Human malarial parasite, Plasmodium falciparum, displays capacitative calcium entry: 2-aminoethyl diphenylborinate blocks the signal transduction pathway of melatonin action on the P. falciparum cell cycle.
The malarial parasite senses the environment to modulate its own cycle. Knowledge of the mechanisms for regulation signaling processes at the invasion, maturation, as well as division of Plasmodium falciparum before reinvasion would represent a major breakthrough and, therefore, might open new avenues for therapy. We have previously reported that melatonin modulates the circadian rhythm of malarial parasites through the activation of phospholipase C (PLC), production of InsP3, and induction of calcium release from intracellular stores. To further investigate the molecular mechanism of melatonin's action, we have used the InsP3 modulator 2-aminoethyl diphenylborinate (2-APB) given in a culture of P. falciparum parasites. Here we show that the melatonin acts on Plasmodium cell cycle through InsP3 signaling as 2-APB blocks melatonin's effect on calcium release. The function of the InsP3 signaling can be regarded as an important event for parasite invasion and maturation process, since addition of the PLC inhibitor, U73122 into Plasmodium-infected red blood cells impairs parasite invasion in vitro. By using 8BrcAMP, we also report here that Plasmodia displays a 'capacitative calcium entry' mechanism for amplification of calcium signals throughout the cytoplasm.
Beraldo
Flávio H
FH
Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
Mikoshiba
Katsuhiko
K
Garcia
Célia R S
CR
D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008288:Malaria / Q000469:parasitology; D008550:Melatonin / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
D001896:Boron Compounds; D004963:Estrenes; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D015544:Inositol 1,4,5-Trisphosphate; C109986:2-aminoethoxydiphenyl borate; D008550:Melatonin; D002118:Calcium