References of "Serteyn, Didier"
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See detailMitochondrial function and aerobic capacity assessed by high resolution respirometry in Thoroughbred horses
Serteyn, Didier ULg; Ceusters, Justine ULg; Nonnenmacher et al

in Comparative Exercise Physiology (2016), 12(2), 67-73

During the initial stages of training of young Thoroughbred horses, low intensity exercise is employed to increase aerobic capacity. High Resolution Respirometry (HRR) allows the determination of aerobic ... [more ▼]

During the initial stages of training of young Thoroughbred horses, low intensity exercise is employed to increase aerobic capacity. High Resolution Respirometry (HRR) allows the determination of aerobic capacities in small samples of permeabilised muscle fibres. The aim of the study was to measure the mitochondrial function by HRR in Thoroughbred horses, to compare these values to Warmblood horses and to evaluate the effect of a 10-weeks training period. The mitochondrial function was measured by HRR using different substrate-uncoupler protocols (SUIT 1 and 2) in muscle microbiopsies from two groups of untrained horses: 17 Warmblood and 8 Thoroughbred and in the group of 8 Thoroughbred horses before and after a 10-week training period. The SUIT1 protocol employed to compare the two groups of horses showed that in Thoroughbred horses, the mean values for oxygen flux expressed as tissue mass-specific respiration were significantly higher for complex I (CI)Glutamate+Malate, CI + complex II, and maximum electron transport capacities (ETSmax) than the mean values measured in Warmblood horses. The SUIT 1 and SUIT 2 protocols revealed large differences among Thoroughbred horses before and after training. The SUIT 2 protocols showed a significant difference for the complex I activity before and after training but only when the oxygen flux was expressed as percentage of ETSmax. This study shows the interest of HRR in equine sport medicine and exercise physiology, but shows that the technique requires further refinement. Indeed significant differences have been shown between the Thoroughbred and the Warmblood horses highlighting the need to have baseline data for each breed. The Thoroughbred horses had globally a high oxidative phosphorylation capacity with an increase of CI activity induced by an aerobic training program. [less ▲]

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See detailStudy of the antioxidant action of morphine on the peroxidase cycle of MPO and HRP
Hoebeke, Maryse ULg; Nyssen, Pauline ULg; Franck, Thierry ULg et al

Poster (2016, May 20)

Besides its analgesic action, morphine presents antioxidants properties and therefore an interest as inhibitor of MPO. Moreover, it has been proved that morphine can inhibit the ROS production and the PMN ... [more ▼]

Besides its analgesic action, morphine presents antioxidants properties and therefore an interest as inhibitor of MPO. Moreover, it has been proved that morphine can inhibit the ROS production and the PMN degranulation. Therefore, it seems like morphine has a direct action on MPO activities but the exact mechanism of action is still to be elucidated. The aim of the study is to investigate the potential antioxidant activity of morphine on the peroxidation cycle of MPO, in comparison to another peroxidase, Horseradish Peroxidase (HRP). [less ▲]

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See detailMitochondrial function is altered in horse atypical myopathy
Lemieux, Hélène; BOEMER, François ULg; van Galen, Gaby et al

in Mitochondrion (2016), 30

Equine atypical myopathy in Europe is a fatal rhabdomyolysis syndrome that results from the ingestion of hypoglycin A contained in seeds and seedlings of Acer pseudoplatanus. The hallmark of atypical ... [more ▼]

Equine atypical myopathy in Europe is a fatal rhabdomyolysis syndrome that results from the ingestion of hypoglycin A contained in seeds and seedlings of Acer pseudoplatanus. The hallmark of atypical myopathy consists of a severe alteration in the energy metabolism including a severe impairment in muscle mitochondrial respiration that could contribute to its high death rate [less ▲]

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See detailPolyphenols from Silybum marianum inhibit in vitro the oxidant response of equine neutrophils and myeloperoxidase activity.
Zholobenko, A.; Mouithys-Mickalad, Ange ULg; Modriansky, M. et al

in Journal of Veterinary Pharmacology & Therapeutics (2016)

A recent study showed that silymarin, a standardized extract of S. marianum might be used in the prevention of equine laminitis. We investigated the effects of quercetin and some compounds found in ... [more ▼]

A recent study showed that silymarin, a standardized extract of S. marianum might be used in the prevention of equine laminitis. We investigated the effects of quercetin and some compounds found in silymarin (silybin, taxifolin and dehydrosilybin) on reactive oxygen species (ROS) production and myeloperoxidase (MPO) release by stimulated equine neutrophils (PMNs) and on MPO activity. All compounds (tested between 100 nm and 100 mum) inhibited superoxide anion production by stimulated PMNs in a dose-dependent manner. Dehydrosilybin and quercetin inhibited superoxide production and MPO release from 10 mum. Classical MPO assay showed quercetin as the most potent inhibitor, followed by taxifolin, dehydrosilybin and silybin. SIEFED MPO assay highlighting the binding of tested compounds to MPO showed that only quercetin and taxifolin maintained an efficient inhibition above 90% at 10 mum. Altogether, our results showed a strong inhibition of PMN activation by planar compounds such as quercetin and dehydrosilybin and a strong inhibition of MPO activity by the smallest molecules, quercetin and taxifolin. In conclusion, the compounds from silymarin may be useful for modulating the oxidative response of PMNs, involved in the pathogenesis of laminitis, but further in vivo studies are needed. [less ▲]

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See detailSubstitution of egg yolk by a cyclodextrin-cholesterol complex allows a reduction of the glycerol concentration into the freezing medium of equine sperm.
Blommaert, Didier; Franck, Thierry ULg; Donnay, Isabelle et al

in Cryobiology (2016), 72(1), 27-32

The aim of this work was to completely replace the egg yolk a classical diluent for freezing equine semen by a cyclodextrin-cholesterol complex. At the same time, the reduction in the glycerol content ... [more ▼]

The aim of this work was to completely replace the egg yolk a classical diluent for freezing equine semen by a cyclodextrin-cholesterol complex. At the same time, the reduction in the glycerol content used for cryopreservation and the incubation time between sperm and the freezing media were evaluated. Horse ejaculates were frozen with four different freezing extenders: a frozen reference medium (IF) containing egg yolk and 2.5% glycerol and media without egg yolk but supplemented with 1.5 mg 2-hydroxypropyl-beta-cyclodextrin cholesterol (HPbetaCD-C) complex and containing either 1% (G1), 2% (G2) or 3% glycerol (G3). Three incubation times (90, 120 and 180 min) at 4 degrees C between the fresh semen and the different media were tested before freezing. Viability and motility analyses were performed with computer assisted semen analysis (CASA). Results showed that the freezing media containing the HPbetaCD-C complex with 1%, 2% and 3% glycerol significantly improve the 3 in vitro parameters of post thawing semen quality (viability, progressive and total mobilities) compared to IF. The best improvement of the parameters was obtained with G1 medium and the longest contact time. The substitution of egg yolk by HPbetaCD-C complex allows the decrease of protein charge of the medium while favouring the cholesterol supply to membrane spermatozoa offering it a better resistance to osmotic imbalance and a better tolerance to the glycerol toxicity. Our results highlight that the egg yolk of an extender for the freezing of horse semen can be completely substituted by HPbetaCD-C complex. [less ▲]

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See detailLongitudinal Study of Growth and Osteoarticular Status in Foals Born to Between-Breed Embryo Transfers
Peugnet, Pauline; Mendoza García, Luis ULg; Wimel, Laurence et al

in Journal of Equine Veterinary Science (2016), 37

The role of antenatal events on growth and predisposition to osteochondrosis (OC) was investigated in foals born to between-breed embryo transfers. Pony (P), saddlebred (S), and draft (D) horses were used ... [more ▼]

The role of antenatal events on growth and predisposition to osteochondrosis (OC) was investigated in foals born to between-breed embryo transfers. Pony (P), saddlebred (S), and draft (D) horses were used. Control P-P (n ¼ 21) and S-S (n ¼ 28) pregnancies were obtained by artificial insemination. Enhanced and restricted pregnancies were obtained by transferring P or S embryos into D mares (P-D, n ¼ 6 and S-D, n ¼ 8) and S embryos into P mares (S-P, n ¼ 6), respectively. Control and experimental foals were raised by their dams and recipient mothers, respectively, and weaned at age 6 months. Body measurements were recorded from birth to age 18 months. Osteochondrosis status was evaluated shortly after weaning and at age 18 months. Fetal growth was enhanced in P-D foals with overgrowth of most body segments until age 18 months. Fetal growth was restricted in S-P foals compared with S-D foals. Body weight, shoulder, and hip width of S-P foals grew slower before weaning but subsequently caught up after weaning. Other segments did not catch up, resulting in reduced body weight and withers’ height in S-P compared with S-D foals at age 18 months. The relative risk of developing OC was increased in restricted S-P foals compared with S-S and S-D foals shortly after weaning where all S-P foals were OC positive. Only two S-P foals were still OC positive at age 18 months. These data confirm the impact of the intrauterine environment on growth, skeletal health, and possibly athletic capacities of horses. [less ▲]

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See detailImpact of feeding and housing on the development ofosteochondrosis in foals—A longitudinal study
Mendoza García, Luis ULg; Lejeune, Jean-Philippe ULg; Caudron, Isabelle ULg et al

in Preventive Veterinary Medicine (2016), 127

Osteochondrosis dissecans (OCD) is a developmental orthopedic disease caused by a failure of the endochondral ossification in epiphyseal plates and joint cartilage. This trouble may induce the presence of ... [more ▼]

Osteochondrosis dissecans (OCD) is a developmental orthopedic disease caused by a failure of the endochondral ossification in epiphyseal plates and joint cartilage. This trouble may induce the presence of osteochondral fragments in the articulation, fissures or subchondral bone cysts in the growth cartilage. Occurrence of osteochondrosis is influenced by a complex interaction of different factors. Among these, the effect of the housing and the feeding of the foals during their first months of life, have been described as risk factors for the development of osteochondrosis. The aim of this study was to investigate the evolution of OCD lesions with a longitudinal study in 204 young foals from 6 to 18 months in comparison to the type of feeding and the type of housing conditions. These factors and OCD status were obtained by a questionnaire and radiological examination, respectively. This allowed dividing the foals into four groups according to the initial OCD status and the evolution of the condition. As a result, we found that foals fed with concentrates show a higher probability to develop OCD lesions (p = 0.06), while foals not receiving concentrates, had a higher probability to heal from existing OCD lesions (p = 0.001). This study supports the theory that management factors such as feeding or housing may influence the evolution of the osteochondrosis disease. [less ▲]

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See detailCompensatory Metabolism Promotes Cancer Cell Adaptation to HDAC5 Silencing
Hendrick, Elodie ULg; Peixoto, Paul; Polese, Catherine et al

Poster (2015, December 03)

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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 detailMammalian muscle-derived stem cells
Serteyn, Didier ULg; Ceusters, Justine ULg

Patent (2015)

The present invention provides a new method of obtaining muscle-derived mesenchymal stem cells from microbiopsies of mammalian origin. The invention provides for a minimally invasive methodology yielding ... [more ▼]

The present invention provides a new method of obtaining muscle-derived mesenchymal stem cells from microbiopsies of mammalian origin. The invention provides for a minimally invasive methodology yielding high amounts of MSCs that can differentiate into different cell lineages. [less ▲]

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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 detailDevelopment and evaluation in vitro and in vivo of injectable hydrolipidic gels with sustained-release properties for the management of articular pathologies such as osteoarthritis.
Réeff, Jonathan; Oprenyeszk, Frédéric ULg; Franck, Thierry ULg et al

in International Journal of Pharmaceutics (2015), 490

This study aimed to evaluate glycerol monooleate (GMO) as a carrier to develop viscoelastic and injectable sustained-release drug delivery systems. The potential pro- and antioxidant activity of the ... [more ▼]

This study aimed to evaluate glycerol monooleate (GMO) as a carrier to develop viscoelastic and injectable sustained-release drug delivery systems. The potential pro- and antioxidant activity of the developed hydrolipidic gels were evaluated by measuring the production of ROS by polymorphonuclear leukocytes (PMNs). In addition, the biocompatibility and effectiveness of two selected gel candidates were evaluated in vivo by evaluating the benefit of a single intraarticular injection of these new treatments in a model of osteoarthritis in rabbits. The in vitro study demonstrated that the carrier F1 did not have a pro-oxidative effect and even protected PMNs against natural auto-activation, regardless of the incorporation of either clonidine chlorhydrate or betamethasone dipropionate. The in vivo study demonstrated that F1 and F1-BDP induced a loss of cartilage quality in comparison to the control and reference groups but that the lesions of cartilage observed were generally mild, with not much full-depth erosion. Moreover, no exacerbating inflammation was observed when considering the synovial membranes and the PGE2 and CRP levels. These results seemed to demonstrate that the sustained-release formulation based on GMO could be well-tolerated after intraarticular injection. Moreover, it could have the potential to prevent inflammatory conditions while sustaining drug activity locally over weeks. [less ▲]

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See detailAge-dependent expression of osteochondrosis-related genes in equine leukocytes
Mendoza García, Luis ULg; Piquemal, David; Lejeune, Jean-Philippe ULg et al

in Veterinary Record : Journal of the British Veterinary Association (2015), 2

Introduction: Osteochondrosis (OC) is a developmental disease in horses which has a significant impact on the horse’s welfare and performance. The early disturbance in the process of endochondral ... [more ▼]

Introduction: Osteochondrosis (OC) is a developmental disease in horses which has a significant impact on the horse’s welfare and performance. The early disturbance in the process of endochondral ossification progresses to inflammatory and repair processes in older horses. Previously, differentially expressed genes in leukocytes of OC-affected horses have been identified. The aim of the present study is to detect age-related changes in these differentially expressed genes. Materials and Methods: The expression of OC-related genes was analysed by real-time PCR and subsequent statistical analysis (ΔΔCT) in the leukocytes of 135 Belgian Warmblood horses divided into three different age groups: 30 months (n=38). Results: Relative expression of genes of horses less than 12 months of age showed significant induction of the genes MGAT4A, PRKCG, MHCI, ApoB, ApoB3G, B4GALT6 and a significantly lower expression of the genes OAS3. Horses of 18–24 months of age, showed a significantly higher expression of the genes TBC1D9, MGAT4A, IFIH1, MHCIIa and MMP1. Horses of more than 30 months of age showed a significantly higher expression of the genes MGAT4A, HP, SECTM1 compared with their age-matched control groups. Conclusions: The study demonstrates that OC-related genes are differentially expressed in horses of different ages compared with their age-matched controls. Some of the genes may be implicated in cell signalling and differentiation as well as carbohydrate and lipid metabolism and inflammation. However, the causal relationship between the differentially expressed genes and the development and progression of the OC lesions needs to be determined. [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 ▲]

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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 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 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 (2015)

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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