transcription-coupled strand asymmetries. [less ▲]

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See detailHuman immune cells express ppMCH mRNA and functional MCHR1 receptor
Verlaet, Myriam ULg; Adamantidis, Antoine ULg; Coumans, Bernard ULg et al

in FEBS Letters (2002), 527(1-3), 205-210

Melanin-concentrating hormone (MCH) is highly expressed in the brain and modulates feeding behavior. It is also expressed in some peripheral tissues where its role remains unknown. We have investigated ... [more ▼]

Melanin-concentrating hormone (MCH) is highly expressed in the brain and modulates feeding behavior. It is also expressed in some peripheral tissues where its role remains unknown. We have investigated MCH function in human and mouse immune cells. RT-PCR analysis revealed a low expression of prepro-MCH and MCH receptor 1 (MCHR1) but not of MCHR2 transcript in tissular and peripheral blood immune cells. FACS and in vitro assay studies demonstrated that MCHR1 receptor expression on most cell types can trigger, in the presence of MCH, cAMP synthesis and calcium mobilization in peripheral blood mononuclear cells (PBMCs). Moreover, MCH treatment decreases the CD3-stimulated PBMC proliferation in vitro. Accordingly, our data indicate for the first time that MCH and MCHR1 may exert immunomodulatory functions. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. [less ▲]

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See detailThe intracellular tyrosine residues of the ATP-gated P2X(1) ion channel are essential for its function.
Oury, Cécile ULg; Toth-Zsamboki, Emese; Watanabe, Hiroyuki et al

in FEBS Letters (2002)

In this study, we mutated the four highly conserved intracellular tyrosine residues of the P2X(1) ion channel were mutated into phenylalanine. Simultaneous electrophysiological and calcium measurements in ... [more ▼]

In this study, we mutated the four highly conserved intracellular tyrosine residues of the P2X(1) ion channel were mutated into phenylalanine. Simultaneous electrophysiological and calcium measurements in transfected human embryonic kidney (HEK 293) cells indicated that Y362F and Y370F mutants were non-functional, despite their proper plasma membrane expression. The Y16F and Y363F mutants retained 2.2% and 26% of the wild-type P2X(1) activity, respectively. However, no tyrosine phosphorylation was detected on Western blots of P2X(1) immunoprecipitates derived either from HEK 293 cell lysates or from human platelets, expressing P2X(1) endogenously. Thus, Y16, Y362, Y363 and Y370 are required for the appropriate three-dimensional structure and function of the intracellular P2X(1) domains. [less ▲]

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See detailUncoupling proteins outside the animal and plant kingdoms: functional and evolutionary aspects.
Sluse, Francis ULg; Jarmuszkiewicz, W.

in FEBS Letters (2002), 510

The appearance of intracellular oxidative phosphorylation at the time of acquisition of mitochondria in Eukarya was very soon accompanied by the emergence of uncoupling protein, a carrier specialized in ... [more ▼]

The appearance of intracellular oxidative phosphorylation at the time of acquisition of mitochondria in Eukarya was very soon accompanied by the emergence of uncoupling protein, a carrier specialized in free fatty acid-mediated H(+) recycling that can modulate the tightness of coupling between mitochondrial respiration and ATP synthesis, thereby maintaining a balance between energy supply and demand in the cell and defending cells against damaging reactive oxygen species production when electron carriers of the respiratory chain become over-reduced. The simultaneous occurrence of redox free energy-dissipating oxidase, which has the same final effect, could be related to the functional interactions between both dissipative systems [less ▲]

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See detailUncoupling protein and alternative oxidase of Dictyostelium discoideum: occurrence, properties and protein expression during vegetative life and starvation-induced early development.
Jarmusszkiewicz, W.; Behrendt, M.; Navet, R. et al

in FEBS Letters (2002), 532

In this study we show that mitochondria of Dictyostelium discoideum contain both alternative oxidase (AOX) and uncoupling protein (UCP). AOX was stimulated by purine mononucleoside and was monomeric. UCP ... [more ▼]

In this study we show that mitochondria of Dictyostelium discoideum contain both alternative oxidase (AOX) and uncoupling protein (UCP). AOX was stimulated by purine mononucleoside and was monomeric. UCP was stimulated by free fatty acids and was poorly sensitive to GTP. Both proteins collaborated in energy dissipation when activated together. AOX expression in free-living ameboid cells decreased strongly from exponential to stationary phase of growth but much less during starvation-induced aggregation. In contrast, UCP expression was constant in all conditions indicating permanent need. Our results suggest that AOX could play a role in cell differentiation, mainly by protecting prespore cells from programmed cell death. [less ▲]

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See detailRespiratory chain network in mitochondria of Candida parapsilosis: ADP/O appraisal of the multiple electron pathways.
Milani, G.; Jarmuszkiewicz, W.; Sluse-Goffart, C. et al

in FEBS Letters (2001), 508

In this study we demonstrated that mitochondria of Candida parapsilosis contain a constitutive ubiquinol alternative oxidase (AOX) in addition to a classical respiratory chain (CRC) and a parallel ... [more ▼]

In this study we demonstrated that mitochondria of Candida parapsilosis contain a constitutive ubiquinol alternative oxidase (AOX) in addition to a classical respiratory chain (CRC) and a parallel respiratory chain (PAR) both terminating by two different cytochrome c oxidases. The C. parapsilosis AOX is characterized by a fungi-type regulation by GMP (as a stimulator) and linoleic acid (as an inhibitor). Inhibitor screening of the respiratory network by the ADP/O ratio and state 3 respiration determinations showed that (i) oxygen can be reduced by the three terminal oxidases through four paths implying one bypass between CRC and PAR and (ii) the sum of CRC, AOX and PAR capacities is higher than the overall respiration (no additivity) and that their engagement could be progressive according to the redox state of ubiquinone, i.e. first cytochrome pathway, then AOX and finally PAR. [less ▲]

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See detailCloning and expression analysis of an inducible HSP70 gene from tilapia fish
Molina, Alfredo; Biemar, Frédéric; Muller, Ferenc et al

in FEBS Letters (2000), 474(1), 5-10

We isolated and characterized the tilapia (Oreochromis mossambicus) HSP70 gene, highly homologous to other HSP70 genes. A dramatic increase of tilapia HSP70 mRNA levels was observed after heat shock of ... [more ▼]

We isolated and characterized the tilapia (Oreochromis mossambicus) HSP70 gene, highly homologous to other HSP70 genes. A dramatic increase of tilapia HSP70 mRNA levels was observed after heat shock of whole animals in all organs tested. Reporter constructs were tested for transient expression in carp cells and in microinjected zebrafish embryos. The entire isolated regulatory region (-851/+157) was able to mediate heat shock inducible expression of the reporter gene, with no preference for a particular tissue. Our studies represent the first transcriptional analysis of a HSP70 promoter from fish, revealing a powerful tool to direct controlled, tissue-independent gene expression in fish. [less ▲]

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See detailERK activation upon hypoxia: involvement in HIF-1 activation.
Minet, E.; Arnould, T.; Michel, G. et al

in FEBS Letters (2000), 468(1), 53-8

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor activated by hypoxia. The HIF-1 activation transduction pathway is poorly understood. In this report, we investigated the activation of ... [more ▼]

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor activated by hypoxia. The HIF-1 activation transduction pathway is poorly understood. In this report, we investigated the activation of extracellular regulated kinases (ERK) in hypoxia and their involvement in HIF-1 activation. We demonstrated that in human microvascular endothelial cells-1 (HMEC-1), ERK kinases are activated during hypoxia. Using dominant negative mutants, we showed that ERK1 is needed for hypoxia-induced HIF-1 transactivation activity. Moreover, using a kinase assay and Western blot experiments, we showed that HIF-1alpha is phosphorylated in hypoxia by an ERK-dependent pathway. These results evidence the role of mitogen-activated protein kinase in the transcriptional response to hypoxia. [less ▲]

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See detailIdentification and characterization of a protozoan uncoupling protein in Acanthamoeba castellanii.
Jarmuszkiwicz, W.; Milani, G.; Fortes, F. et al

in FEBS Letters (2000), 467

An uncoupling protein (UCP) was identified in mitochondria from Candida parapsilosis (CpUCP), a non-fermentative parasitic yeast. CpUCP was immunodetected using polyclonal antibodies raised against plant ... [more ▼]

An uncoupling protein (UCP) was identified in mitochondria from Candida parapsilosis (CpUCP), a non-fermentative parasitic yeast. CpUCP was immunodetected using polyclonal antibodies raised against plant UCP. Activity of CpUCP, investigated in mitochondria depleted of free fatty acids, was stimulated by linoleic acid (LA) and inhibited by GTP. Activity of CpUCP enhanced state 4 respiration by decreasing DeltaPsi and lowered the ADP/O ratio. Thus, it was able to divert energy from oxidative phosphorylation. The voltage dependence of electron flux indicated that LA had a pure protonophoretic effect. The discovery of CpUCP proves that UCP-like proteins occur in the four eukaryotic kingdoms: animals, plants, fungi and protists. [less ▲]

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See detailInteraction between Class B Beta-Lactamases and Suicide Substrates of Active-Site Serine Beta-Lactamases
Prosperi-Meys, C.; Llabres, Gabriel ULg; De Seny, Dominique ULg et al

in FEBS Letters (1999), 443(2), 109-11

The most widely used inactivators of active-site serine beta-lactamases behave as substrates of four class B metallo-beta-lactamases, but the efficiency of the catalytic process can vary by several orders ... [more ▼]

The most widely used inactivators of active-site serine beta-lactamases behave as substrates of four class B metallo-beta-lactamases, but the efficiency of the catalytic process can vary by several orders of magnitude. A comparison of the kinetic parameters for the alpha and beta isomers of 6-iodopenicillanic acid shows that there is no general preference for the alpha isomer and that the efficient hydrolysis of imipenem by these enzymes must rest on other factors. [less ▲]

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See detailHistidine modification and mutagenesis point to the involvement of a large conformational change in the mechanism of action of phage lambda lysozyme
Evrard, Christine ULg; Fastrez, Jacques; Soumillion, Patrice

in FEBS Letters (1999), 460

Phage lambda lysozyme is structurally related to other known lysozymes but its mechanism of action is different from the classical lysozyme mechanism, acting as a transglycosidase rather than a hydrolase ... [more ▼]

Phage lambda lysozyme is structurally related to other known lysozymes but its mechanism of action is different from the classical lysozyme mechanism, acting as a transglycosidase rather than a hydrolase. As two conformations have been revealed by the crystal structure, we investigated the effect of mutating and modifying a histidine located near to or far from the active site in the respective closed and open conformations. Whereas its asparagine mutation has little or no effect on activity, its N-carbethoxylation inactivates the enzyme. This provide further evidence for the involvement of the closed conformation and for the need of conformational mobility in lambda lysozyme function. [less ▲]

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