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3. Oxidation of clofibric acid in aqueous solution using a non-thermal plasma discharge or gamma radiation

Author

Madureira, Joana, Ceriani, Elisa, Pinhão, Nuno, Marotta, Ester, Melo, Rita, Verde, Sandra Cabo, Paradisi, Cristina, and Margaça, Fernanda M. A.

Subjects
Physics - Chemical Physics, Physics - Applied Physics, Physics - Biological Physics
Abstract

In this work, we study degradation of clofibric acid (CFA) in aqueous solution using either ionizing radiation from a $^{60}$Co source or a non-thermal plasma produced by discharges in the air above the solution. The results obtained with the two technologies are compared in terms of effectiveness of CFA degradation and its by-products. In both cases the CFA degradation follows a quasi-exponential decay in time well modelled by a kinetic scheme which considers the competition between CFA and all reaction intermediates for the reactive species generated in solution as well as the amount of the end product formed. A new degradation law is deduced to explain the results. Although the end-product CO$_2$ was detected and the CFA conversion found to be very high under the studied conditions, HPLC analysis reveals several degradation intermediates still bearing the aromatic ring with the chlorine substituent. The extent of mineralization is rather limited. The energy yield is found to be higher in the gamma radiation experiments., Comment: 25 pages, 7 figures

Published
2017
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5. Pharmacological modulation of Kv1.3 potassium channel selectively triggers pathological B lymphocyte apoptosis in vivo in a genetic CLL model

Author

Severin, Filippo, Urbani, Andrea, Varanita, Tatiana, Bachmann, Magdalena, Azzolini, Michele, Martini, Veronica, Pizzi, Marco, Tos, Angelo Paolo Dei, Frezzato, Federica, Mattarei, Andrea, Ghia, Paolo, Bertilaccio, Maria Teresa Sabrina, Gulbins, Erich, Paradisi, Cristina, Zoratti, Mario, Semenzato, Gianpietro Carlo, Leanza, Luigi, Trentin, Livio, and Szabò, Ildiko

Published
2022
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6. Insight into the mechanism of cytotoxicity of membrane-permeant psoralenic Kv1.3 channel inhibitors by chemical dissection of a novel member of the family

Author

Peruzzo, Roberta, Mattarei, Andrea, Azzolini, Michele, Becker-Flegler, Katrin Anne, Romio, Matteo, Rigoni, Giovanni, Carrer, Andrea, Biasutto, Lucia, Parrasia, Sofia, Kadow, Stephanie, Managò, Antonella, Urbani, Andrea, Rossa, Andrea, Semenzato, Gianpietro, Soriano, Maria Eugenia, Trentin, Livio, Ahmad, Syed, Edwards, Michael, Gulbins, Erich, Paradisi, Cristina, Zoratti, Mario, Leanza, Luigi, and Szabò, Ildikò

Published
2020
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9. Air non-thermal plasma, a green approach for the treatment of contaminated water: the case of sulfamethoxazole.

Author

Giardina, Agata, Lofrano, Giusy, Libralato, Giovanni, Siciliano, Antonietta, Marotta, Ester, and Paradisi, Cristina

Subjects
NON-thermal plasmas, WATER pollution, WATER purification, PERSISTENT pollutants, SULFAMETHOXAZOLE, MASS burials
Abstract

Non-thermal plasma (NTP) is gaining increasing attention as a promising approach for advanced water treatment to degrade persistent organic pollutants. Aqueous solutions of sulfamethoxazole (4-amino-N-(5-methylisoxazol-3-yl)-benzensulfonamide, SMZ), an antibiotic largely employed for humans and animals and a widespread persistent pollutant of waters and wastewaters, were subjected to air NTP treatment in a dielectric barrier discharge (DBD) reactor. The effects of SMZ initial concentration and of the solution pH on SMZ decomposition kinetics and transformation products were investigated. Efficient degradation was achieved, resulting in the complete removal of SMZ (10 µM initial concentration) in less than 25 min treatments, in the exhaustive mineralization (a result never reported before in plasma treatments and seldom reached also with other advanced oxidation processes) of all organic carbon in 6 h and in an energy efficiency of 6.4 g/kWh at 50% conversion. By means of HPLC-UV/Vis and LC-ESI-MSn analyses, a number of organic transformation products was identified along the path to SMZ mineralization, all present always in very small amounts and in turn decomposed at short treatment times. The effect of the solution pH on the genesis and decay of transformation products was also investigated. Based on comparisons with literature data and on previous findings obtained with the DBD reactor used in this work, it is concluded that the major reactive species involved in the degradation of SMZ are the hydroxyl radical and ozone. Finally, toxicological analyses of water initially containing 0.5 mMSMZ and subjected to 4 h NTP treatment showed that the by-products are not toxic to Raphidocelis subcapitata and Daphnia magna, while residual toxicity was detected by Aliivibrio fischeri. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Direct Pharmacological Targeting of a Mitochondrial Ion Channel Selectively Kills Tumor Cells In Vivo

Author

Leanza, Luigi, Romio, Matteo, Becker, Katrin Anne, Azzolini, Michele, Trentin, Livio, Managò, Antonella, Venturini, Elisa, Zaccagnino, Angela, Mattarei, Andrea, Carraretto, Luca, Urbani, Andrea, Kadow, Stephanie, Biasutto, Lucia, Martini, Veronica, Severin, Filippo, Peruzzo, Roberta, Trimarco, Valentina, Egberts, Jan-Hendrik, Hauser, Charlotte, Visentin, Andrea, Semenzato, Gianpietro, Kalthoff, Holger, Zoratti, Mario, Gulbins, Erich, Paradisi, Cristina, and Szabo, Ildiko

Published
2017
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13. Dispersity within brushes plays a major role in determining their interfacial properties : the case of oligoxazoline-based graft polymers

Author

Romio, Matteo, Grob, Benjamin, Trachsel, Lucca, Mattarei, Andrea, Morgese, Giulia, Ramakrishna, Shivaprakash N., Niccolai, Francesca, Guazzelli, Elisa, Paradisi, Cristina, Martinelli, Elisa, Spencer, Nicholas D., Benetti, Edmondo M., Romio, Matteo, Grob, Benjamin, Trachsel, Lucca, Mattarei, Andrea, Morgese, Giulia, Ramakrishna, Shivaprakash N., Niccolai, Francesca, Guazzelli, Elisa, Paradisi, Cristina, Martinelli, Elisa, Spencer, Nicholas D., and Benetti, Edmondo M.

Abstract

Many synthetic polymers used to form polymer-brush films feature a main backbone with functional, oligomeric side chains. While the structure of such graft polymers mimics biomacromolecules to an extent, it lacks the monodispersity and structural purity present in nature. Here we demonstrate that side-chain heterogeneity within graft polymers significantly influences hydration and the occurrence of hydrophobic interactions in the subsequently formed brushes and consequently impacts fundamental interfacial properties. This is demonstrated for the case of poly(methacrylate)s (PMAs) presenting oligomeric side chains of different length (n) and dispersity. A precise tuning of brush structure was achieved by first synthesizing oligo(2-ethyl-2-oxazoline) methacrylates (OEOXMAs) by cationic ring-opening polymerization (CROP), subsequently purifying them into discrete macromonomers with distinct values of n by column chromatography, and finally obtaining poly[oligo(2-ethyl-2-oxazoline) methacrylate]s (POEOXMAs) by reversible addition-fragmentation chain-transfer (RAFT) polymerization. Assembly of POEOXMA on Au surfaces yielded graft polymer brushes with different side-chain dispersities and lengths, whose properties were thoroughly investigated by a combination of variable angle spectroscopic ellipsometry (VASE), quartz crystal microbalance with dissipation (QCMD), and atomic force microscopy (AFM) methods. Side-chain dispersity, or dispersity within brushes, leads to assemblies that are more hydrated, less adhesive, and more lubricious and biopassive compared to analogous films obtained from graft polymers characterized by a homogeneous structure.

Published
2023

18. Inhibition of a Mitochondrial Potassium Channel in Combination with Gemcitabine and Abraxane Drastically Reduces Pancreatic Ductal Adenocarcinoma in an Immunocompetent Orthotopic Murine Model

Author

Li, Weiwei, primary, Wilson, Gregory C., additional, Bachmann, Magdalena, additional, Wang, Jiang, additional, Mattarei, Andrea, additional, Paradisi, Cristina, additional, Edwards, Michael J., additional, Szabo, Ildiko, additional, Gulbins, Erich, additional, Ahmad, Syed A., additional, and Patel, Sameer H., additional

Published
2022
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19. Additional file 1 of Pharmacological modulation of Kv1.3 potassium channel selectively triggers pathological B lymphocyte apoptosis in vivo in a genetic CLL model

Author

Severin, Filippo, Urbani, Andrea, Varanita, Tatiana, Bachmann, Magdalena, Azzolini, Michele, Martini, Veronica, Pizzi, Marco, Tos, Angelo Paolo Dei, Frezzato, Federica, Mattarei, Andrea, Ghia, Paolo, Bertilaccio, Maria Teresa Sabrina, Gulbins, Erich, Paradisi, Cristina, Zoratti, Mario, Semenzato, Gianpietro Carlo, Leanza, Luigi, Trentin, Livio, and Szab��, Ildiko

Abstract

Additional file 1: Supplementary Figure 1. Kaplan-Meier Estimates. of the probability of developing disease during the life span of E��-TCL1 mice. Supplementary Figure 2. Flow cytometric panels showing the gating strategy. Supplementary Figure 3. Histological features of spleens from E��-TCL1 mice with no splenomegaly. Supplementary Figure 4. Residual CLL cells from PAPTP-treated E��-TCL1 mice respond to PAPTP treatment in ex vivo setting. Supplementary Figure 5. Expression of KCa3.1 channel in mitochondria of human B-CLL cells and effect of TRAM-34 on death. Supplementary Figure 6. Effect of TRAM-34 on proliferation and survival of B-CLL cells from E��-TCL1 mice. Supplementary Figure 7. PAPTP does not induce ROS release and mitochondrial depolarization in B lymphocytes of healthy subjects.

Published
2022
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22. Corrigendum to “Insight into the mechanism of cytotoxicity of membrane-permeant psoralenic Kv1.3 channel inhibitors by chemical dissection of a novel member of the family” [Redox Biol. 37 (2020 Sep 6) 101705–101721]

Author

Peruzzo, Roberta, Mattarei, Andrea, Azzolini, Michele, Becker-Flegler, Katrin Anne, Romio, Matteo, Rigoni, Giovanni, Carrer, Andrea, Biasutto, Lucia, Parrasia, Sofia, Kadow, Stephanie, Managò, Antonella, Urbani, Andrea, Rossa, Andrea, Semenzato, Gianpietro, Soriano, Maria Eugenia, Trentin, Livio, Ahmad, Syed, Edwards, Michael, Gulbins, Erich, Paradisi, Cristina, Zoratti, Mario, Leanza, Luigi, and Szabò, Ildikò

Published
2021
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24. Corrigendum to: 'Insight into the mechanism of cytotoxicity of membrane-permeant psoralenic Kv1.3 channel inhibitors by chemical dissection of a novel member of the family'

Author

Peruzzo, Roberta, Mattarei, Andrea, Azzolini, Michele, Becker-Flegler, Katrin Anne, Romio, Matteo, Rigoni, Giovanni, Carrer, Andrea, Biasutto, Lucia, Parrasia, Sofia, Kadow, Stephanie, Managò, Antonella, Urbani, Andrea, Rossa, Andrea, Semenzato, Gianpietro, Soriano, Maria Eugenia, Trentin, Livio, Ahmad, Syed, Edwards, Michael, Gulbins, Erich, Paradisi, Cristina, Zoratti, Mario, Leanza, Luigi, and Szabò, Ildikò

Subjects
Biologie
Abstract

The authors regret that the references appear with the numbers in the text, while they are listed in alphabetical order in the References section. The correct reference list is the following: References [1] G.A. Gutman, K.G. Chandy, S. Grissmer, M. Lazdunski, D. McKinnon, L.A. Pardo, G.A. Robertson, B. Rudy, M.C. Sanguinetti, W. Stuhmer, X. Wang, International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels, Pharmacological reviews, 57 (2005) 473-508. [2] A. Serrano-Albarras, I. Estadella, S. Cirera-Rocosa, M. Navarro-Perez, A. Felipe, Kv1.3: a multifunctional channel with many pathological implications, Expert opinion on therapeutic targets, 22 (2018) 101-105. [3] S. Feske, H. Wulff, E.Y. Skolnik, Ion channels in innate and adaptive immunity, Annual review of immunology, 33 (2015) 291-353. [4] G. Panyi, C. Beeton, A. Felipe, Ion channels and anti-cancer immunity, Philosophical transactions of the Royal Society of London. 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Published
2021

25. Application of fluorescence-based probes for the determination of superoxide in water treated with air non-thermal plasma

Author

Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits, Cabrellon, Gabriele, Tampieri, Francesco, Rossa, Andrea, Barbon, Antonio, Marotta, Ester, Paradisi, Cristina, Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits, Cabrellon, Gabriele, Tampieri, Francesco, Rossa, Andrea, Barbon, Antonio, Marotta, Ester, and Paradisi, Cristina

Abstract

Superoxide is one of the reactive oxygen species (ROS) in non-thermal plasmas generated by electrical discharges in air at room temperature and atmospheric pressure. One important application of such plasmas is the activation of advanced oxidation processes for air and water decontaminating treatments. When in contact with aqueous media, ROS and notably superoxide can react at the plasma/liquid interface or transfer and react into the liquid. While the detection of superoxide in plasma-treated water has been reported in the literature, to the best of our knowledge, quantitative determinations are lacking. We report here the determination of superoxide rate of formation and steady-state concentration in water subjected to air non-thermal plasma in a streamer discharge reactor used previously to treat various organic contaminants. After detecting the presence of superoxide by spin-trapping and electron paramagnetic resonance analyses, we applied superoxide-selective fluorescent probes to carry out quantitative determinations. The first probe tested, 3',6'-bis(diphenylphosphinyl) fluorescein (PF-1), was not sufficiently soluble, but the second one, fluorescein-bis-[(N-methylpyridinium-3-yl)sulfonate iodide] (FMSI), was applied successfully. Under typical plasma operating conditions, the rate of superoxide formation and its steady-state concentration were (0.27 ± 0.15) µM s–1 and (0.007 ± 0.004) nM, respectively. The procedure outlined here can be usefully applied to detect and quantify superoxide in water treated by different plasma sources in various types of plasma reactors., Peer Reviewed, Postprint (author's final draft)

Published
2020

28. Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

Author

Costa, Roberto, Peruzzo, Roberta, Bachmann, Magdalena, Montà, Giulia Dalla, Vicario, Mattia, Santinon, Giulia, Mattarei, Andrea, Moro, Enrico, Quintana-Cabrera, Rubén, Scorrano, Luca, Zeviani, Massimo, Vallese, Francesca, Zoratti, Mario, Paradisi, Cristina, Argenton, Francesco, Brini, Marisa, Calì, Tito, Dupont, Sirio, Szabò, Ildikò, and Leanza, Luigi

Published
2019
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29. Pathways of nitrosobenzene reduction by thiols in alcoholic media

Author

Montanari, Stefano, Paradisi, Cristina, and Scorrano, Gianfranco

Subjects
Nitrobenzenes -- Research, Reactivity (Chemistry) -- Research, Thiols -- Research, Biological sciences, Chemistry
Abstract

Research was conducted to examine the biologically important reaction of nitrosobenzenes with thiols in 2-propanol solution at room temperature. The mechanistic investigation of the reaction was based mainly on in situ 1H NMR analysis. Results highlight the crucial role played by the solvent on the reactivity in the complex systems. Findings also demonstrate that the reaction of the adduct does not require free benzenethiol.

Published
1999

30. Kinetics and products of air plasma induced oxidation in water of imidacloprid and thiamethoxam treated individually and in mixture

Author

Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits, Tampieri, Francesco, Durighello, Alessandro, Biondo, Omar, Gasior, Marcelina, Knys, Aleksandra, Marotta, Ester, Paradisi, Cristina, Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits, Tampieri, Francesco, Durighello, Alessandro, Biondo, Omar, Gasior, Marcelina, Knys, Aleksandra, Marotta, Ester, and Paradisi, Cristina

Abstract

Imidacloprid (I) and thiamethoxam (T) are widely used neonicotinoid insecticides with high persistence in the environment and thus included in the watch list of substances for European Union-wide monitoring reported in the Decision 2015/495/EU. In this work aqueous solutions of I, T and I¿+¿T were subjected to advanced oxidation by air plasma produced by negative DC corona discharges above the liquid surface. The oxidative degradation of each pollutant was investigated by monitoring the rate and the products of its decay when treated alone and in the presence of variable amounts of the other compound. The results show that both I and T are readily degraded and that mineralization can be achieved in this process, as proven by the measurement of the residual organic carbon and by the quantitative conversion of chlorine and sulfur into inorganic chloride and sulfate, respectively. The major organic intermediates formed during the complex stepwise oxidation of I and T were identified and monitored by HPLC–MS/MS analysis. The results of kinetic studies show that both for I and T the reaction rate depends inversely on the insecticide initial concentration, that I and T have similar reactivities and that they do not interfere reciprocally in any specific way when treated in mixture at a total concentration of ca 1¿×¿10-4 M. Based on literature data and on previous results with the same reactor, it is reasonable to propose that the oxidation of I and T is initiated by the reaction with OH radicals., Peer Reviewed, Postprint (author's final draft)

Published
2019

31. Radicals and ions formed in plasma-treated organic solvents: a mechanistic investigation to rationalize the enhancement of electrospinnability of polycaprolactont

Author

Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits, Grande, Silvia, Tampieri, Francesco, Nikiforov, Anton, Giardina, Agata, Barbon, Antonio, Cools, Pieter, Morent, Rino, Paradisi, Cristina, Marotta, Ester, De Geyter, Nathalie, Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits, Grande, Silvia, Tampieri, Francesco, Nikiforov, Anton, Giardina, Agata, Barbon, Antonio, Cools, Pieter, Morent, Rino, Paradisi, Cristina, Marotta, Ester, and De Geyter, Nathalie

Abstract

This paper reports and discusses the beneficial effects on the quality of electrospun polycaprolactone nanofibers brought about by pretreatment of the solvent with non-thermal plasma. Chloroform/dimethylformamide 9:1 (CHCl3:DMF 9:1) and pure chloroform were pretreated by a few minute exposure to the plasma generated by an atmospheric pressure plasma jet (APPJ). Interestingly, when pure chloroform was used, the advantages of plasma pretreatment of the solvent were way less pronounced than found with the CHCl3:DMF 9:1 mixture. The chemical modifications induced by the plasma in the solvents were investigated by means of complementary analytical techniques. GC-MS revealed the formation of solvent-derived volatile products, notably tetrachloroethylene (C2Cl4), 1,1,2,2-tetrachloroethane (C2H2Cl4), pentachloroethane (C2HCl5), hexachloroethane (C2Cl6) and, in the case of the mixed solvent, also N-methylformamide (C2H5NO). The chlorinated volatile products are attributed to reactions of ·Cl and Cl-containing methyl radicals and carbenes formed in the plasma-treated solvents. ·Cl and ·CCl3 radicals were detected and identified by EPR spectroscopy analyses. Ion chromatography revealed the presence of Cl-, NO- 3 , and HCOO- (the latter only in the presence of DMF) in the plasma-treated solvents, thus accounting for the observed increased conductivity and acidification of the solvent after plasma treatment. Mechanisms for the formation of these solvent derived products induced by plasma are proposed and discussed. The major role of radicals and ions in the plasma chemistry of chloroform and of the chloroform/dimethylformamide mixture is highlighted. The results provide insight into the interaction of plasma with organic solvents, a field so far little explored but holding promise for interesting applications., Peer Reviewed, Postprint (published version)

Published
2019

32. Thil anions in nucleophilic aromatic substitution reactions with activated aryl halides: attack on carbon vs attack on halogen

Author

Montanari, Stefano, Paradisi, Cristina, and Scorrano, Gianfranco

Subjects
Thiols -- Analysis, Anions -- Analysis, Substitution reactions -- Analysis, Halides -- Analysis, Carbon -- Analysis, Halogens -- Analysis, Biological sciences, Chemistry
Abstract

The omicron-nitrophenyl thioether and nitrobenzene are generated in associated ratios when omicron-iodonitrobenzene interacts with thiol anions (RSNa) in 2-propanol solution. The products display a rate which relies on the characteristic of R in the thiol anions. A radical chain functioning reveals varying results of energetic studies and of the analysis of adding D. The same functioning is adopted to examine the hydro-de-halogenation of aryl halides, which is supported by alkoxide. The participation of an omicron-nitrophenyl anion in the form of a carbanionic intermediate is revealed. A sulfenyl halide and the omicron-nitrophenyl anion are produced when iodine is subjected to a nucleophilic addition.

Published
1993

33. Radicals and Ions Formed in Plasma-Treated Organic Solvents: A Mechanistic Investigation to Rationalize the Enhancement of Electrospinnability of Polycaprolactone

Author

Grande, Silvia, primary, Tampieri, Francesco, additional, Nikiforov, Anton, additional, Giardina, Agata, additional, Barbon, Antonio, additional, Cools, Pieter, additional, Morent, Rino, additional, Paradisi, Cristina, additional, Marotta, Ester, additional, and De Geyter, Nathalie, additional

Published
2019
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34. Characterization of a plasma source for biomedical applications by electrical, optical, and chemical measurements

Author

Neretti, G, Tampieri, F, Borghi, C, Brun, P, Cavazzana, R, Cordaro, L, Marotta, E, Paradisi, C, Seri, P, Taglioli, M, Zaniol, B, Zuin, M, Martines, E, Neretti, Gabriele, Tampieri, Francesco, Borghi, Carlo Angelo, Brun, Paola, Cavazzana, Roberto, Cordaro, Luigi, Marotta, Ester, Paradisi, Cristina, Seri, Paolo, Taglioli, Matteo, Zaniol, Barbara, Zuin, Matteo, Martines, Emilio, Neretti, G, Tampieri, F, Borghi, C, Brun, P, Cavazzana, R, Cordaro, L, Marotta, E, Paradisi, C, Seri, P, Taglioli, M, Zaniol, B, Zuin, M, Martines, E, Neretti, Gabriele, Tampieri, Francesco, Borghi, Carlo Angelo, Brun, Paola, Cavazzana, Roberto, Cordaro, Luigi, Marotta, Ester, Paradisi, Cristina, Seri, Paolo, Taglioli, Matteo, Zaniol, Barbara, Zuin, Matteo, and Martines, Emilio

Abstract

This paper reports the characterization of a low-power, atmospheric pressure plasma source developed for and successfully tested in applications of plasma medicine. The source produces plasma by ionizing a helium flow containing traces of air. The effluent gas is thus enriched in reactive oxygen and nitrogen species as well as helium metastable excited states. Electrical measurements, Schlieren imaging, OES and various chemical analyses and probes enabled us to fully characterize the plasma source and to determine some fundamental parameters for treating living samples such as the power feeding the discharge, the optimal source to target distance, the maximum exposure time, and to identify the major chemical species responsible for the biological action on exposed living matter.

Published
2018

35. Mitochondrial ATP production is required for Wnt signaling modulation

Author

Leanza, Luigi, primary, Costa, Roberto, additional, Peruzzo, Roberta, additional, Bachmann, Magdalena, additional, Santinon, Giulia, additional, Vicario, Mattia, additional, Montà, Giulia Dalla, additional, Mattarei, Andrea, additional, Cabrera, Ruben Quintana, additional, Moro, Enrico, additional, Scorrano, Luca, additional, Zeviani, Massimo, additional, Zoratti, Mario, additional, Paradisi, Cristina, additional, Argenton, Francesco, additional, Brini, Marisa, additional, Calì, Tito, additional, Dupont, Sirio, additional, and Szabò, Ildikò, additional

Published
2018
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38. Targeting the Potassium Channel Kv1.3 Kills Glioblastoma Cells

Author

Venturini, Elisa, Leanza, Luigi, Azzolini, Michele, Kadow, Stephanie, Mattarei, Andrea, Weller, Michael, Tabatabai, Ghazaleh, Edwards, Michael J, Zoratti, Mario, Paradisi, Cristina, Szabò, Ildikò, Gulbins, Erich, Becker, Katrin Anne, Venturini, Elisa, Leanza, Luigi, Azzolini, Michele, Kadow, Stephanie, Mattarei, Andrea, Weller, Michael, Tabatabai, Ghazaleh, Edwards, Michael J, Zoratti, Mario, Paradisi, Cristina, Szabò, Ildikò, Gulbins, Erich, and Becker, Katrin Anne

Published
2017

41. Targeting the Potassium Channel Kv1.3 Kills Glioblastoma Cells

Author

Venturini, Elisa, primary, Leanza, Luigi, additional, Azzolini, Michele, additional, Kadow, Stephanie, additional, Mattarei, Andrea, additional, Weller, Michael, additional, Tabatabai, Ghazaleh, additional, Edwards, Michael J., additional, Zoratti, Mario, additional, Paradisi, Cristina, additional, Szabò, Ildikò, additional, Gulbins, Erich, additional, and Becker, Katrin Anne, additional

Published
2017
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42. Inhibition of PI-3-K and AKT Amplifies Kv1.3 Inhibitor-Induced Death of Human T Leukemia Cells.

Author

Bergermann, Tim, Born, Lukas, Ferguson, Fiona, Latkovic, Paula, Scheul, Alexandra, Sonnenschein, Nina, Leanza, Luigi, Keitsch, Simone, Sehl, Carolin, Wilker, Barbara, Edwards, Michael J., Zoratti, Mario, Paradisi, Cristina, Kohnen, Markus, Szabo, Ildiko, Becker, Katrin Anne, and Carpinteiro, Alexander

Subjects
HUMAN T cells, HTLV, HYPERPOLARIZATION (Cytology), REACTIVE oxygen species, CELL death inhibition
Abstract

Background/Aims: We have previously shown that inhibition of the mitochondrial Kv1.3 channel results in an initial mitochondrial hyperpolarization and a release of oxygen radicals that mediate mitochondrial depolarization, cytochrome c release and death. Here, we investigated whether inhibition of Kv1.3 channels can also induce cellular resistance mechanisms that counteract the induction of cell death under certain conditions. Methods: We treated leukemic T cells with the mitochondria-targeted Kv1.3 inhibitor PCARBTP and determined the activity of different kinases associated with cell survival including ZAP70, PI-3-K, AKT, JNK and ERK by measuring the activation-associated phosphorylation of these proteins. Furthermore, we inhibited AKT and JNK and determined the effect of PCARBTP-induced tumor cell death. Results: We demonstrate that treatment of Jurkat T leukemia cells with low doses of the mitochondria-targeted inhibitor of Kv1.3 PCARBTP (0.25 µM or 1 µM) for 10 minutes induced a constitutive phosphorylation/activation of the pro-survival signaling molecules ZAP70, PI-3-K, AKT and JNK, while the phosphorylation/activation of ERK was not affected. Stimulation of Jurkat cells via the TCR/CD3 complex induced an additional activation of a similar pattern of signaling events. Higher doses of the Kv1.3 inhibitor, i.e. 10 µM PCARBTP, reduced the basal phosphorylation/activation of these signaling molecules and also impaired their activation upon stimulation via the TCR/CD3 complex. A low dose of PCARBTP, i.e. 0.25 µM PCARBTP, was almost without any effect on cell death. In contrast, concomitant inhibition of PI-3-K or AKT greatly sensitized Jurkat leukemia cells to the Kv1.3 inhibitor PCARBTP and allowed induction of cell death already at 0.25 µM PCARBTP. Conclusion: These studies indicate that Jurkat leukemia cells respond to low doses of the mitochondria-targeted Kv1.3 inhibitor PCARBTP with an activation of survival signals counteracting cell death. Inhibition of these T cell survival signals sensitizes leukemia cells to death induced by mitochondria-targeted Kv1.3 inhibitors. High doses of the Kv1.3 inhibitor inactivate these signals directly permitting death. [ABSTRACT FROM AUTHOR]

Published
2019
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45. Targeting the Potassium Channel Kv1.3 Kills Glioblastoma Cells.

Author

Venturini, Elisa, Leanza, Luigi, Azzolini, Michele, Kadow, Stephanie, Mattarei, Andrea, Weller, Michael, Tabatabai, Ghazaleh, Edwards, Michael J., Zoratti, Mario, Paradisi, Cristina, Szabò, Ildikò, Gulbins, Erich, and Becker, Katrin Anne

Subjects
GLIOMAS, BRAIN tumors
Abstract

Background/Aims: Glioblastoma (GBM) is one of the most aggressive cancers, counting for a high number of the newly diagnosed patients with central nervous system (CNS) cancers in the United States and Europe. Major features of GBM include aggressive and invasive growth as well as a high resistance to treatment. Kv1.3, a potassium channel of the shaker family, is expressed in the inner mitochondrial membrane of many cancer cells. Inhibition of mitochondrial Kv1.3 was shown to induce apoptosis in several tumor cells at doses that were not lethal for normal cells. Methods: We investigated the expression of Kv1.3 in different glioma cell lines by immunocytochemistry, western blotting and electron microscopy and analyzed the effect of newly synthesized, mitochondria-targeted, Kv1.3 inhibitors on the induction of cell death in these cells. Finally, we performed in vivo studies on glioma bearing mice. Results: Here, we report that Kv1.3 is expressed in mitochondria of human and murine GL261, A172 and LN308 glioma cells. Treatment with the novel Kv1.3 inhibitors PAPTP or PCARBTP as well as with clofazimine induced massive cell death in glioma cells, while Psora-4 and PAP-1 were almost without effect. However, in vivo experiments revealed that the drugs had no effect on orthotopic brain tumors in vivo. Conclusion: These data serve as proof of principle that Kv1.3 inhibitors kills GBM cells, but drugs that act in vivo against glioblastoma must be developed to translate these findings in vivo. [ABSTRACT FROM AUTHOR]

Published
2018
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46. A Novel Inhibitor Prevents the Peripheral Neuroparalysis of Botulinum Neurotoxins

Author

Azarnia Tehran, Domenico, primary, Zanetti, Giulia, additional, Leka, Oneda, additional, Lista, Florigio, additional, Fillo, Silvia, additional, Binz, Thomas, additional, Shone, Clifford C., additional, Rossetto, Ornella, additional, Montecucco, Cesare, additional, Paradisi, Cristina, additional, Mattarei, Andrea, additional, and Pirazzini, Marco, additional

Published
2015
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