2-Cys peroxiredoxin TPx-1 is involved in gametocyte development in Plasmodium berghei

2-Cys peroxiredoxin TPx-1 is involved in gametocyte development in Plasmodium berghei
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DOI:
10.1016/j.molbiopara.2006.02.018
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发表时间:
2006-07-01
影响因子:
1.5
通讯作者:
Kawazu, Shin-ichiro
Kawazu, Shin-ichiro
中科院分区:
医学4区
文献类型:
--
作者:
Yano, Kazuhiko;Komaki-Yasuda, Kanako;Kawazu, Shin-ichiro

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过氧化物还原酶(Peroxiredoxins,Prxs)是一个广泛存在的抗氧化酶家族,参与细胞增殖和分化等多种细胞功能。为了研究典型的2-Cys Prx在疟疾寄生虫(TPx-1)中的生理作用,我们在啮齿动物疟疾寄生虫伯氏疟原虫(Plasmodium berghei,pbtpx-1)中破坏了该基因。基因破坏的寄生虫(Prx KO)在小鼠红细胞中正常发育,并在实验期间以与亲本菌株(WT)相似的速率繁殖。在10次传代后,正常生长速率没有改变,并且在细胞周期期间在寄生虫基因组中积累的8-羟基-2 '-脱氧鸟苷的水平在Prx KO和WT之间相似。这些结果表明,TPx-1不防止寄生虫DNA氧化,在哺乳动物的Prx相反,它不是必需的小鼠红细胞中的无性寄生虫生长。然而,Prx KO产生的配子母细胞,参与哺乳动物宿主和蚊子之间的过渡的有性阶段寄生虫,比WT少60%。配子体血症的高峰也延迟;然而,配子体的雄/雌比和雄配子体的出鞭毛活性正常。这些结果表明,TPx-1是所需的正常配子体发育,但不影响男性/女性配子体比例或男性配子发生。尽管PbTPx-1促进配子体发育的机制尚不清楚,但这些发现首次表明Prx参与了疟原虫的性发育。(c)2006 Elsevier B. V.保留所有权利。
Peroxiredoxins (Prxs) constitute a ubiquitous family of antioxidant enzymes involved in diverse cellular functions including cell proliferation and differentiation. To investigate the physiologic role of typical 2-Cys Prx in malaria parasites (TPx-1), we disrupted this gene in the rodent malaria parasite Plasmodium berghei (pbtpx-1). The gene-disrupted parasite (Prx KO) developed normally in mouse erythrocytes and multiplied at a rate similar to that of the parent strain (WT) during the experimental period. The normal growth rate was not altered after 10 passages, and the level of 8-hydroxy-2'-deoxyguanosine, which accumulates in the parasite genome during the cell cycle, was similar between Prx KO and WT. These results suggest that TPx-1 does not prevent parasite DNA oxidation, in contrast to mammalian Prx, and that it is not essential for asexual parasite growth in mouse erythrocytes. However, Prx KO produced up to 60% fewer gametocytes, sexual-stage parasites involved in the transition between the mammalian host and the mosquito, than WT did. The peak of gametocytemia was also delayed; however, the male/female ratio of gametocytes and the exflagellation activity of male gametocytes were normal. These results suggest that TPx-1 is required for normal gametocyte development but does not affect the male/female gametocyte ratio or male gametogenesis. Although the mechanism by which PbTPx-1 contributes to gametocyte development remains unknown, these findings suggest, for the first time, the involvement of Prx in the sexual development of the malaria parasite. (c) 2006 Elsevier B.V. All rights reserved.