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Studies on cell-cycle synchronization in the asexual erythrocytic stages of Plasmodium falciparum.

机译:恶性疟原虫无性红细胞阶段细胞周期同步的研究。

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摘要

Multiplication of Plasmodium parasites within human erythrocytes is essential to malarial disease. The cell-division cycle of this organism, however, is still poorly understood. In other eukaryotes, various techniques for (apparent) cell-cycle synchronization have been used to shed light on the mechanisms involved in cell division and its control. Thus far there is no technique for cell-cycle synchronization (as opposed to selection of parasites of a limited age-range) in Plasmodium. We therefore investigated the possibility that inhibitors of DNA synthesis, the mitotic spindle, or cell-cycle control elements (such as cyclin-dependent kinases) could be used to synchronize P. falciparum cultures to a particular cell-cycle phase. Surprisingly, most of these compounds did not cause a block at a specific phase. Three compounds, Hoechst 33342, roscovitine and L-mimosine, did block development at the trophozoite-schizont transition (S or G2 phase). The block caused by the latter 2 inhibitors was reversible, suggesting that they might be used as synchronizing agents. However, a consideration of the perturbing effects of inhibitors and problems with 'batch' synchronization techniques in general lead us to believe that any results obtained using roscovitine- or L-mimosine-treated parasites may not be reflective of the normal cell cycle.
机译:人类红细胞内疟原虫的繁殖对疟疾至关重要。然而,这种生物的细胞分裂周期仍然知之甚少。在其他真核生物中,用于(表观)细胞周期同步的各种技术已被用于阐明细胞分裂及其控制所涉及的机制。迄今为止,在疟原虫中还没有用于细胞周期同步的技术(与选择年龄范围有限的寄生虫相反)。因此,我们研究了DNA合成抑制剂,有丝分裂纺锤体或细胞周期控制元件(如细胞周期蛋白依赖性激酶)可用于将恶性疟原虫培养物同步至特定细胞周期相的可能性。出乎意料的是,这些化合物中的大多数在特定阶段都不会引起阻塞。 Hoechst 33342,roscovitine和L-mimosine这三种化合物确实在滋养体-裂殖体转变(S或G2相)时阻止了发育。后两种抑制剂引起的阻滞是可逆的,表明它们可用作同步剂。但是,考虑到抑制剂的干扰作用和“批处理”同步技术的问题,通常使我们相信,使用roscovitine或L-mimosine处理过的寄生虫获得的任何结果均不能反映正常的细胞周期。

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