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

摘要

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 Ins P_3 and induction of calcium release from intracellular stores. To further investigate the molecular mechanism of melatonin's action, we have used the Ins P_3 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 Ins P_3 signaling as 2-APB blocks melatonin's effect on calcium release. The function of the Ins P_3 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 yitro. By using 8Brc AMP, we also report here that Plasmodia displays a 'capacitative calcium entry' mechanism for amplification of calcium signals throughout the cytoplasm.