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 compartments. The AO could be released from the parasite organelles by collapsing the pH gradient with the K+/H+ ionophore nigericin (20 microM), or by inhibiting the H+-pump with bafilomycin (4 microM). 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 microM 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.
Gazarini
Marcos L
ML
Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Súo Paulo, Brasil. cgarcia@usp.br
Sigolo
Carlos A O
CA
Markus
Regina P
RP
Thomas
Andrew P
AP
Garcia
Célia R S
CR
D000165:Acridine Orange; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D005456:Fluorescent Dyes; D006706:Homeostasis / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D016788:Plasmodium chabaudi / Q000187:drug effects*
D000962:Antimalarials; D037621:Artemisinins; D005456:Fluorescent Dyes; D007473:Ion Channels; D002738:Chloroquine; C031327:artemisinin; D000165:Acridine Orange