References of "Mouithys-Mickalad, Ange"
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See detailEquiNox2: a new method to measure NADPH oxidase activity and to study effect of inhibitors and their interactions with the enzyme
Derochette, Sandrine ULg; Serteyn, Didier ULg; Mouithys-Mickalad, Ange ULg et al

in Talanta (in press)

Excessive neutrophil stimulation and reactive oxygen species (ROS) production are involved in numerous human or horse pathologies. The modulation of the neutrophil NADPH oxidase (NOX) has a great ... [more ▼]

Excessive neutrophil stimulation and reactive oxygen species (ROS) production are involved in numerous human or horse pathologies. The modulation of the neutrophil NADPH oxidase (NOX) has a great therapeutic potential since this enzyme produces superoxide anion whose most of the other ROS derive. The measurement of NOX activity by cell-free systems is often used to test potential inhibitors of the enzyme. A major drawback of this technique is the possible interferences between inhibitors and the probe, ferricytochrome c, used to measure the activity. We designed the "EquiNox2", a new pharmacological tool, to determine the direct interaction of potential inhibitors with equine phagocytic NOX and their effect on the enzyme activity or assembly. This method consists in binding the membrane fractions of neutrophils containing flavocytochrome b558 or the entire complex, reconstituted in vitro from membrane and cytosolic fractions of PMNs, onto the wells of a microplate followed by incubation with potential inhibitors or drugs. After incubation, the excess of the drug is simply eliminated or washed prior measuring the activity of the reconstituted complex. This latter step avoid the risk of interference between the inhibitor and the revelation solution and can distinguish if inhibitors, strongly bound or not, could interfere with the assembly of the enzymatic complex or with its activity. The EquiNox2 was validated using diphenyliodonium chloride and Gp91ds-tat, two well-known inhibitors largely described for human NADPH oxidase. The present technique was used to study and understand better the effect of curcumin and its water-soluble derivative, NDS27, on the assembly and activity of NOX. We demonstrated that curcumin and NDS27 can strongly bind to the enzyme and prevents its assembly making these molecules good candidates for the treatment of horse or human pathologies implying an excessive activation of neutrophils. [less ▲]

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See detailNDS27, the soluble derivative from curcumin binds to and inhibits myeloperoxidase
Franck, Thierry ULg; Derochette, Sandrine ULg; Zouaoui-Boudjeltia, Karim et al

Poster (2015, September 16)

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See detailModulatory effects of Ruthenium (II)-based complexes on oxidative stress induced by activated HL60 cells and Neutrophils
Mouithys-Mickalad, Ange ULg; Collienne, Simon ULg; Franck, Thierry ULg et al

Conference (2015, May 22)

There is a growing interest on the use of metal-based chemotherapeutic agents to fight different types of cancers [1]. The most used family of the organometallic compounds is platinum derivatives whose ... [more ▼]

There is a growing interest on the use of metal-based chemotherapeutic agents to fight different types of cancers [1]. The most used family of the organometallic compounds is platinum derivatives whose Cisplatin (CisPt) is the lead compound used for the treatment of various cancers including lung, testis, gastric, breast, etc. Nevertheless, beside its recognized therapeutic effects, side effects such as gastric toxicity and acute kidney failure were observed during the treatment, limiting its clinical use. Other compounds are currently studied and among them, Ruthenium (Ru) complexes have gained more importance for their less toxicity and lower aggressive effect on healthy tissues than CisPt. Ru-complexes are also more resorbed and excreted [2]. Numerous studies focused on the mechanisms of action of Ruthenium compounds to fight cancer, including antioxidant or pro-oxidant activity. During inflammation, activation and infiltration of neutrophils contribute to oxidant stress playing a crucial role in tumor development. Likewise, the degranulation of neutrophil causes the release of myeloperoxidase (MPO) which reacts with H2O2 to catalyze redox reactions. A therapeutic target to control inflammation is the modulation of oxidant enzymes and cells involved in radical species production and redox reactions. Because Ruthenium compounds can easily enter into cancer cells, a series of Ru(II)-complexes newly synthesized were used for this purpose. They were first tested for their radical scavenging activities using ABTS and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. Amongst them, compound 1 (LD0436) and compound 2 (LD04037) were then studied for their ability to modulate the reactive oxygen species (ROS) production by inflammatory cells like human promyelocytic leukemia cell line (HL 60) and neutrophils (PMN) using fluorescence, chemiluminescence (CL) and electron spin resonance ESR techniques. The toxicity of those Ru-complexes against HL-60 and neutrophils was checked using Trypan blue exclusion assay. Altogether, CL and ESR findings indicate that both complexes 1 (LD0436) and 2 (LD0437) exhibit a dose-dependent inhibitory activity compared to CisPt, gallic acid, curcumin and quercetin, which were taken as reference molecules in the different systems investigated. Similarly, the tested complexes also display an antioxidant profile on the substrate oxidation catalyzed by peroxidase such as MPO mainly involved in acute and chronic inflammatory situations. 1: (RuCl(p-Cymen)(S2C.IDip)]+(PF6)-], 2: (RuCl(p-Cymen)(S2C.Icy)]+(PF6)-] References: 1. Ceresa C, Brawin A, Cavaletti G, Trinidad A et al., (2014) Current Medicinal Chemistry 20(21), 2237-2265. 2. Liu, Y, Zhang X, Zhang R, et al., (2011) European Journal of Inorganic Chemistry. 1974-1980. [less ▲]

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See detailElectron paramagnetic resonance and fluorescence studies on potential anticancer properties of two new Ru(II) complexes : preliminary results
Collienne, Simon ULg; Terrak, Mohammed ULg; Mouithys-Mickalad, Ange ULg et al

Poster (2015, May 22)

Fight against cancer is a priority of today’s research. Since the discovery of the anticancer properties of cisplatin (CisPt) in 1965 by Rosenberg [1], the treatment of cancer by chemotherapy has known ... [more ▼]

Fight against cancer is a priority of today’s research. Since the discovery of the anticancer properties of cisplatin (CisPt) in 1965 by Rosenberg [1], the treatment of cancer by chemotherapy has known great improvements. Unfortunately, CisPt has several side effects and is not effective against all kinds of cancer. Nevertheless its use highlights the great potential of organometallic compounds in the treatment of cancer [2]. Here we investigated the potential anticancer properties of two new organometallic compounds based on ruthenium II : [RuCl(p-cymene)(S2C.IDip)]+(PF6)- and [RuCl(p-cymene)(S2C.ICy)]+(PF6)-, named as LDO436 and LDO437 respectively. [less ▲]

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See detailHDAC5 Depletion in Cancer Cells Induces an Oxidative Stress and Leads to a Metabolic Reprogramming toward Glucose and Glutamine Metabolism
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2015, February 11)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1 The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose and glutamine. Indeed, interference with both glucose and glutamine supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose or glutamine deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. Presenting author e-mail: elodie.hendrick@student.ulg.ac.be [less ▲]

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See detailHDAC5 Depletion in Cancer Cells Induces an Oxidative Stress and Leads to a Metabolic Reprogramming toward Glucose and Glutamine Metabolism
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2015, January 31)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1 The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose and glutamine. Indeed, interference with both glucose and glutamine supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose or glutamine deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. Presenting author e-mail: elodie.hendrick@student.ulg.ac.be [less ▲]

Detailed reference viewed: 21 (2 ULg)
See detailHDAC5 Depletion in Cancer Cells Induces an Oxidative Stress and Leads to a Metabolic Reprogramming toward Glucose and Glutamine Metabolism
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2015, January 27)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1 The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose and glutamine. Indeed, interference with both glucose and glutamine supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose or glutamine deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. Presenting author e-mail: elodie.hendrick@student.ulg.ac.be [less ▲]

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See detailAn immunological method to combine the measurement of active and total myeloperoxidase on the same biological fluid, and its application in finding inhibitors which interact directly with the enzyme.
Franck, Thierry ULg; Minguet, G.; Delporte, C. et al

in Free radical research (2015)

Myeloperoxidase (MPO) is a pro-oxidant enzyme involved in inflammation, and the measurement of its activity in biological samples has emerged essential for laboratory and clinical investigations. We will ... [more ▼]

Myeloperoxidase (MPO) is a pro-oxidant enzyme involved in inflammation, and the measurement of its activity in biological samples has emerged essential for laboratory and clinical investigations. We will describe a new method which combines the SIEFED (specific immunological extraction followed by enzymatic detection) and ELISA (ELISAcb) techniques to measure the active and total amounts of MPO on the same human sample and with the same calibration curve, as well as to define an accurate ratio between both the active and total forms of the enzyme. The SIEFED/ELISAcb method consists of the MPO extraction from aqueous or biological samples by immobilized anti-MPO antibodies coated onto microplate wells. After a washing step to eliminate unbound material, the activity of MPO is measured in situ by adding a reaction solution (SIEFED). Following aspiration of the reaction solution, a secondary anti-MPO antibody is added into the wells and the ELISAcb test is carried out in order to measure the total MPO content. To validate the combined method, a comparison was made with SIEFED and ELISA experiments performed separately on plasma samples isolated from human whole blood, after a neutrophil stimulation. The SIEFED/ELISAcb provides a suitable tool for the measurement of specific MPO activity in biological fluids and for the estimation of the inhibitory potential of a fluid. The method can also be used as a pharmacological tool to make the distinction between a catalytic inhibitor, which binds to MPO and inhibits its activity, and a steric inhibitor, which hinders the enzyme and prevents its immunodetection. [less ▲]

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See detailEffects of isoflurane and sevoflurane on the neutrophil myeloperoxidase system of horses
MINGUET, Grégory ULg; Franck, Thierry ULg; JORIS, Jean ULg et al

in Veterinary Immunology and Immunopathology (2015)

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See detailIdentification of Cytotoxic and Antioxidant Compounds from Allium gramineum Flowers
Mskhiladze, Lasha; Chincharadze, David; Tits, Monique ULg et al

in International Journal of Pharmaceutical Sciences and Drug Research (2015), 7

The present study evaluates the in vitro anticancer, antiplasmodial and antioxidant activity of the ethanolic crude extract from the flowers of Allium gramineum growing in Georgia and of one flavonol and ... [more ▼]

The present study evaluates the in vitro anticancer, antiplasmodial and antioxidant activity of the ethanolic crude extract from the flowers of Allium gramineum growing in Georgia and of one flavonol and two steroidal glycosides which were isolated from this plant. The flowers were extracted with ethanol and this total extract was subjected to successive bioguided fractionations to provide glycosides 1-3. Their structures were elucidated on the basis of NMR and ESI-MS spectrometric data in comparison with the existing literature and have been identified as: isorhamnetin-3-O-β-D-glucopyranoside (1), diosgenin-3-O-α-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (Prosapogenin A of dioscin) (2), diosgenin-3-O-α-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)-]-β-D-glucopyranoside (Deltonine) (3). The ethanolic extract has been shown to strongly inhibit the growth of breast adenocarcinoma cell lines, with an IC50 of 4.5 ± 0.7μg/mL for MDAMB-231 and 4.8 ± 0.9μg/mL for MCF-7 cells. The cytotoxic activity was related to 2 and 3 which exhibited potent cytotoxicity, with an IC50 of ± 3μM. Concerning antiplasmodial activities, only weak activities were observed using the ethanolic extract and the two saponins. The flavonoid was almost inactive. Finally, the radical-scavenging activity of the ethanolic extract was tested in presence of ABTS·+ solution. A decrease of the absorbance intensity was observed, with an IC50 value of 22.1 ± 0.6μg/mLwhile trolox, used as Standard drug, showed a pronounced activity (IC50 = 12.7±0.5μM). The glycoside 1 showed the lowest IC50 value of 20.1 ± 0.8μM while both 2 and 3 exhibited very weak radical scavenging activity. [less ▲]

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See detailMuscle Mitochondrial Dysfunction in Horses Affected by Acute Laminitis
Serteyn, Didier ULg; de la Rebière de Pouyade, Geoffroy ULg; Sandersen, Charlotte ULg et al

in Bioenergetics (2014)

Laminitis is a common and debilitating disease affecting horses and ponies. It often leads to the demise of the animal. Energy deficiency is suspected to entrain the disruption of the hemidesmosomes ... [more ▼]

Laminitis is a common and debilitating disease affecting horses and ponies. It often leads to the demise of the animal. Energy deficiency is suspected to entrain the disruption of the hemidesmosomes leading to the failure of the dermal-epidermal interface. The aim of this study was to measure the muscle mitochondrial function by high resolution respirometry. Muscle micro-biopsies were obtained from 11 horses affected by acute metabolic laminitis, 6 horses affected by acute laminitis resulting from a systemic inflammation response syndrome and 28 healthy horses distributed in 2 control groups: 17 horses with a body condition score [BSC, ranging from 0 (emaciated) to 5 (obese)] of 2 to 3 and 11 horses with a BSC of 4 to 5. During the acute phase of laminitis, a significant reduction of the muscle mitochondrial respiration was observed. The muscle mitochondrial dysfunction occurred independently of the etiology (metabolic disorder or systemic inflammation) leading to laminitis. The reduction of the oxidative phosphorylation and of the maximal respiratory capacity (after uncoupling) may induce depletion of the cell’s ATP content. If the same mitochondrial alteration occurs in the foot lamina, mitochondria targeting should be considered for the future, not only to better understand the physiopathology of the disease but also to maintain and to support the mitochondrial function before reaching the « mitochondrial dysfunction threshold » that may lead to the failure of the dermal-epidermal interface. [less ▲]

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See detailEvidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury
Quoilin, Caroline ULg; Mouithys-Mickalad, Ange ULg; Lécart, Sandrine et al

in Biochimica et Biophysica Acta-Bioenergetics (2014), 1837(10), 1790-1800

To investigate the role of oxidative stress and/or mitochondrial impairment in the occurrence of acute kidney injury (AKI) during sepsis, we developed a sepsis-induced in vitro model using proximal ... [more ▼]

To investigate the role of oxidative stress and/or mitochondrial impairment in the occurrence of acute kidney injury (AKI) during sepsis, we developed a sepsis-induced in vitro model using proximal tubular epithelial cells exposed to a bacterial endotoxin (lipopolysaccharide, LPS). This investigation has provided key features on the relationship between oxidative stress and mitochondrial respiratory chain activity defects. LPS treatment resulted in an increase in the expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX-4), suggesting the cytosolic overexpression of nitric oxide and superoxide anion, the primary reactive nitrogen species (RNS) and reactive oxygen species (ROS). This oxidant state seemed to interrupt mitochondrial oxidative phosphorylation by reducing cytochrome c oxidase activity. As a consequence, disruptions in the electron transport and the proton pumping across the mitochondrial inner membrane occurred, leading to a decrease of the mitochondrial membrane potential, a release of apoptotic-inducing factors and a depletion of adenosine triphosphate. Interestingly, after being targeted by RNS and ROS, mitochondria became in turn producer of ROS, thus contributing to increase the mitochondrial dysfunction. The role of oxidants in mitochondrial dysfunction was further confirmed by the use of iNOS inhibitors or antioxidants that preserve cytochrome c oxidase activity and prevent mitochondrial membrane potential dissipation. These results suggest that sepsis-induced AKI should not only be regarded as failure of energy status but also as an integrated response, including transcriptional events, ROS signaling, mitochondrial activity and metabolic orientation such as apoptosis. [less ▲]

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See detailHDAC5 Depletion in Cancer Cells Induces an Oxidative Stress and Leads to a Metabolic Reprogramming toward Glucose and Glutamine Metabolism
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Conference (2014, September 30)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1 The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glycolysis and glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. Presenting author e-mail: elodie.hendrick@student.ulg.ac.be [less ▲]

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See detailHDAC5 Depletion in Cancer Cells Induces an Oxidative Stress and Leads to a Metabolic Reprogramming toward Glucose and Glutamine Metabolism
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2014, September 25)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1 The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glycolysis and glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. Presenting author e-mail: elodie.hendrick@student.ulg.ac.be [less ▲]

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See detailGlucose-dependent metabolic reprogramming in HDAC5-depleted cancer cells
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2014, May 19)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1 The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glycolysis and glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. Presenting author e-mail: elodie.hendrick@student.ulg.ac.be [less ▲]

Detailed reference viewed: 20 (0 ULg)
See detailGlucose-dependent metabolic reprogramming in HDAC5-depleted cancer cells
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2014, April 25)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival (PEIXOTO et al., 2012). The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glycolysis and glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. Acknowledgements This work fiancially suppoted by a grant of F.R.S .-FNRS (contract n° 7.4515.12F). E Hendrick is recipient of a Televie fellowship. References PEIXOTO et al., (2012) Cell Death and Differentiation. 7:1239-52. [less ▲]

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See detailComplex I Mitochondrial Dysfunction in HDAC5-depleted Cancer Cells Induces Glucose-dependent Metabolic Reprogramming
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2014, February 01)

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure ... [more ▼]

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1. Aims : The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Methods and results : Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of NDUFB5, a subunit of the complex I of the mitochondrial respiratory chain through modulation of mRNA stability. HDAC5 depletion-induced NDUFB5 downregulation causes a significant increase of ROS production and induces uncoupled mitochondrial respiration. In addition, this HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Conclusions : Our study demonstrated for the first time that specific HDAC5 inhibition induces alteration of NDUFB5 gene expression by altering mRNA stability and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. [less ▲]

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See detailComplex I Mitochondrial Dysfunction in HDAC5-depleted Cancer Cells Induces Glucose-dependent Metabolic Reprogramming
Hendrick, Elodie ULg; Peixoto, Paul ULg; Matheus, Nicolas ULg et al

Poster (2014, January 27)

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure ... [more ▼]

Introduction : Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1. Aims : The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Methods and results : Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of NDUFB5, a subunit of the complex I of the mitochondrial respiratory chain through modulation of mRNA stability. HDAC5 depletion-induced NDUFB5 downregulation causes a significant increase of ROS production and induces uncoupled mitochondrial respiration. In addition, this HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose. Indeed, interference with glucose supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Conclusions : Our study demonstrated for the first time that specific HDAC5 inhibition induces alteration of NDUFB5 gene expression by altering mRNA stability and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. [less ▲]

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