Calcium-dependent modulation by melatonin of the circadian rhythm in malarial parasites.
Calcium-dependent modulation by melatonin of the circadian rhythm in malarial parasites.
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DOI：
10.1038/35017112
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发表时间：
2000-07-01
影响因子：
21.3
通讯作者：
Garcia, CRS
中科院分区：
文献类型：
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作者：
Hotta, CT;Gazarini, ML;Garcia, CRS
* Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo 05508-90, Brasil† Dipartimento di Scienze Biomediche Sperimentali, Centro CNR ‘Biomembrane’, Universita’di Padova, Padova 35121, Italy.‡ 电子邮件：cgarcia@ usp。疟疾寄生虫的发育是一个复杂的过程，涉及细胞内和细胞外阶段。红细胞内的成熟通过明确的阶段进行，称为环、滋养体和裂殖体。在体内，向新阶段的转变和新红细胞的入侵是高度同步的1。这些过程的时间因疟原虫种类而异，但始终是 24 小时的倍数。血液中数十亿个体寄生虫的同时出现可能代表了逃避宿主防御机制的有效进化策略。这些过程的同步性在培养物中很快消失，表明可能涉及宿主来源的信号，尽管该信号的性质目前尚不清楚。在这里，我们证明褪黑激素激素在体外改变疟疾寄生虫的发育，体内松果体手术消融导致疟原虫成熟过程的同步性降低，这种效应在褪黑激素治疗后被逆转，并且体内褪黑激素受体的抑制模仿了松果体切除术的效果。我们还证明，褪黑激素通过激活与磷脂酶 C 偶联的特定受体，导致体外生长的疟原虫细胞内储存的 Ca2+ 释放。因此，我们认为宿主体内褪黑激素浓度的昼夜变化是控制褪黑激素同步成熟的关键信号。
* Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo 05508-90, Brasil† Dipartimento di Scienze Biomediche Sperimentali, Centro CNR ‘Biomembrane’, Universita’di Padova, Padova 35121, Italy.‡ e-mail: cgarcia@ usp. br he development of malarial parasites is a complex process involving both intracellular and extracellular phases. Intraerythrocytic maturation proceeds through well-defined stages, termed rings, trophozoites and schizonts. In vivo, transition to a new stage and invasion of new erythrocytes are highly synchronous1. The timing of these processes varies between Plasmodium species, but is always a multiple of 24 h. The simultaneous appearance of billions of individual parasites in the bloodstream may represent an efficient evolutionary strategy to escape the defence mechanisms of the host. The synchronicity of these processes is rapidly lost in culture, indicating the possible involvement of a host-derived signal, although the nature of this signal is presently unknown. Here we show that the hormone melatonin modifies the development of malarial parasites in vitro, that in vivo surgical ablation of the pineal gland leads to reduced synchronicity in the maturation process of Plasmodium, an effect that is reversed upon treatment with melatonin, and that in vivo inhibition of melatonin receptors mimics the effect of pinealectomy. We also demonstrate that melatonin, through activation of specific receptors coupled to phospholipase C activation, causes release of Ca2+ from the intracellular stores of Plasmodium grown in vitro. We therefore propose that circadian changes in melatonin concentration in the host represent a key signal that controls synchronous maturation of