Gametocytogenesis of Plasmodium falciparum in vitro: the cell-cycle
Gametocytogenesis of Plasmodium falciparum in vitro: the cell-cycle
复制标题
体外恶性疟原虫的配子细胞发生：细胞周期
作者：
R. Sinden;M. Smalley
恶性疟原虫配子母细胞在体外的可再生生长是从直接取自自然感染患者的环状阶段和从液氮中储存后的相同材料获得的。在微培养物中检查体外进行性分化9天的有限时间，并且为了方便起见，使用已建立的形态学标准将其分为5个阶段（Hawking，Wilson & Gammage，1971）。该微量培养系统适用于各种抗代谢物的生物测定。通过观察与对照培养物相比，实验培养物中建立的顺序发展模式的抑制来测量药物活性。所用的抑制剂针对DNA、RNA和蛋白质代谢以及微管组装。根据这些研究结果，提出恶性疟原虫的性细胞周期具有4个阶段的特征。(1)G1周期仅持续几个小时。(2)DNA合成发生的S期占据了发育的前2天的剩余时间-G1和S都局限于阶段I和II配子母细胞。(3)G2，它被细分为2个部分：G2 A，其特征在于阶段II和III配子体，其中显著的RNA和蛋白质合成继续发生;和G2 B，其中转录控制逐渐增加，导致RNA和蛋白质合成的抑制。尽管如此，继续形态分化发生在后一节转化的寄生虫阶段IV和形态和功能成熟的阶段V。最后的M期是由短暂的和爆炸性的事件配子发生，在此期间，发生进一步的蛋白质合成从头。建议的细胞周期检查作为一个模型的活性的配子杀化合物的研究。
SUMMARY Reproducible growth of gametocytes of Plasmodium falciparum in vitro was obtained from ring-stages taken directly from naturally infected patients and from the same material following storage in liquid nitrogen. Progressive sexual differentiation in vitro was examined for a finite period of 9 days in microcultures and was, for convenience, divided into 5 stages using established morphological criteria (Hawking, Wilson & Gammage, 1971). This microculture system was adapted as a bioassay for various anti-metabolites. Drug activity was measured by observing the inhibition of the established pattern of sequential development in experimental as compared to control cultures. Inhibitors used were directed against DNA, RNA and protein metabolism and microtubule assembly. As a result of these studies it is proposed that the sexual cell-cycle of P. falciparum is characterized by 4 phases. (1) A G1 period which lasts only a few hours. (2) The S phase, where DNA synthesis occurs, occupies the remainder of the first 2 days of development – both G1 and S are confined to stage I and II gametocytes. (3) G2, which is subdivided into 2 sections: G2A, characterized by stage II and III gametocytes, in which significant RNA and protein synthesis continue to occur; and G2B, where there is a progressive increase in transcription control resulting in the depression of both RNA and protein synthesis. Nonetheless, continued morphological differentiation occurs in the latter section transforming the parasites to stage IV and the morphologically and functionally mature stage V. The final M phase is marked by the brief and explosive events of gametogenesis, during which further protein synthesis occurs de novo. The proposed cell-cycle is examined as a model for studies on the activity of gametocytocidal compounds.