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25 results on '"Spincemaille, Pieter"'

1. Correction: The ribosomal RPL10 R98S mutation drives IRES-dependent BCL-2 translation in T-ALL

Author

Kampen, Kim R., Sulima, Sergey O., Verbelen, Benno, Girardi, Tiziana, Vereecke, Stijn, Fancello, Laura, Rinaldi, Gianmarco, Verbeeck, Jelle, Op de Beeck, Joyce, Uyttebroeck, Anne, Meijerink, Jules P. P., Moorman, Anthony V., Harrison, Christine J., Spincemaille, Pieter, Cools, Jan, Cassiman, David, Fendt, Sarah-Maria, Vermeersch, Pieter, and De Keersmaecker, Kim

Published
2019
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4. Roux-en-y gastric bypass attenuates hepatic mitochondrial dysfunction in mice with non-alcoholic steatohepatitis

Author

Verbeek, Jef, Lannoo, Matthias, Pirinen, Eija, Ryu, Dongryeol, Spincemaille, Pieter, Vander Elst, Ingrid, Windmolders, Petra, Thevissen, Karin, Cammue, Bruno P A, van Pelt, Jos, Fransis, Sabine, Van Eyken, Peter, Ceuterick-De Groote, Chantal, Van Veldhoven, Paul P, Bedossa, Pierre, Nevens, Frederik, Auwerx, Johan, and Cassiman, David

Published
2015
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6. Repurposing AM404 for the treatment of oral infections by Porphyromonas gingivalis : Antibacterial activity and mode of action of AM404

Author

Gerits, Evelien, Spincemaille, Pieter, De Cremer, Kaat, De Brucker, Katrijn, Beullens, Serge, Thevissen, Karin, Cammue, Bruno PA, Vandamme, Katleen, Fauvart, Maarten, Verstraeten, Natalie, and Michiels, Jan

Subjects
AM404, N-(4-hydroxyphenyl)-arachidonylamide, biofilms, Porphyromonas gingivalis, periodontitis, peri-implantitis
Abstract

Porphyromonas gingivalis is a major pathogen involved in oral diseases such as periodontitis and peri-implantitis. Management of these diseases typically includes mechanical debridement of the colonized surfaces followed by application of antiseptics or antibiotics. Disadvantages associated with the use of antiseptics and the growing worldwide problem of antibiotic resistance have necessitated the search for alternative agents. In this study, the antibacterial and antibiofilm properties of AM404, an active metabolite of paracetamol, were tested against P. gingivalis and other bacterial pathogens. The activity of AM404 was tested against 10 bacteria, including both oral and nonoral human pathogens. The minimal inhibitory concentration (MIC) of AM404 was determined by measuring optical density (OD) values. The minimum biofilm inhibitory concentration (MBIC) was detected by crystal violet staining. The activity of structural analogs of AM404 was tested by MIC determinations. The effect of AM404 on P. gingivalis biofilms formed on titanium disks as a model for dental implants was evaluated by colony forming unit counting. Potential cytotoxicity of AM404 towards HEK-293 (human embryonic kidney cells), HepG2 (human hepatoma cells), IEC-6 (rat intestinal cells), and Panc-1 cells (pancreatic cancer cells) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. To get more insight in the mode of action of AM404, we used the fluorescent dyes N-phenyl-1-napthylamine and SYTOX green to investigate outer and inner membrane damage of P. gingivalis induced by AM404, respectively. Of all tested pathogens, AM404 only inhibited growth and biofilm formation of P. gingivalis. Moreover, it showed potent activity against P. gingivalis biofilms formed on titanium surfaces. A structure-activity analysis demonstrated that the unsaturated carbon chain is essential for its antibacterial activity. Importantly, AM404 was not toxic towards the tested mammalian cells up to concentrations approaching 4× the MIC. Membrane damage assays using fluorescent probes N-phenyl-1-napthylamine and SYTOX green revealed that membrane permeabilization presumably is the primary antibacterial mode of action of AM404. Collectively, our results suggest that AM404 has the potential to be used for the development of new drugs specifically targeting P. gingivalis-related infections. ispartof: CLINICAL AND EXPERIMENTAL DENTAL RESEARCH vol:3 issue:2 pages:69-76 ispartof: location:United States status: published

Published
2017

7. The ribosomal RPL10 R98S mutation drives IRES-dependent BCL-2 translation in T-ALL

Author

Kampen, Kim R., primary, Sulima, Sergey O., additional, Verbelen, Benno, additional, Girardi, Tiziana, additional, Vereecke, Stijn, additional, Rinaldi, Gianmarco, additional, Verbeeck, Jelle, additional, Op de Beeck, Joyce, additional, Uyttebroeck, Anne, additional, Meijerink, Jules P. P., additional, Moorman, Anthony V., additional, Harrison, Christine J., additional, Spincemaille, Pieter, additional, Cools, Jan, additional, Cassiman, David, additional, Fendt, Sarah-Maria, additional, Vermeersch, Pieter, additional, and De Keersmaecker, Kim, additional

Published
2018
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8. Identification of survival-promoting OSIP108 peptide variants and their internalization in human cells

Author

Verbandt, Sara, Troeira Henriques, Sonia, Spincemaille, Pieter, Harvey, Peta, Chandhok, Gursimran, Sauer, Vanessa, De Coninck, Barbara, Cassiman, David, Craik, David, Cammue, Bruno, De Cremer, Kaat, Thevissen, Karin, Verbandt, Sara, Troeira Henriques, Sonia, Spincemaille, Pieter, Harvey, Peta, Chandhok, Gursimran, Sauer, Vanessa, De Coninck, Barbara, Cassiman, David, Craik, David, Cammue, Bruno, De Cremer, Kaat, and Thevissen, Karin

Abstract

he plant-derived decapeptide OSIP108 increases tolerance of yeast and human cells to apoptosis-inducing agents, such as copper and cisplatin. We performed a whole amino acid scan of OSIP108 and conducted structure-activity relationship studies on the induction of cisplatin tolerance (CT) in yeast. The use of cisplatin as apoptosis-inducing trigger in this study should be considered as a tool to better understand the survival-promoting nature of OSIP108 and not for purposes related to anti-cancer treatment. We found that charged residues (Arg, His, Lys, Glu or Asp) or a Pro on positions 4-7 improved OSIP108 activity by 10% or more. The variant OSIP108[G7P] induced the most pronounced tolerance to toxic concentrations of copper and cisplatin in yeast and/or HepG2 cells. Both OSIP108 and OSIP108[G7P] were shown to internalize equally into HeLa cells, but at a higher rate than the inactive OSIP108[E10A], suggesting that the peptides can internalize into cells and that OSIP108 activity is dependent on subsequent intracellular interactions. In conclusion, our studies demonstrated that tolerance/survival-promoting properties of OSIP108 can be significantly improved by single amino acid substitutions, and that these properties are dependent on (an) intracellular target(s), yet to be determined.

Published
2017

10. Dietary intervention, but not losartan, completely reverses non-alcoholic steatohepatitis in obese and insulin resistant mice

Author

Verbeek, Jef, primary, Spincemaille, Pieter, additional, Vanhorebeek, Ilse, additional, Van den Berghe, Greet, additional, Vander Elst, Ingrid, additional, Windmolders, Petra, additional, van Pelt, Jos, additional, van der Merwe, Schalk, additional, Bedossa, Pierre, additional, Nevens, Frederik, additional, Cammue, Bruno, additional, Thevissen, Karin, additional, and Cassiman, David, additional

Published
2017
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11. Identification of survival-promoting OSIP108 peptide variants and their internalization in human cells

Author

Verbandt, Sara, primary, Henriques, Sónia Troeira, additional, Spincemaille, Pieter, additional, Harvey, Peta J., additional, Chandhok, Gursimran, additional, Sauer, Vanessa, additional, De Coninck, Barbara, additional, Cassiman, David, additional, Craik, David J., additional, Cammue, Bruno P.A., additional, De Cremer, Kaat, additional, and Thevissen, Karin, additional

Published
2017
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12. Increasing the Fungicidal Action of Amphotericin B by Inhibiting the Nitric Oxide-Dependent Tolerance Pathway

Author

Vriens, Kim, primary, Kumar, Phalguni Tewari, additional, Struyfs, Caroline, additional, Cools, Tanne L., additional, Spincemaille, Pieter, additional, Kokalj, Tadej, additional, Sampaio-Marques, Belém, additional, Ludovico, Paula, additional, Lammertyn, Jeroen, additional, Cammue, Bruno P. A., additional, and Thevissen, Karin, additional

Published
2017
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13. Dual loss of succinate dehydrogenase (SDH) and complex I activity is necessary to recapitulate the metabolic phenotype of SDH mutant tumors

Author

Lorendeau, Doriane, Rinaldi, Gianmarco, Boon, Ruben, Spincemaille, Pieter, Metzger, Kristine, Jäger, Christian, Christen, Stefan, Dong, Xiangyi, Kuenen, Sabine, Voordeckers, Karin, Verstreken, Patrik, Cassiman, David, Vermeersch, Pieter, Verfaillie, Catherine, Hiller, Karsten, Fendt, Sarah-Maria, Lorendeau, Doriane, Rinaldi, Gianmarco, Boon, Ruben, Spincemaille, Pieter, Metzger, Kristine, Jäger, Christian, Christen, Stefan, Dong, Xiangyi, Kuenen, Sabine, Voordeckers, Karin, Verstreken, Patrik, Cassiman, David, Vermeersch, Pieter, Verfaillie, Catherine, Hiller, Karsten, and Fendt, Sarah-Maria

Published
2016

17. Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa

Author

Gerits, Evelien, primary, Blommaert, Eline, additional, Lippell, Anna, additional, O’Neill, Alex J., additional, Weytjens, Bram, additional, De Maeyer, Dries, additional, Fierro, Ana Carolina, additional, Marchal, Kathleen, additional, Marchand, Arnaud, additional, Chaltin, Patrick, additional, Spincemaille, Pieter, additional, De Brucker, Katrijn, additional, Thevissen, Karin, additional, Cammue, Bruno P. A., additional, Swings, Toon, additional, Liebens, Veerle, additional, Fauvart, Maarten, additional, Verstraeten, Natalie, additional, and Michiels, Jan, additional

Published
2016
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18. Synergistic Activity of the Plant Defensin HsAFP1 and Caspofungin against Candida albicans Biofilms and Planktonic Cultures

Author

Vriens, Kim, primary, Cools, Tanne L., additional, Harvey, Peta J., additional, Craik, David J., additional, Spincemaille, Pieter, additional, Cassiman, David, additional, Braem, Annabel, additional, Vleugels, Jozef, additional, Nibbering, Peter H., additional, Drijfhout, Jan Wouter, additional, De Coninck, Barbara, additional, Cammue, Bruno P. A., additional, and Thevissen, Karin, additional

Published
2015
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19. The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease.

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Spincemaille, Pieter, Pham, Duc-Hung, Chandhok, Gursimran, Verbeek, Jef, Zibert, Andree, Libbrecht, Louis, Schmidt, Hartmut, Esguerra, Camila V, de Witte, Peter A M, Cammue, Bruno P A, Cassiman, David, Thevissen, Karin, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Spincemaille, Pieter, Pham, Duc-Hung, Chandhok, Gursimran, Verbeek, Jef, Zibert, Andree, Libbrecht, Louis, Schmidt, Hartmut, Esguerra, Camila V, de Witte, Peter A M, Cammue, Bruno P A, Cassiman, David, and Thevissen, Karin

Abstract

BACKGROUND: Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu-induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD. METHODS: The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu-treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae. RESULTS: OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B(H1069Q), but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species. CONCLUSIONS: OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD. GENERAL SIGNIFICANCE: All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment.

Published
2014

21. The Plant Decapeptide OSIP108 Can Alleviate Mitochondrial Dysfunction Induced by Cisplatin in Human Cells

Author

Spincemaille, Pieter, primary, Alborzinia, Hamed, additional, Dekervel, Jeroen, additional, Windmolders, Petra, additional, van Pelt, Jos, additional, Cassiman, David, additional, Cheneval, Olivier, additional, Craik, David, additional, Schur, Julia, additional, Ott, Ingo, additional, Wölfl, Stefan, additional, Cammue, Bruno, additional, and Thevissen, Karin, additional

Published
2014
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22. Roux-en-y gastric bypass attenuates hepatic mitochondrial dysfunction in mice with non-alcoholic steatohepatitis

Author

Verbeek, Jef, primary, Lannoo, Matthias, additional, Pirinen, Eija, additional, Ryu, Dongryeol, additional, Spincemaille, Pieter, additional, Vander Elst, Ingrid, additional, Windmolders, Petra, additional, Thevissen, Karin, additional, Cammue, Bruno P A, additional, van Pelt, Jos, additional, Fransis, Sabine, additional, Van Eyken, Peter, additional, Ceuterick-De Groote, Chantal, additional, Van Veldhoven, Paul P, additional, Bedossa, Pierre, additional, Nevens, Frederik, additional, Auwerx, Johan, additional, and Cassiman, David, additional

Published
2014
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24. Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin.

Author

Spincemaille P, Chandhok G, Zibert A, Schmidt H, Verbeek J, Chaltin P, Cammue BP, Cassiman D, and Thevissen K

Abstract

The human pathology Wilson disease (WD) is characterized by toxic copper (Cu) accumulation in brain and liver, resulting in, among other indications, mitochondrial dysfunction and apoptosis of hepatocytes. In an effort to identify novel compounds that can alleviate Cu-induced toxicity, we screened the Pharmakon 1600 repositioning library using a Cu-toxicity yeast screen. We identified 2 members of the drug class of Angiotensin II Type 1 receptor blockers (ARBs) that could increase yeast tolerance to Cu, namely Candesartan and Losartan. Subsequently, we show that specific ARBs can increase yeast tolerance to Cu and/or the chemotherapeutic agent cisplatin (Cp). The latter also induces mitochondrial dysfunction and apoptosis in mammalian cells. We further demonstrate that specific ARBs can prevent the prevalence of Cu-induced apoptotic markers in yeast, with Candesartan Cilexetil being the ARB which demonstrated most pronounced reduction of apoptosis-related markers. Next, we tested the sensitivity of a selection of yeast knockout mutants affected in detoxification of reactive oxygen species (ROS) and Cu for Candesartan Cilexetil rescue in presence of Cu. These data indicate that Candesartan Cilexetil increases yeast tolerance to Cu irrespectively of major ROS-detoxifying proteins. Finally, we show that specific ARBs can increase mammalian cell tolerance to Cu, as well as decrease the prevalence of Cu-induced apoptotic markers. All the above point to the potential of ARBs in preventing Cu-induced toxicity in yeast and mammalian cells., Competing Interests: Conflict of interest: The authors declare no conflict of interest.

Published
2014
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25. Sphingolipids and mitochondrial function, lessons learned from yeast.

Author

Spincemaille P, Cammue BP, and Thevissen K

Abstract

Mitochondrial dysfunction is a hallmark of several neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, but also of cancer, diabetes and rare diseases such as Wilson's disease (WD) and Niemann Pick type C1 (NPC). Mitochondrial dysfunction underlying human pathologies has often been associated with an aberrant cellular sphingolipid metabolism. Sphingolipids (SLs) are important membrane constituents that also act as signaling molecules. The yeast Saccharomyces cerevisiae has been pivotal in unraveling mammalian SL metabolism, mainly due to the high degree of conservation of SL metabolic pathways. In this review we will first provide a brief overview of the major differences in SL metabolism between yeast and mammalian cells and the use of SL biosynthetic inhibitors to elucidate the contribution of specific parts of the SL metabolic pathway in response to for instance stress. Next, we will discuss recent findings in yeast SL research concerning a crucial signaling role for SLs in orchestrating mitochondrial function, and translate these findings to relevant disease settings such as WD and NPC. In summary, recent research shows that S. cerevisiae is an invaluable model to investigate SLs as signaling molecules in modulating mitochondrial function, but can also be used as a tool to further enhance our current knowledge on SLs and mitochondria in mammalian cells., Competing Interests: Conflict of interest: The authors declare no conflict of interest.

Published
2014
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