References of "Mouithys-Mickalad, Ange"
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See detailComparison of metabolic profiles and bioactivities of the leaves of three edible Congolese Hibiscus species
Kapepula, Paulin Mutwale; Kabamba Ngombe, Nadege; Tshisekedi Tshibangu, Pascal et al

in Natural Product Research (2017), 6419(March), 1--8

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See detailAntiplasmodial activity of Heinsia crinita (Rubiaceae) and identification of new iridoids.
Tshisekedi Tshibangu, P.; Mutwale Kapepula, P.; Kabongo Kapinga, M. J. et al

in Journal of Ethnopharmacology (2017), 196

ETHNOPHARMACOLOGICAL RELEVANCE: Heinsia crinita is used in traditional medicine for the treatment of febrile illness and erectile dysfunction. Its stem bark powder is found in some peripheral markets in ... [more ▼]

ETHNOPHARMACOLOGICAL RELEVANCE: Heinsia crinita is used in traditional medicine for the treatment of febrile illness and erectile dysfunction. Its stem bark powder is found in some peripheral markets in the Democratic Republic of the Congo (DRC) as a remedy against malaria. Investigations were conducted on crude extracts of leaves, fruits and stem barks in view to validate their use and to determine which plant part possesses the best antiplasmodial properties. MATERIALS AND METHODS: Different plant parts were extracted with methanol, ethanol and dichloromethane. Based on the preliminary assays, the dichloromethane extract of the stem bark was subjected to fractionation using preparative HPLC system and column chromatography. This step led to the isolation of two new iridoids which had their structures elucidated by NMR, UV, MS and FT-IR spectroscopic techniques. Extracts and pure compounds were tested in vitro against the 3D7 strain of Plasmodium falciparum. The inhibition of the parasite growth was evaluated in vitro by colorimetric method (p-LDH assay) and their cytotoxicity evaluated in vitro against the human non-cancer fibroblast cell line (WI38) through WST1 assay. The in vivo antiplasmodial activity was assessed by the inhibition of Plasmodium berghei growth in infected mice treated with the ethanol extract of H. crinita stem bark at the concentrations of 200 and 300mg/Kg/day per os, using a protocol based on the 4-d suppressive test of Peters and compared to a non-treated negative control group of mice (growth =100%). Finally the antioxidant activity of the same extract was evaluated using ABTS, DPPH and cell-based assays. RESULTS: A moderate in vitro antiplasmodial activity was observed for the dichloromethane extract of the stem bark of H. crinita (IC50 =29.2+/-1.39microg/mL) and for the two new iridoids, lamalbide 6, 7, 8- triacetate (IC50 =16.39+/-0.43microg/mL) as well as for its aglycone lamiridosin 6, 7, 8-triacetate (IC50 =0.44.56+/-1.12microg/mL). The ethanolic stem bark extract (200 and 300mg/kg/day, oral route) showed a moderate in vivo antimalarial activity in Plasmodium berghei-infected mice with 27.84+/-2.75% and 48.54+/-3.76% of inhibition of the parasite growth, respectively (p<0.01).). This extract displayed high cellular antioxidant activity using dichlorofluorescein-diacetate (DCFDA) on HL-60 monocytes. These crude extracts and pure compounds tested at the higher concentration of 100microg/mL did not show any cytotoxicity against WI38 cells. CONCLUSIONS: The results showed that H. crinita extracts possess antimalarial activity and contain some unusual iridoids with moderate antiplasmodial activity, therefore justifying to some extent its traditional use by the local population in DRC for this purpose. This is the first report of the isolation and antiplasmodial activity of these two new iridoids. [less ▲]

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See detailMyoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer
Blomme, Arnaud; Costanza, Brunella ULg; De Tullio, Pascal ULg et al

in Oncogene (2016)

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as ... [more ▼]

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes. Using a combination of proteomics, metabolomics and electron microscopy, we demonstrate that myoferlin depletion results in marked alteration of endosomal system and metabolism. Mechanistically, myoferlin depletion caused impaired vesicle traffic that led to a misbalance of saturated/unsaturated fatty acids. This provoked mitochondrial dysfunction in TNBC cells. As a consequence of the major metabolic stress, TNBC cells rapidly triggered AMP activated protein kinase-mediated metabolic reprogramming to glycolysis. This reduced their ability to balance between oxidative phosphorylation and glycolysis, rendering TNBC cells metabolically inflexible, and more sensitive to metabolic drug targeting in vitro. In line with this, our in vivo findings demonstrated a significantly reduced capacity of myoferlin-deficient TNBC cells to metastasise to lungs. The significance of this observation was further supported by clinical data, showing that TNBC patients whose tumors overexpress myoferlin have worst distant metastasis-free and overall survivals. This novel insight into myoferlin function establishes an important link between vesicle traffic, cancer metabolism and progression, offering new diagnostic and therapeutic concepts to develop treatments for TNBC patients. [less ▲]

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See detailValorization of Seeds from Some Field Border Flowering Seeds
Paul, Aman ULg; Danthine, Sabine ULg; Mutwale Kapepula, Paulin ULg et al

Poster (2016, September 20)

Flowering strips are now being increasingly cultivated along the fields to improve biodiversity. However after serving for the desired function, these plants have no utilization besides animal feed. It ... [more ▼]

Flowering strips are now being increasingly cultivated along the fields to improve biodiversity. However after serving for the desired function, these plants have no utilization besides animal feed. It could be really interesting to valorize some commonly grown plant in these strips to render food or health promoting compounds. With this objective in mind the seeds of Achillea millefolium, Anthriscus sylvestris and Prunella vulgaris were investigated for lipids, proteins and phenolic content. Further the lipids were analyzed for fatty acid profile using gas chromatography and the phenolic compounds in the methanolic extract of defatted seeds were identified using HPLC-DAD. The antiradical activity of the methanolic extracts obtained from defatted seeds was investigated using DPPH and ABTS assays. The anti-inflammatory potential of these seed extracts was evaluated on the reactive oxygen species (ROS) production by stimulated neutrophils and on the specific activity of myeloperoxidase (MPO), a pro-oxidant enzyme marker of inflammation. Seeds from all three plants were analyzed with interesting levels of lipids, proteins and phenolic content. Linoleic acid, oleic acid and alpha-linolenic acid were the major fatty acids analyzed in A. millefolium, A. sylvestris and P. vulgaris respectively. On the other hand different phenolic acid formed the major phenolic constituents. Seed extracts displayed high ABTS and DPPH radical-scavenging activities in a dose dependent manner. Also a strong dose dependent anti-inflammatory activity of all three extracts was observed against ROS production by neutrophils and MPO activity. Results indicate that these seed show a great potential to render lipids which could be utilized as human food, further the defatted seeds could be directly included in human diet due to interesting levels of proteins and anti-inflammation ability. [less ▲]

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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 detailAntioxidant potentiality of three herbal teas consumed in Bandundu rural areas of Congo.
Mutwale Kapepula, Paulin ULg; Mbombo Mungitshi, Patricia; Franck, Thierry ULg et al

in Natural Product Research (2016)

The aim of this study was to evaluate and compare the cellular antioxidant activities of Lantana montevidensis, Lippia multiflora, and Ocimum gratissimum leaves often consumed as herbal teas in a rural ... [more ▼]

The aim of this study was to evaluate and compare the cellular antioxidant activities of Lantana montevidensis, Lippia multiflora, and Ocimum gratissimum leaves often consumed as herbal teas in a rural area of Bandundu severely affected by konzo, which is related to oxidative damage. Consequently, dietary supplements with proven antioxidant potentialities could be of real interest to promote in this area. Phytochemical screening by TLC and HPLC-DAD of extracts revealed the presence of verbascoside as a major phenolic compound. Verbascoside in L. montevidensis and O. gratissimum is reported here for the first time. All extracts displayed high ABTS and DPPH radical-scavenging activities at the concentration range of 1-40 mug mL-1 according to order: L. multiflora > O. gratissimum > L. montevidensis. L. multiflora showed the best cellular antioxidant activity using DCFH-DA on HL-60 monocytes assay at 1-20 mug mL-1. These herbal teas may be used as nutraceuticals for their potent antioxidant activity. [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 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 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 ▲]

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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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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)

Detailed reference viewed: 34 (10 ULg)