Changklungmoa Narin, Kueakhai Pornanan, Apisawetakan Somjai, Riengrojpitak Suda, Sobhon Prasert, Chaithirayanon Kulathida
Department of Pathobiology, Faculty of Science, Mahidol University, Rama VI Rd, Bangkok, 10400, Thailand,
Parasitol Res. 2014 Jun;113(6):2335-43. doi: 10.1007/s00436-014-3888-7. Epub 2014 Apr 10.
In the present study, a cDNA encoding Trx from F. gigantica (FgTrx) was cloned by polymerase chain reaction (PCR). The sequence of FgTrx, analyzed by BLAST, SignalP, and ClustralW programs, showed 315 bp of an open reading frame (ORF), 12 bp 5'UTR, 78 bp 3'UTR, and the putative FgTrx peptide comprising of 104 amino acids, with a molecular weight of 11.68 kDa, with the active site containing five amino acids (tryptophan, cysteine, glycine, proline, cysteine) with a conserved dithiol motif from the two cysteines, and pI 5.86. The peptide had no signal sequence; hence, it was not a secreted protein. The recombinant FgTrx was expressed in Escherichia coli BL21 (DE3) and used for production for a polyclonal antibody in rabbits (anti-rFgTrx). The FgTrx protein expression, estimated by indirect ELISA using the rabbit anti-rFgTrx as probe, showed high levels in eggs, 2- and 4-week-old juveniles, and adult parasite. In a functional test, the rFgTrx exhibited specific activity that could be suppressed by an inhibitor (PX12). When tested by immunoblotting and immunohistochemistry, rabbit anti-rFgTrx reacted with natural FgTrx at a molecular weight of 11.68 kDa from eggs, metacercariae, NEJ, 2- and 4-week-old juveniles, and adult F. gigantica. The FgTrx protein was distributed at high levels in the tegument of 2- and 4-week-old juveniles, and the tegument, parenchyma, eggs, and reproductive organs of adult parasites. FgTrx may be one of the major factors acting against oxidative stresses that can damage the parasite; hence, it could be considered as a novel vaccine or drug target.
在本研究中,通过聚合酶链反应(PCR)克隆了来自巨片形吸虫(F. gigantica)的编码硫氧还蛋白(Trx)的cDNA。经BLAST、SignalP和ClustralW程序分析,巨片形吸虫硫氧还蛋白(FgTrx)序列显示有一个315 bp的开放阅读框(ORF)、12 bp的5'非翻译区(UTR)、78 bp的3'UTR,推测的FgTrx肽由104个氨基酸组成,分子量为11.68 kDa,活性位点包含五个氨基酸(色氨酸、半胱氨酸、甘氨酸、脯氨酸、半胱氨酸),两个半胱氨酸具有保守的二硫醇基序,等电点为5.86。该肽没有信号序列,因此它不是分泌蛋白。重组FgTrx在大肠杆菌BL21(DE3)中表达,并用于在兔中制备多克隆抗体(抗rFgTrx)。以兔抗rFgTrx为探针,通过间接ELISA估计FgTrx蛋白表达,结果显示在虫卵、2周龄和4周龄幼虫以及成虫期寄生虫中表达水平较高。在功能测试中,重组FgTrx表现出可被抑制剂(PX12)抑制的特定活性。通过免疫印迹和免疫组织化学检测时,兔抗rFgTrx与来自虫卵、尾蚴、新排出幼虫、2周龄和4周龄幼虫以及巨片形吸虫成虫的分子量为11.68 kDa的天然FgTrx发生反应。FgTrx蛋白在2周龄和4周龄幼虫的体表以及成虫期寄生虫的体表、实质、虫卵和生殖器官中高水平分布。FgTrx可能是抵抗可损害寄生虫的氧化应激的主要因素之一,因此,它可被视为一种新型疫苗或药物靶点。