Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Division of Signaling Biology, Ontario Cancer Institute, Toronto, ON, Canada M5G 1L7.
Sci Rep. 2014 Feb 28;4:4231. doi: 10.1038/srep04231.
Chagas disease is caused by an intracellular parasitic protist, Trypanosoma cruzi. As there are no highly effective drugs against this agent that also demonstrate low toxicity, there is an urgent need for development of new drugs to treat Chagas disease. We have previously demonstrated that the parasite inositol 1,4,5-trisphosphate receptor (TcIP3R) is crucial for invasion of the mammalian host cell by T. cruzi. Here, we report that TcIP3R is a short-lived protein and that its expression is significantly suppressed in trypomastigotes. Treatment of trypomastigotes, an infective stage of T. cruzi, with antisense oligonucleotides specific to TcIP3R deceased TcIP3R protein levels and impaired trypomastigote invasion of host cells. Due to the resulting instability and very low expression level of TcIP3R in trypomastigotes indicates that TcIP3R is a promising target for antisense therapy in Chagas disease.
克氏锥虫病是由一种细胞内寄生原生动物，即克氏锥虫引起的。由于目前尚无高效低毒的药物来治疗这种病原体，因此迫切需要开发新的药物来治疗克氏锥虫病。我们之前已经证明，寄生虫肌醇 1,4,5-三磷酸受体（TcIP3R）对于克氏锥虫入侵哺乳动物宿主细胞至关重要。在这里，我们报告称 TcIP3R 是一种短寿命蛋白，其在游离体中的表达受到显著抑制。用针对 TcIP3R 的反义寡核苷酸处理游离体（克氏锥虫的感染阶段）可降低 TcIP3R 蛋白水平并损害游离体入侵宿主细胞的能力。由于游离体中 TcIP3R 的不稳定性和极低表达水平，这表明 TcIP3R 是克氏锥虫病抗反义治疗的一个有前途的靶点。
