References of "Piette, Jacques"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailEvaluation of a new biocompatible poly(N-(morpholino ethyl methacrylate)-based copolymer for the delivery of ruthenium oligonucleotides, targeting HPV16 E6 oncogene
Reschner, Anca ULg; Shim, Yong Ho; Dubois, Philippe et al

in Journal of Biomedical Nanotechnology (2013), 9

This study investigates the use of a new biocompatible block copolymer poly(2-(dimethylamino)ethyl methacrylate-N-(morpholino)ethyl methacrylate (PDMAEMA-b-PMEMA) for the delivery of a particular ... [more ▼]

This study investigates the use of a new biocompatible block copolymer poly(2-(dimethylamino)ethyl methacrylate-N-(morpholino)ethyl methacrylate (PDMAEMA-b-PMEMA) for the delivery of a particular antisense oligonucleotide targeting E6 gene from human papilloma virus. This antisense oligonucleotide was derivatized with a polyazaaromatic RuII complex which, under visible illumination, is able to produce an irreversible crosslink with the complementary targeted sequence. The purpose of this study is to determine whether by the use of a suitable transfection agent, it is possible to increase the efficiency of the antisense oligonucleotide targeting E6 gene, named Ru-P-4. In a recent study, we showed that Oligofectamine® transfected Ru-P-4 antisense oligonucleotide failed to inhibit efficiently the growth of cervical cancer cell line SiHa, contrarily to the Ru-P-6 antisense oligonucleotide, another sequence also targeting the E6 gene. The ability of PDMAEMA-b-PMEMA to form polyplexes with optimal physicochemical characteristics was investigated first. Then the ability of the PDMAEMA-b-PMEMA/Ru-P-4 antisense oligonucleotide polyplexes to transfect two keratinocyte cell lines (SiHa and HaCat) and the capacity of polyplexes to inhibit HPV16 + cervical cancer cell growth was evaluated. PDMAEMA-b-PMEMA base polyplexes at the optimal molar ratio of polymer nitrogen atoms to DNA phosphates (N/P), were able to deliver Ru-P-4 antisense oligonucleotide and to induce a higher growth inhibition in human cervical cancer SiHa cells, compared to other formulations based on Oligofectamine®. [less ▲]

Detailed reference viewed: 106 (32 ULg)
See detailCharacterization of chemotherapy-induced cell death in glioblastoma
Coupienne, Isabelle ULg; Fettweis, Grégory ULg; Piette, Jacques ULg

Poster (2012, December 10)

Glioblastoma constitute the most frequent and deadliest type of brain tumors. Their annual incidence is estimated between 5 and 8 cases per 100,000 people in Europe and North America. They are resistant ... [more ▼]

Glioblastoma constitute the most frequent and deadliest type of brain tumors. Their annual incidence is estimated between 5 and 8 cases per 100,000 people in Europe and North America. They are resistant to all current therapies and are associated with a very high rate of recurrence. The associated prognosis is generally very poor and most patients die within a year after diagnosis. Unfortunately, despite extensive research and use of multimodality treatments combining surgical resection, chemotherapy and radiotherapy, survival hasn’t really much improved over the last 20 years. Indeed, these tumors were shown to be characterized by a high radio- and chemo-resistance. Glioblastoma cells exhibit overexpression of the anti-apoptotic Bcl-2 family proteins and downregulation of its pro-apoptotic members, high expression of the IAPs (Inhibitors of Apoptosis Proteins) and constitutive activation of the pro-survival NF-κB pathway. Currently, the most commonly used treatment offering the best prognosis to patients consists in a combination of maximal surgical tumor resection (when feasible) with subsequent radio- and/or chemotherapy. Among the most commonly used chemotherapeutic agents, the alkylating agent temozolomide and the topoisomerase I inhibitor camptothecin occupy a central position. Therefore, in this study, the impact of both temozolomide and irinotecan (a soluble derivative of camptothecin) on glioma cell survival will be investigated. Important progress was made in the comprehension of the molecular mechanisms underlying tumor development and progression however, survival benefits conferred by the use of new drugs and therapeutic strategies are counted in months rather than years. Consequently, there is an urge to rapidly improve the efficiency of the currently used treatments. This research project consists in (i) the study of the mechanisms implicated in glioblastoma cell death induced by two chemotherapeutic agents : temozolomide and irinotecan, (ii) the identification of the mechanisms underlying the resistance of glioblastoma to these treatments, (iii) the use of pharmacological tools to interfere with those resistance strategies to enhance chemotherapy efficiency. Necrosis was, until recently, long thought to be only accidental. However, it was shown to be finely regulated by specific signalling pathways. Programmed necrosis often takes place in cells in which apoptosis cannot be properly activated and serves as a back-up cell death pathway. Previous work from our lab having already demonstrated that glioblastoma are, at least partially, apoptosis-defective, special emphasis is put on the study of necrotic parameters. Results from survival tests performed on several glioblastoma cell lines in the presence of necrotic inhibitors like necrostatin-1 (an inhibitor of the central regulator of the necrotic pathway RIP1) allows to partially overcome temozolomide and irinotecan-induced glioblastoma cell death, highlighting the role played by programmed necrosis in chemotherapy sensitivity. [less ▲]

Detailed reference viewed: 44 (8 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation of p65(RelA) on Ser547 by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.
Sabatel, Hélène ULg; Di Valentin, Emmanuel ULg; Gloire, Geoffrey ULg et al

in PLoS ONE (2012)

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA ... [more ▼]

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA double-strand breaks activate NF-κB in an ATM-dependent manner. In this manuscript, a direct interaction between p65(RelA) and the N-terminal extremity of ATM is reported. We also report that only one of the five potential ATM-(S/T)Q target sites present in p65, namely Ser547, is specifically phosphorylated by ATM in vitro. A comparative transcriptomic analysis performed in HEK-293 cells expressing either wild-type HA-p65 or a non-phosphorylatable mutant HA-p65S547A identified several differentially transcribed genes after an etoposide treatment (e.g. IL8, A20, SELE). The transcription of these genes is increased in cells expressing the mutant. Substitution of Ser547 to alanine does not affect p65 binding abilities on the κB site of the IL8 promoter but reduces p65 interaction with HDAC1. Cells expressing p65S547A have a higher level of histone H3 acetylated on Lys9 at the IL8 promoter, which is in agreement with the higher gene induction observed. These results indicate that ATM regulates a sub-set of NF-κB dependent genes after a genotoxic stress by direct phosphorylation of p65. [less ▲]

Detailed reference viewed: 49 (18 ULg)
Full Text
Peer Reviewed
See detailThe inositol phosphatase SHIP-1 inhibits NOD2-induced NF-κB activation by disturbing the interaction of XIAP with RIP2
Condé, Claude ULg; Rambout, Xavier ULg; Lebrun, Marielle ULg et al

in PLoS ONE (2012)

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a ... [more ▼]

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-κB activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-κB activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-κB signaling. [less ▲]

Detailed reference viewed: 43 (16 ULg)
Full Text
Peer Reviewed
See detailThe c-jun N-terminal Kinase (JNK)-binding Protein (JNKBP1) Acts as a Negative Regulator of NOD2 Protein Signaling by Inhibiting Its Oligomerization Process
Lecat, Aurore ULg; Di Valentin, Emmanuel ULg; Somja, Joan ULg et al

in Journal of Biological Chemistry (2012), 287(35), 29213-26

NOD2 is one of the best characterized member of the cytosolic NOD-like receptors (NLR) family. NOD2 is able to sense muramyl dipeptide (MDP), a specific bacterial cell wall component, and to subsequently ... [more ▼]

NOD2 is one of the best characterized member of the cytosolic NOD-like receptors (NLR) family. NOD2 is able to sense muramyl dipeptide (MDP), a specific bacterial cell wall component, and to subsequently induce various signalling pathways leading to NF- kappaB activation and autophagy, both events contributing to an efficient innate and adaptative immune response. Interestingly, loss-of-function nod2 variants were associated with a higher susceptibility for Crohn ' s disease (CD), which highlights the physiological importance of proper regulation of NOD2 activity. We performed a biochemical screen to search for new NOD2 regulators. We identified a new NOD2 partner, c-jun N-terminal kinase binding protein 1 (JNKBP1), a scaffold protein characterized by a N-terminal WD-40 domain. JNKBP1, through its WD-40 domain, binds to NOD2 following MDP activation. This interaction attenuates NOD2-mediated NF-kappaB activation and IL-8 secretion as well as NOD2 antibacterial activity. JNKBP1 exerts its repressor effect by disturbing NOD2 oligomerization and RIP2 tyrosine phosphorylation, both steps required for downstream NOD2 signalling. We furthermore showed that JNKBP1 and NOD2 are co-expressed in the human intestinal epithelium and immune cells recruited in the lamina propria, which suggests that JNKBP1 contributes to maintain NOD2-mediated intestinal immune homeostasis. [less ▲]

Detailed reference viewed: 75 (42 ULg)
Full Text
Peer Reviewed
See detailPERK IS REQUIRED AT THE ER-TO-MITOCHONDRIA CONTACT SITES TO CONVEY APOPTOSIS FOLLOWING ROS-MEDIATED ER STRESS
VERFAILLIE, T; RUBIO, N; GARG, A et al

in Cell Death & Differentiation (2012), 19

Detailed reference viewed: 37 (10 ULg)
Full Text
Peer Reviewed
See detailSpatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species.
Rubio, Noemi; Coupienne, Isabelle ULg; Di Valentin, Emmanuel ULg et al

in Autophagy (2012), 8(9), 1312-24

Although reactive oxygen species (ROS) have been reported to evoke different autophagic pathways, how ROS or their secondary products modulate the selective clearance of oxidatively damaged organelles is ... [more ▼]

Although reactive oxygen species (ROS) have been reported to evoke different autophagic pathways, how ROS or their secondary products modulate the selective clearance of oxidatively damaged organelles is less explored. To investigate the signaling role of ROS and the impact of their compartmentalization in autophagy pathways, we used murine fibrosarcoma L929 cells overexpressing different antioxidant enzymes targeted to the cytosol or mitochondria and subjected them to photodynamic (PD) stress with the endoplasmic reticulum (ER)-associated photosensitizer hypericin. We show that following apical ROS-mediated damage to the ER, predominantly cells overexpressing mitochondria-associated glutathione peroxidase 4 (GPX4) and manganese superoxide dismutase (SOD2) displayed attenuated kinetics of autophagosome formation and overall cell death, as detected by computerized time-lapse microscopy. Consistent with a primary ER photodamage, kinetics and colocalization studies revealed that photogenerated ROS induced an initial reticulophagy, followed by morphological changes in the mitochondrial network that preceded clearance of mitochondria by mitophagy. Overexpression of cytosolic and mitochondria-associated GPX4 retained the tubular mitochondrial network in response to PD stress and concomitantly blocked the progression toward mitophagy. Preventing the formation of phospholipid hydroperoxides and H 2O 2 in the cytosol as well as in the mitochondria significantly reduced cardiolipin peroxidation and apoptosis. All together, these results show that in response to apical ER photodamage ROS propagate to mitochondria, which in turn amplify ROS production, thereby contributing to two antagonizing processes, mitophagy and apoptosis. [less ▲]

Detailed reference viewed: 24 (5 ULg)
Full Text
Peer Reviewed
See detailAssessment of new biocompatible Poly(N-(morpholino)ethyl methacrylate)-based copolymers by transfection of immortalized keratinoc
Van Overstraeten-Schlögel, Nancy; Shim, Yong Ho; Tevel, Virginie et al

in Drug Delivery (2012), 16(2), 102-111

Detailed reference viewed: 27 (12 ULg)
Full Text
Peer Reviewed
See detailInduction of the Alternative NF-{kappa}B Pathway by Lymphotoxin {alpha}{beta} (LT{alpha}{beta}) Relies on Internalization of LT{beta} Receptor
Ganeff, Corine; Remouchamps, Caroline ULg; Boutaffala, Layla et al

in Molecular & Cellular Biology (2011), 21

Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still ... [more ▼]

Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still poorly understood. Using lymphotoxin β receptor (LTβR) as a prototype, we showed that activation of the alternative, but not the classical, NF-κB pathway relied on internalization of the receptor. Further molecular analyses revealed a specific cytosolic region of LTβR essential for its internalization, TRAF3 recruitment, and p100 processing. Interestingly, we found that dynamin-dependent, but clathrin-independent, internalization of LTβR appeared to be required for the activation of the alternative, but not the classical, NF-κB pathway. In vivo, ligand-induced internalization of LTβR in mesenteric lymph node stromal cells correlated with induction of alternative NF-κB target genes. Thus, our data shed light on LTβR cellular trafficking as a process required for specific biological functions of NF-κB. [less ▲]

Detailed reference viewed: 70 (16 ULg)
Full Text
Peer Reviewed
See detailImportance of the PIKKs in NF-kappaB activation by genotoxic stress
Sabatel, Hélène ULg; Pirlot, Céline ULg; Piette, Jacques ULg et al

in Biochemical Pharmacology (2011), 82(10), 1371-83

Detailed reference viewed: 30 (7 ULg)
Full Text
Peer Reviewed
See detailRIP3 Expression Induces a Death Profile Change in U2OS Osteosarcoma Cells After 5-ALA-PDT
Coupienne, Isabelle ULg; Fettweis, Grégory ULg; Piette, Jacques ULg

in Lasers in Surgery and Medicine (2011), 43(7), 557564

Background and Objective The receptor-interacting protein 3 (RIP3) has recently been outlined as a key necrosis mediator but is also thought to participate in the regulation of apoptosis. The aim of this ... [more ▼]

Background and Objective The receptor-interacting protein 3 (RIP3) has recently been outlined as a key necrosis mediator but is also thought to participate in the regulation of apoptosis. The aim of this study is to compare the cell death profile induced by 5-aminolevulic acid (5-ALA)-mediated photodynamic therapy (PDT) in the RIP3-deficient cell line U2OS and in U2OS cells in which the expression of RIP3 was restored. Materials and Methods RIP3-expressing U2OS cells (RIP3-U2OS) were obtained after transfection and antibiotic selection. Wild type and RIP3-U2OS cells were treated by 5-ALA-PDT. Overall cell viability was evaluated and different parameters characteristic of apoptosis, autophagy, and necrosis were studied. Results Surprisingly, the survival of RIP3-U2OS cells was higher compared to that of the wild type cells. In addition, RIP3-U2OS cell death was decreased by a zVAD-fmk pre-treatment. A higher cleavage of caspase-3, 7, 8, 9, and PARP was also detected in these cells, pointing out to the activation of caspase-dependent apoptosis. In parallel, a thrust of autophagy was clearly identified in the RIP3-U2OS cells. Conversely, RIP3-U2OS exhibited a lower level of necrosis than the wild types. Interestingly, necrostatin-1 efficiently decreased necrosis level in RIP3-U2OS but not in wild type cells. Conclusion Expression of RIP3 in U2OS cells led to a better survival but also to a death profile change in response to PDT. The apoptotic and autophagic pathways were clearly up-regulated compared to the RIP3-deficient wild type cells. However, induction of necrosis was weaker in the RIP3-U2OS cells. In this context, autophagy is likely to play a protective role against PDT-induced cell death and to allow a better survival of RIP3-U2OS cells. This work also highlights the important role played by RIP3 in the apoptotic pathway, although the modalities are still widely unknown. [less ▲]

Detailed reference viewed: 47 (17 ULg)
Full Text
Peer Reviewed
See detailNF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy.
Coupienne, Isabelle ULg; Bontems, Sébastien ULg; Dewaele, M. et al

in Biochemical Pharmacology (2011)

Glioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases ... [more ▼]

Glioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases, this type of tumor is characterized by a constitutive activation of the nuclear factor-kappaB (NF-kappaB). This factor is known to be a key regulator of various physiological processes such as inflammation, immune response, cell growth or apoptosis. In the present study, we explored the role of NF-kappaB activation in the sensitivity of human glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT). 5-ALA is a physiological compound widely used in PDT as well as in tumor photodetection (PDD). Our results show that inhibition of NF-kappaB improves glioblastoma cell death in response to 5-ALA-PDT. We then studied the molecular mechanisms underlying the cell death induced by PDT combined or not with NF-kappaB inhibition. We found that apoptosis was induced by PDT but in an incomplete manner and that, unexpectedly, NF-kappaB inhibition reduced its level. Oppositely PDT mainly induces necrosis in glioblastoma cells and NF-kappaB is found to have anti-necrotic functions in this context. The autophagic flux was also enhanced as a result of 5-ALA-PDT and we demonstrate that stimulation of autophagy acts as a pro-survival mechanism confering protection against PDT-mediated necrosis. These data point out that 5-ALA-PDT has an interesting potential as a mean to treat glioblastoma and that inhibition of NF-kappaB renders glioblastoma cells more sensitive to the treatment. [less ▲]

Detailed reference viewed: 31 (5 ULg)
Full Text
Peer Reviewed
See detailThe varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3.
Vandevenne, Patricia ULg; Lebrun, Marielle ULg; El Mjiyad, Nadia et al

in PLoS ONE (2011), 9(2),

The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by ... [more ▼]

The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by specific host pathogen recognition receptors triggering the activation of IRF3. IRF3, along with NF-kappaB, is a key regulator of IFN-beta expression. Until now, the role of IRF3 in the activation of the innate immune response during Varicella-Zoster Virus (VZV) infection has been poorly studied. In this work, we demonstrated for the first time that VZV rapidly induces an atypical phosphorylation of IRF3 that is inhibitory since it prevents subsequent IRF3 homodimerization and induction of target genes. Using a mutant virus unable to express the viral kinase ORF47p, we demonstrated that (i) IRF3 slower-migrating form disappears; (ii) IRF3 is phosphorylated on serine 396 again and recovers the ability to form homodimers; (iii) amounts of IRF3 target genes such as IFN-beta and ISG15 mRNA are greater than in cells infected with the wild-type virus; and (iv) IRF3 physically interacts with ORF47p. These data led us to hypothesize that the viral kinase ORF47p is involved in the atypical phosphorylation of IRF3 during VZV infection, which prevents its homodimerization and subsequent induction of target genes such as IFN-beta and ISG15. [less ▲]

Detailed reference viewed: 39 (7 ULg)
See detailidentification of new parterns of the NOD2 protein
Lecat, Aurore ULg; Di Valentin, Emmanuel ULg; Fillet, Marianne ULg et al

Poster (2011, January 27)

Detailed reference viewed: 25 (12 ULg)
See detailRole of MDC1 in NF-kappaB activation by DNA double-strand breaks.
Sabatel, Hélène; Piette, Jacques ULg; Habraken, Yvette ULg

Poster (2011, January 25)

Detailed reference viewed: 7 (0 ULg)
See detailStudy of the combined effect of 5-ALA-based photodynamic therapy and NF-kappaB inhibition on human glioblastoma cell survival
Coupienne, Isabelle ULg; Fettweis, Grégory ULg; Piette, Jacques ULg

Poster (2011, January)

Glioblastoma constitute the most frequent and deadliest type of brain tumors in human adults. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most ... [more ▼]

Glioblastoma constitute the most frequent and deadliest type of brain tumors in human adults. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases, this type of tumor is characterized by a constitutive activation of the nuclear factor-kappaB (NF-kappaB). This factor is known to be a key regulator of various physiological processes such as inflammation, immune response, cell growth or apoptosis. In the present study, we explored the role of NF-kappaB activation in the sensitivity of human glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)–based photodynamic therapy (PDT). Our results show that inhibition of NF-kappaB improves glioblastoma cell death in response to 5-ALA-PDT. We then studied the molecular mechanisms underlying the cell death induced by PDT combined or not with NF-kappaB inhibition. We found that PDT mainly induced necrosis in glioblastoma cells and NF-kappaB was found to have anti-necrotic functions in this context. In the second part of this study, we examined the role of the kinase RIP3, recently identified as a key effector of the necrotic pathway, in 5-ALA-PDT-induced necrosis and studied whether NF-kappaB interfered in RIP3-dependent necrosis induction. [less ▲]

Detailed reference viewed: 13 (0 ULg)