Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy
This is the peer reviewed version of the following article: Mallo, N., Lamas, J., DeFelipe, A.P., Sueiro, R.A., Fontenla, F. and Leiro JM. (2016), Enzymes Involved in Pyrophosphate and Calcium Metabolism as Targets for Antiscuticociliate Chemotherapy. J Eukaryot Microbiol 63(4): 505-15. doi:10.1111/...
Published in: | Journal of Eukaryotic Microbiology |
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Language: | English |
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Wiley
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Online Access: | http://hdl.handle.net/10347/18169 https://doi.org/10.1111/jeu.12294 |
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Philasterides dicentrarchi Inorganic pyrophosphatases Chloroquine Artemisinin Calcium Intracellular pH |
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Philasterides dicentrarchi Inorganic pyrophosphatases Chloroquine Artemisinin Calcium Intracellular pH Mallo Seijas, Natalia Lamas Fernández, Jesús Felipe González, Ana Paula de Sueiro Benavides, Rosa Ana Fontenla Iglesias, Francisco Leiro Vidal, José Manuel Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy |
topic_facet |
Philasterides dicentrarchi Inorganic pyrophosphatases Chloroquine Artemisinin Calcium Intracellular pH |
description |
This is the peer reviewed version of the following article: Mallo, N., Lamas, J., DeFelipe, A.P., Sueiro, R.A., Fontenla, F. and Leiro JM. (2016), Enzymes Involved in Pyrophosphate and Calcium Metabolism as Targets for Antiscuticociliate Chemotherapy. J Eukaryot Microbiol 63(4): 505-15. doi:10.1111/jeu.12294, which has been published in final form at https://doi.org/10.1111/jeu.12294. This article may be used for noncommercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions Inorganic pyrophosphate (PPi) is a key metabolite in cellular bioenergetics under chronic stress conditions in prokaryotes, protists and plants. Inorganic pyrophosphatases (PPases) are essential enzymes controlling the cellular concentration of PPi and mediating intracellular pH and Ca(2+) homeostasis. We report the effects of the antimalarial drugs chloroquine (CQ) and artemisinin (ART) on the in vitro growth of Philasterides dicentrarchi, a scuticociliate parasite of turbot; we also evaluated the action of these drugs on soluble (sPPases) and vacuolar H+-PPases (H+-PPases). CQ and ART inhibited the in vitro growth of ciliates with IC50 values of respectively 74 ± 9 μM and 80 ± 8 μM. CQ inhibits the H+ translocation (with an IC50 of 13.4 ± 0.2 μM), while ART increased translocation of H+ and acidification. However, both drugs caused a decrease in gene expression of H+-PPases. CQ significantly inhibited the enzymatic activity of sPPases, decreasing the consumption of intracellular PPi. ART inhibited intracellular accumulation of Ca(2+) induced by ATP, indicating an effect on the Ca(2+) -ATPase. The results suggest that CQ and ART deregulate enzymes associated with PPi and Ca(2+) metabolism, altering the intracellular pH homeostasis vital for parasite survival and providing a target for the development of new drugs against scuticociliatosis This study was financially supported by grant AGL2014-57125-R from the Ministerio de Economía y Competitividad (Spain), by the European Commission, under the ... |
author2 |
Universidade de Santiago de Compostela. Departamento de Bioloxía Funcional Universidade de Santiago de Compostela. Departamento de Microbioloxía e Parasitoloxía Universidade de Santiago de Compostela. Instituto de Acuicultura Universidade de Santiago de Compostela. Instituto de Investigación e Análises Alimentarias |
format |
Article in Journal/Newspaper |
author |
Mallo Seijas, Natalia Lamas Fernández, Jesús Felipe González, Ana Paula de Sueiro Benavides, Rosa Ana Fontenla Iglesias, Francisco Leiro Vidal, José Manuel |
author_facet |
Mallo Seijas, Natalia Lamas Fernández, Jesús Felipe González, Ana Paula de Sueiro Benavides, Rosa Ana Fontenla Iglesias, Francisco Leiro Vidal, José Manuel |
author_sort |
Mallo Seijas, Natalia |
title |
Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy |
title_short |
Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy |
title_full |
Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy |
title_fullStr |
Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy |
title_full_unstemmed |
Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy |
title_sort |
enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy |
publisher |
Wiley |
url |
http://hdl.handle.net/10347/18169 https://doi.org/10.1111/jeu.12294 |
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ENVELOPE(-56.933,-56.933,-64.333,-64.333) ENVELOPE(14.373,14.373,67.395,67.395) |
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Lamas Leiro |
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Lamas Leiro |
genre |
Turbot |
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Turbot |
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https://doi.org/10.1111/jeu.12294 info:eu-repo/grantAgreement/EC/H2020/634429 info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/AGL2014-57125-R/ES/DISEÑO Y ELABORACION DE NUEVAS VACUNAS QUE PERMITAN UNA MAYOR PROTECCION E INOCUIDAD FRENTE A ESCUTICOCILIADOS PARASITOS DEL RODABALLO Mallo, N., Lamas, J., DeFelipe, A.P., Sueiro, R.A., Fontenla, F. and Leiro JM. (2016), Enzymes Involved in Pyrophosphate and Calcium Metabolism as Targets for Anti-scuticociliate Chemotherapy. J Eukaryot Microbiol 63(4): 505-15. doi:10.1111/jeu.12294 http://hdl.handle.net/10347/18169 doi:10.1111/jeu.12294 1550-7408 |
op_rights |
© 2016 The Author(s) Journal of Eukaryotic Microbiology © 2016 International Society of Protistologists. This article may be used for noncommercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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https://doi.org/10.1111/jeu.12294 |
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Journal of Eukaryotic Microbiology |
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63 |
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4 |
container_start_page |
505 |
op_container_end_page |
515 |
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1772820630980263936 |
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ftunivsantcomp:oai:minerva.usc.es:10347/18169 2023-07-30T04:07:22+02:00 Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy Mallo Seijas, Natalia Lamas Fernández, Jesús Felipe González, Ana Paula de Sueiro Benavides, Rosa Ana Fontenla Iglesias, Francisco Leiro Vidal, José Manuel Universidade de Santiago de Compostela. Departamento de Bioloxía Funcional Universidade de Santiago de Compostela. Departamento de Microbioloxía e Parasitoloxía Universidade de Santiago de Compostela. Instituto de Acuicultura Universidade de Santiago de Compostela. Instituto de Investigación e Análises Alimentarias application/pdf http://hdl.handle.net/10347/18169 https://doi.org/10.1111/jeu.12294 eng eng Wiley https://doi.org/10.1111/jeu.12294 info:eu-repo/grantAgreement/EC/H2020/634429 info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/AGL2014-57125-R/ES/DISEÑO Y ELABORACION DE NUEVAS VACUNAS QUE PERMITAN UNA MAYOR PROTECCION E INOCUIDAD FRENTE A ESCUTICOCILIADOS PARASITOS DEL RODABALLO Mallo, N., Lamas, J., DeFelipe, A.P., Sueiro, R.A., Fontenla, F. and Leiro JM. (2016), Enzymes Involved in Pyrophosphate and Calcium Metabolism as Targets for Anti-scuticociliate Chemotherapy. J Eukaryot Microbiol 63(4): 505-15. doi:10.1111/jeu.12294 http://hdl.handle.net/10347/18169 doi:10.1111/jeu.12294 1550-7408 © 2016 The Author(s) Journal of Eukaryotic Microbiology © 2016 International Society of Protistologists. This article may be used for noncommercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Philasterides dicentrarchi Inorganic pyrophosphatases Chloroquine Artemisinin Calcium Intracellular pH info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion ftunivsantcomp https://doi.org/10.1111/jeu.12294 2023-07-11T23:26:07Z This is the peer reviewed version of the following article: Mallo, N., Lamas, J., DeFelipe, A.P., Sueiro, R.A., Fontenla, F. and Leiro JM. (2016), Enzymes Involved in Pyrophosphate and Calcium Metabolism as Targets for Antiscuticociliate Chemotherapy. J Eukaryot Microbiol 63(4): 505-15. doi:10.1111/jeu.12294, which has been published in final form at https://doi.org/10.1111/jeu.12294. This article may be used for noncommercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions Inorganic pyrophosphate (PPi) is a key metabolite in cellular bioenergetics under chronic stress conditions in prokaryotes, protists and plants. Inorganic pyrophosphatases (PPases) are essential enzymes controlling the cellular concentration of PPi and mediating intracellular pH and Ca(2+) homeostasis. We report the effects of the antimalarial drugs chloroquine (CQ) and artemisinin (ART) on the in vitro growth of Philasterides dicentrarchi, a scuticociliate parasite of turbot; we also evaluated the action of these drugs on soluble (sPPases) and vacuolar H+-PPases (H+-PPases). CQ and ART inhibited the in vitro growth of ciliates with IC50 values of respectively 74 ± 9 μM and 80 ± 8 μM. CQ inhibits the H+ translocation (with an IC50 of 13.4 ± 0.2 μM), while ART increased translocation of H+ and acidification. However, both drugs caused a decrease in gene expression of H+-PPases. CQ significantly inhibited the enzymatic activity of sPPases, decreasing the consumption of intracellular PPi. ART inhibited intracellular accumulation of Ca(2+) induced by ATP, indicating an effect on the Ca(2+) -ATPase. The results suggest that CQ and ART deregulate enzymes associated with PPi and Ca(2+) metabolism, altering the intracellular pH homeostasis vital for parasite survival and providing a target for the development of new drugs against scuticociliatosis This study was financially supported by grant AGL2014-57125-R from the Ministerio de Economía y Competitividad (Spain), by the European Commission, under the ... Article in Journal/Newspaper Turbot Minerva - Repositorio institucional da Universidade de Santiago de Compostela (USC) Lamas ENVELOPE(-56.933,-56.933,-64.333,-64.333) Leiro ENVELOPE(14.373,14.373,67.395,67.395) Journal of Eukaryotic Microbiology 63 4 505 515 |