Effects of protein kinase inhibitors on the in vitro growth of Babesia bovis

Effects of protein kinase inhibitors on the in vitro growth of Babesia bovis
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DOI:
10.1017/s0031182006009917
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发表时间:
2006-06-01
期刊:
影响因子:
2.4
通讯作者:
Igarashi, I.
Igarashi, I.
中科院分区:
医学2区
文献类型:
--
作者:
Bork, S.;Das, S.;Igarashi, I.

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研究了丝氨酸/苏氨酸蛋白激酶、蛋白激酶C和钙调蛋白激酶抑制剂Staurosporine、Ro-31-7549和KN-93对牛巴贝斯虫体外生长的影响。Staurosporine是最有效的抑制剂,在100 μ m的浓度下,早在暴露的第一天就完全清除了寄生虫血症。此外,Staurosporine引起细胞外分裂子百分比的显著增加,很可能是由于抑制了寄生虫的红细胞入侵。虽然5毫米Ro-31-7549和KN-93有抑制作用,但这不足以消灭寄生虫。有趣的是,浓度为0-5至5 mm的KN-93影响了感染红细胞内的寄生发育。本研究表明,牛双球菌在一定程度上需要由寄生虫或宿主红细胞蛋白激酶介导的磷酸化,特别是在成功入侵红细胞和红细胞发育的过程中。
Staurosporine, Ro-31-7549, and KN-93, which are inhibitors of serine/threonine protein kinase, protein kinase C, and calcium-modulin kinase, respectively, were tested for their effects on the in vitro growth of Babesia bovis. Staurosporine was the most effective inhibitor, completely clearing the parasitaemia as early as the first day of exposure at a concentration of 100 mu M. Moreover, staurosporine caused a significant increase in the percentage of extracellular merozoites, most likely due to the inhibition of erythrocyte invasion by the parasite. Although 5 mm Ro-31-7549 and KN-93 had a suppressive action, this was not enough to destroy the parasite. Interestingly, concentrations of 0-5 to 5 mm KN-93 influenced the parasitic development within the infected erythrocytes. The present study suggests that B. bovis requires, to a certain extent, the phosphorylations mediated by parasite- or host erythrocyte-protein kinases, in particular, for the processes of successful invasion of erythrocytes and intraerythrocytic development.