Effect of jasplakinolide on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum.
The effect of jasplakinolide (JAS), an actin-polymerizing and filament-stabilizing drug, on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum was examined. Jasplakinolide markedly decreased the parasitemia in a synchronized culture of P. falciparum strain FCR-3 in a time- and concentration-dependent manner. The decrease became evident at day 2 at concentrations of 0.3 micro M and above, and parasites finally disappeared at day 4. Giemsa-stained smears of P. falciparum-infected erythrocytes demonstrated that there was no effect on the development of schizonts from ring forms. Merozoites were released from the infected erythrocytes in a normal manner with and without JAS. However, there were no ring form-infected erythrocytes when JAS was administered, even after the release of merozoites. This indicates that the merozoites exposed to JAS failed to invade erythrocytes. The inhibitory effect of JAS on the parasitemia was reversed by the removal of the drug after exposure to 1 micro M of JAS for 1 day. Electron microscopy revealed that the merozoites treated with JAS showed a protrusion of the apical end which contained the microfilament structure. Immunoblot analysis indicated that the JAS treatment increased F-actin filaments of merozoites but had no effect on those of the trophozoites and schizonts. Therefore, this study demonstrated that JAS has an antimalarial activity.
Mizuno
Yasutaka
Y
Department of Tropical Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.
Makioka
Asao
A
Kawazu
Shin-ichiro
S
Kano
Shigeyuki
S
Kawai
Satoru
S
Akaki
Mayumi
M
Aikawa
Masamichi
M
Ohtomo
Hiroshi
H
D008841:Actin Cytoskeleton / Q000187:drug effects*; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003470:Culture Media; D047630:Depsipeptides; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity / Q000648:ultrastructure
D000199:Actins; D000981:Antiprotozoal Agents; D003470:Culture Media; D047630:Depsipeptides; D010456:Peptides, Cyclic; C057531:jasplakinolide