Modulation of the growth of Plasmodium falciparum in vitro by protein serine/threonine phosphatase inhibitors.
To elucidate the physiological roles of the protein serine/threonine phosphatases of P. falciparum, first we identified and characterized phosphatase activities of Plasmodium falciparum enzymologically and pharmacologically. We have demonstrated that P. falciparum possesses phosphatase-1-like activities predominantly over phosphatase-2A-like activities, while erythrocytes possess mainly phosphatase-2A-like activities. Then, we examined the effects of okadaic acid and calyculin A, potent inhibitors of protein phosphatase 1 and 2A, on the growth of P. falciparum in vitro. Both of the drugs inhibited parasite growth dose dependently. The manner of growth inhibition by calyculin A and okadaic acid suggested that these drugs inhibit parasite growth mainly by inhibiting parasite phosphatase-1-like activities. Both drugs were shown to inhibit the growth of three different developmental stages of parasites--ring forms, trophozoites, and schizonts--and inhibit trophozoites the most. This is the first report on P. falciparum protein serine/threonine phosphatase activities, which are essential to regulate the erythrocytic stage of parasite growth.
Yokoyama
D
D
Department of Medical Zoology, Kobe University School of Medicine, Japan.
Saito-Ito
A
A
Asao
N
N
Tanabe
K
K
Yamamoto
M
M
Matsumura
T
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000469:parasitology; D008387:Marine Toxins; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000502:physiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development*; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D013997:Time Factors
D003470:Culture Media; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; D019319:Okadaic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2