The interplay between tubulins and P450 cytochromes during Plasmodium berghei invasion of Anopheles gambiae midgut.
The interplay between tubulins and P450 cytochromes during Plasmodium berghei invasion of Anopheles gambiae midgut.
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DOI：
10.1371/journal.pone.0024181
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Silveira H
中科院分区：
文献类型：
--
作者：
Félix RC;Silveira H
疟原虫感染增加了蚊子体内的氧化应激，导致冈比亚按蚊解毒基因转录的显著改变。在这些解毒基因中，几个P450细胞色素和微管蛋白的表达不同，这表明它们参与了蚊子对寄生虫入侵的反应。P450细胞色素通常参与几种化合物的代谢和解毒，但也受到几种病原体的调节，包括疟疾寄生虫。微管蛋白作为细胞骨架的组成部分是极其重要的，其重排功能是对疟原虫入侵的反应。利用基因沉默技术研究了细胞色素P450还原酶、微管蛋白A和微管蛋白B沉默对A.冈比亚应对伯氏疟原虫入侵。微管蛋白在抗感染过程中的作用也通过抑制它们的作用进行了研究。将秋水仙碱、长春碱和紫杉醇三种不同的微管蛋白抑制剂注入A.冈比亚蚊子。注射后24小时，这些蚊子通过来自感染的CD 1小鼠的血餐感染伯氏疟原虫。使用RT-qPCR测量细胞色素P450基因表达以检测沉默、抑制和对照蚊子之间细胞色素表达的差异。结果表明，细胞色素P450还原酶的沉默，以及微管蛋白（A和B）的沉默和抑制影响疟原虫感染的效率。沉默和抑制也影响细胞色素P450的表达水平。我们的研究结果表明，微管蛋白和P450细胞色素之间存在的关系，在A。冈比亚对伯氏疟原虫入侵的免疫应答。在这项研究中，P450细胞色素之一，CYP 6 Z2，突出作为这种关联的潜在联系。需要进一步的工作来充分了解微管蛋白基因在疟原虫感染反应中的作用。
Plasmodium infection increases the oxidative stress inside the mosquito, leading to a significant alteration on transcription of Anopheles gambiae detoxification genes. Among these detoxification genes several P450 cytochromes and tubulins were differently expressed, suggesting their involvement in the mosquito's response to parasite invasion. P450 cytochromes are usually involved in the metabolism and detoxification of several compounds, but are also regulated by several pathogens, including malaria parasite. Tubulins are extremely important as components of the cytoskeleton, which rearrangement functions as a response to malaria parasite invasion. Gene silencing methods were used to uncover the effects of cytochrome P450 reductase, tubulinA and tubulinB silencing on the A. gambiae response to Plasmodium berghei invasion. The role of tubulins in counter infection processes was also investigated by inhibiting their effect. Colchicine, vinblastine and paclitaxel, three different tubulin inhibitors were injected into A. gambiae mosquitoes. Twenty-four hours post injection these mosquitoes were infected with P. berghei through a blood meal from infected CD1 mice. Cytochrome P450 gene expression was measured using RT-qPCR to detect differences in cytochrome expression between silenced, inhibited and control mosquitoes. Results showed that cytochrome P450 reductase silencing, as well as tubulin (A and B) silencing and inhibition affected the efficiency of Plasmodium infection. Silencing and inhibition also affected the expression levels of cytochromes P450. Our results suggest the existence of a relationship between tubulins and P450 cytochromes during A. gambiae immune response to P. berghei invasion. One of the P450 cytochromes in this study, CYP6Z2, stands out as the potential link in this association. Further work is needed to fully understand the role of tubulin genes in the response to Plasmodium infection.
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