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
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
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DOI：
10.1111/j.1600-079x.2007.00486.x
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发表时间：
2007-11-01
影响因子：
10.3
通讯作者：
Garcia, Celia R. S.
中科院分区：
文献类型：
--
作者：
Beraldo, Flavlo H.;Mikoshiba, Katsuhiko;Garcia, Celia R. S.
疟疾寄生虫通过感知环境来调节自己的周期。了解恶性疟原虫在入侵、成熟以及再入侵前分裂的调控信号过程的机制将是一个重大突破，因此可能为治疗开辟新的途径。我们以前曾报道褪黑激素通过激活磷脂酶C（PLC）、产生InsP（3，）和诱导细胞内钙释放来调节疟原虫的昼夜节律。为了进一步研究褪黑激素作用的分子机制，我们在恶性疟原虫寄生虫培养物中使用InsP（3）调节剂2-氨基乙基二苯基硼酸酯（2-APB）。我们发现褪黑素通过InsP（3）信号作用于疟原虫细胞周期，2-APB阻断褪黑素对钙释放的作用。InsP（3）信号传导的功能可以被认为是疟原虫入侵和成熟过程中的重要事件，因为在疟原虫感染的红细胞中加入PLC抑制剂U 73122在体外削弱疟原虫入侵。通过使用8BrcAMP，我们还在这里报告说，疟原虫显示出一个'电容钙进入'的机制，在整个细胞质中的钙信号的放大。
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 InsP(3,) and induction of calcium release from intracellular stores. To further investigate the molecular mechanism of melatonin's action, we have used the InsP(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 InsP(3) signaling as 2-APB blocks melatonin's effect on calcium release. The function of the InsP(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 vitro. By using 8BrcAMP, we also report here that Plasmodia displays a 'capacitative calcium entry' mechanism for amplification of calcium signals throughout the cytoplasm.