Antimalarial drugs disrupt ion homeostasis in malarial parasites

Plasmodium chabaudi malaria parasite organelles are major elements for ion homeostasis and cellular signaling and also target for antimalarial drugs. By using confocal imaging of intraerythrocytic parasites we demonstrated that the dye acridine orange (AO) is accumulated into P. chabaudi subcellular...

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Main Authors: Marcos L Gazarini, Carlos AO Sigolo, Regina P Markus, Andrew P Thomas, Célia RS Garcia
Format: Article
Language:English
Published: Fundação Oswaldo Cruz (FIOCRUZ) 2007-06-01
Series:Memorias do Instituto Oswaldo Cruz
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300012
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author Marcos L Gazarini
Carlos AO Sigolo
Regina P Markus
Andrew P Thomas
Célia RS Garcia
author_facet Marcos L Gazarini
Carlos AO Sigolo
Regina P Markus
Andrew P Thomas
Célia RS Garcia
author_sort Marcos L Gazarini
collection DOAJ
description Plasmodium chabaudi malaria parasite organelles are major elements for ion homeostasis and cellular signaling and also target for antimalarial drugs. By using confocal imaging of intraerythrocytic parasites we demonstrated that the dye acridine orange (AO) is accumulated into P. chabaudi subcellular compartments. The AO could be released from the parasite organelles by collapsing the pH gradient with the K+/H+ ionophore nigericin (20 µM), or by inhibiting the H+-pump with bafilomycin (4 µM). Similarly, in isolated parasites loaded with calcium indicator Fluo 3-AM, bafilomycin caused calcium mobilization of the acidic calcium pool that could also be release with nigericin. Interestingly after complete release of the acidic compartments, addition of thapsigargin at 10 µM was still effective in releasing parasite intracellular calcium stores in parasites at trophozoite stage. The addition of antimalarial drugs chloroquine and artemisinin resulted in AO release from acidic compartments and also affected maintenance of calcium in ER store by using different drug concentrations.
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spelling doaj.art-7fad1867a27b44fe8f7bd71a01fca28f2023-09-02T16:25:25ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz0074-02761678-80602007-06-011023329334Antimalarial drugs disrupt ion homeostasis in malarial parasitesMarcos L GazariniCarlos AO SigoloRegina P MarkusAndrew P ThomasCélia RS GarciaPlasmodium chabaudi malaria parasite organelles are major elements for ion homeostasis and cellular signaling and also target for antimalarial drugs. By using confocal imaging of intraerythrocytic parasites we demonstrated that the dye acridine orange (AO) is accumulated into P. chabaudi subcellular compartments. The AO could be released from the parasite organelles by collapsing the pH gradient with the K+/H+ ionophore nigericin (20 µM), or by inhibiting the H+-pump with bafilomycin (4 µM). Similarly, in isolated parasites loaded with calcium indicator Fluo 3-AM, bafilomycin caused calcium mobilization of the acidic calcium pool that could also be release with nigericin. Interestingly after complete release of the acidic compartments, addition of thapsigargin at 10 µM was still effective in releasing parasite intracellular calcium stores in parasites at trophozoite stage. The addition of antimalarial drugs chloroquine and artemisinin resulted in AO release from acidic compartments and also affected maintenance of calcium in ER store by using different drug concentrations.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300012malariaPlasmodium chabaudicalciumchloroquineartemisininacidic compartment
spellingShingle Marcos L Gazarini
Carlos AO Sigolo
Regina P Markus
Andrew P Thomas
Célia RS Garcia
Antimalarial drugs disrupt ion homeostasis in malarial parasites
Memorias do Instituto Oswaldo Cruz
malaria
Plasmodium chabaudi
calcium
chloroquine
artemisinin
acidic compartment
title Antimalarial drugs disrupt ion homeostasis in malarial parasites
title_full Antimalarial drugs disrupt ion homeostasis in malarial parasites
title_fullStr Antimalarial drugs disrupt ion homeostasis in malarial parasites
title_full_unstemmed Antimalarial drugs disrupt ion homeostasis in malarial parasites
title_short Antimalarial drugs disrupt ion homeostasis in malarial parasites
title_sort antimalarial drugs disrupt ion homeostasis in malarial parasites
topic malaria
Plasmodium chabaudi
calcium
chloroquine
artemisinin
acidic compartment
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300012
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AT reginapmarkus antimalarialdrugsdisruptionhomeostasisinmalarialparasites
AT andrewpthomas antimalarialdrugsdisruptionhomeostasisinmalarialparasites
AT celiarsgarcia antimalarialdrugsdisruptionhomeostasisinmalarialparasites