Antimalarial drugs disrupt ion homeostasis in malarial parasites

Detalhes bibliográficos
Autor(a) principal: Gazarini,Marcos L
Data de Publicação: 2007
Outros Autores: Sigolo,Carlos AO, Markus,Regina P, Thomas,Andrew P, Garcia,Célia RS
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Memórias do Instituto Oswaldo Cruz
Texto Completo: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300012
Resumo: 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 Antimalarial drugs disrupt ion homeostasis in malarial parasitesmalariaPlasmodium chabaudicalciumchloroquineartemisininacidic compartmentPlasmodium 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.Instituto Oswaldo Cruz, Ministério da Saúde2007-06-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300012Memórias do Instituto Oswaldo Cruz v.102 n.3 2007reponame:Memórias do Instituto Oswaldo Cruzinstname:Fundação Oswaldo Cruzinstacron:FIOCRUZ10.1590/S0074-02762007000300012info:eu-repo/semantics/openAccessGazarini,Marcos LSigolo,Carlos AOMarkus,Regina PThomas,Andrew PGarcia,Célia RSeng2020-04-25T17:49:50Zhttp://www.scielo.br/oai/scielo-oai.php0074-02761678-8060opendoar:null2020-04-26 02:14:37.055Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruztrue
dc.title.none.fl_str_mv Antimalarial drugs disrupt ion homeostasis in malarial parasites
title Antimalarial drugs disrupt ion homeostasis in malarial parasites
spellingShingle Antimalarial drugs disrupt ion homeostasis in malarial parasites
Gazarini,Marcos L
malaria
Plasmodium chabaudi
calcium
chloroquine
artemisinin
acidic compartment
title_short 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_sort Antimalarial drugs disrupt ion homeostasis in malarial parasites
author Gazarini,Marcos L
author_facet Gazarini,Marcos L
Sigolo,Carlos AO
Markus,Regina P
Thomas,Andrew P
Garcia,Célia RS
author_role author
author2 Sigolo,Carlos AO
Markus,Regina P
Thomas,Andrew P
Garcia,Célia RS
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Gazarini,Marcos L
Sigolo,Carlos AO
Markus,Regina P
Thomas,Andrew P
Garcia,Célia RS
dc.subject.por.fl_str_mv malaria
Plasmodium chabaudi
calcium
chloroquine
artemisinin
acidic compartment
topic malaria
Plasmodium chabaudi
calcium
chloroquine
artemisinin
acidic compartment
dc.description.none.fl_txt_mv 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.
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.
publishDate 2007
dc.date.none.fl_str_mv 2007-06-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300012
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762007000300012
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S0074-02762007000300012
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Instituto Oswaldo Cruz, Ministério da Saúde
publisher.none.fl_str_mv Instituto Oswaldo Cruz, Ministério da Saúde
dc.source.none.fl_str_mv Memórias do Instituto Oswaldo Cruz v.102 n.3 2007
reponame:Memórias do Instituto Oswaldo Cruz
instname:Fundação Oswaldo Cruz
instacron:FIOCRUZ
reponame_str Memórias do Instituto Oswaldo Cruz
collection Memórias do Instituto Oswaldo Cruz
instname_str Fundação Oswaldo Cruz
instacron_str FIOCRUZ
institution FIOCRUZ
repository.name.fl_str_mv Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruz
repository.mail.fl_str_mv
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