Products of tryptophan catabolism induce Ca2+ release and modulate the cell cycle of Plasmodium falciparum malaria parasites.
Intraerythrocytic malaria parasites develop in a highly synchronous manner. We have previously shown that the host hormone melatonin regulates the circadian rhythm of the rodent malaria parasite, Plasmodium chabaudi, through a Ca2+-based mechanism. Here we show that melatonin and other molecules derived from tryptophan, i.e. N-acetylserotonin, serotonin and tryptamine, also modulate the cell cycle of human malaria parasite P. falciparum by inducing an increase in cytosolic free Ca2+. This occurs independently of the extracellular Ca2+ concentration, indicating that these molecules induce Ca2+ mobilization from intracellular stores in the trophozoite. This in turn leads to an increase in the proportion of schizonts. The effects of the indolamines in increasing cytosolic free Ca2+ and modulating the parasite cell cycle are both abrogated by an antagonist of the melatonin receptor, luzindole, and by the phospholipase inhibitor, U73122.
Beraldo
Flávio H
FH
Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de Sao Paulo, Sao Paulo, Brazil.
Garcia
Célia R S
CR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D010963:Plasmodium falciparum / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D014363:Tryptamines / Q000378:metabolism / Q000502:physiology; D014364:Tryptophan / Q000378:metabolism / Q000502:physiology*
D014363:Tryptamines; D012701:Serotonin; C030820:tryptamine; D014364:Tryptophan; D002118:Calcium