Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy
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 Ca2+ homeostasis...
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ftuglasgow:oai:eprints.gla.ac.uk:149299 2023-05-15T18:41:14+02:00 Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy Mallo, Natalia Lamas, Jesús DeFelipe, Ana-Paula Sueiro, Rosa-Ana Fontenla, Francisco Leiro, José-Manuel 2016-07 http://eprints.gla.ac.uk/149299/ unknown Wiley Mallo, N. <http://eprints.gla.ac.uk/view/author/36521.html>, Lamas, J., DeFelipe, A.-P., Sueiro, R.-A., Fontenla, F. and Leiro, J.-M. (2016) Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy. Journal of Eukaryotic Microbiology <http://eprints.gla.ac.uk/view/journal_volume/Journal_of_Eukaryotic_Microbiology.html>, 63(4), pp. 505-515. (doi:10.1111/jeu.12294 <http://dx.doi.org/10.1111/jeu.12294>) (PMID:26751587) Articles PeerReviewed 2016 ftuglasgow https://doi.org/10.1111/jeu.12294 2020-01-10T01:30:01Z 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 Ca2+ 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 Ca2+ induced by ATP, indicating an effect on the Ca2+-ATPase. The results suggest that CQ and ART deregulate enzymes associated with PPi and Ca2+ metabolism, altering the intracellular pH homeostasis vital for parasite survival and providing a target for the development of new drugs against scuticociliatosis. Article in Journal/Newspaper Turbot University of Glasgow: Enlighten - Publications Journal of Eukaryotic Microbiology 63 4 505 515 |
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University of Glasgow: Enlighten - Publications |
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description |
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 Ca2+ 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 Ca2+ induced by ATP, indicating an effect on the Ca2+-ATPase. The results suggest that CQ and ART deregulate enzymes associated with PPi and Ca2+ metabolism, altering the intracellular pH homeostasis vital for parasite survival and providing a target for the development of new drugs against scuticociliatosis. |
format |
Article in Journal/Newspaper |
author |
Mallo, Natalia Lamas, Jesús DeFelipe, Ana-Paula Sueiro, Rosa-Ana Fontenla, Francisco Leiro, José-Manuel |
spellingShingle |
Mallo, Natalia Lamas, Jesús DeFelipe, Ana-Paula Sueiro, Rosa-Ana Fontenla, Francisco Leiro, José-Manuel Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy |
author_facet |
Mallo, Natalia Lamas, Jesús DeFelipe, Ana-Paula Sueiro, Rosa-Ana Fontenla, Francisco Leiro, José-Manuel |
author_sort |
Mallo, 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 |
publishDate |
2016 |
url |
http://eprints.gla.ac.uk/149299/ |
genre |
Turbot |
genre_facet |
Turbot |
op_relation |
Mallo, N. <http://eprints.gla.ac.uk/view/author/36521.html>, Lamas, J., DeFelipe, A.-P., Sueiro, R.-A., Fontenla, F. and Leiro, J.-M. (2016) Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy. Journal of Eukaryotic Microbiology <http://eprints.gla.ac.uk/view/journal_volume/Journal_of_Eukaryotic_Microbiology.html>, 63(4), pp. 505-515. (doi:10.1111/jeu.12294 <http://dx.doi.org/10.1111/jeu.12294>) (PMID:26751587) |
op_doi |
https://doi.org/10.1111/jeu.12294 |
container_title |
Journal of Eukaryotic Microbiology |
container_volume |
63 |
container_issue |
4 |
container_start_page |
505 |
op_container_end_page |
515 |
_version_ |
1766230726995345408 |