N1-acetyl-N2-formyl-5-methoxykynuramine modulates the cell cycle of malaria parasites.
We previously reported that intraerythrocytic malaria parasites have their development synchronized by melatonin and other products of tryptophan catabolism (i.e. serotonin, N-acetylserotonin and tryptamine). Here, we show that N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), a product of melatonin degradation, synchronizes Plasmodium chabaudi and Plasmodium falciparum. The synchronization is abrogated with a melatonin receptor antagonist, luzindole. We established quantitatively that a differential AFMK production occurred within the intraerythrocytic stages of rodent malaria parasite Plasmodium chabaudi (ring, trophozoite and schizont), when the infected erythrocytes were previously incubated with melatonin. Measurement of AFMK formation in P. chabaudi after incubation with melatonin at a concentration of 500 nmol/L revealed the following values for AFMK production: ring 0.1 +/- 0.1 nmol/L, trophozoite 22.9 +/- 0.5 nmol/L, schizont 29 +/- 5 nmol/L. Confocal and spectrofluorophotometer experiments with isolated parasites and infected-RBC, loaded with calcium indicator Fluo-4 showed that AFMK elicits an increase in the cytosol calcium concentration in these parasites. Our data suggest that AFMK could have an important role in modulating the cell cycle of malaria parasites mainly in the late stages (trophozoite and schizont).
Budu
Alexandre
A
Departamento de Fisiologia, Instituto de Biociências, Universidade of São Paulo, São Paulo, Brazil.
Peres
Rafael
R
Bueno
Vânia Blasques
VB
Catalani
Luiz Henrique
LH
Garcia
Célia Regina da Silva
CR
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D007735:Kynuramine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008550:Melatonin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016788:Plasmodium chabaudi / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*
D007735:Kynuramine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D008550:Melatonin