Plasmodium falciparum: erythrocytic stages die by autophagic-like cell death under drug pressure.
It has been reported that an apoptotic cell death process can occur with protozoans, but no consensus on Plasmodium susceptibility to apoptosis was reached till now. Thus, we evaluated if Plasmodium falciparum blood forms undergo apoptosis after in vitro pressure with chloroquine, S-nitroso-N-acetyl-penicillamine (SNAP) or staurosporine. Inhibition of parasite growth and loss of viability were observed in treated cultures by both light microscopy and flow cytometry. When DNA fragmentation was verified, only a small number of TUNEL-positive parasites was detected in treated cultures and pretreatment of parasite with a general caspase inhibitor was not able to prevent parasite death. Considering the lack of apoptotic characteristics and the observation of parasites with cytoplasmatic vacuolization by electron microscopy, we conclude that P. falciparum parasites under chloroquine, SNAP or staurosporine pressures do not die by apoptosis but by a process similar to autophagy. The autophagic pathway could be explored as an alternative target for the development of new antimalarial drugs.
Totino
Paulo Renato Rivas
PR
Laboratory of Malaria Research, Instituto Oswaldo Cruz, Fiocruz, Pavilhão Leônidas Deane, Manguinhos, 21045-900 Rio de Janeiro, RJ, Brazil.
Daniel-Ribeiro
Cláudio Tadeu
CT
Corte-Real
Suzana
S
de Fátima Ferreira-da-Cruz
Maria
M
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D053938:DNA Fragmentation; D004912:Erythrocytes / Q000469:parasitology*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D020287:In Situ Nick-End Labeling; D008564:Membrane Potentials / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D020112:Rhodamine 123; D019311:Staurosporine / Q000494:pharmacology
D000962:Antimalarials; D061945:Caspase Inhibitors; D005456:Fluorescent Dyes; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D020112:Rhodamine 123; D002738:Chloroquine; D010396:Penicillamine; D019311:Staurosporine