Antisense oligonucleotides targeting parasite inositol 1,4,5-trisphosphate receptor inhibits mammalian host cell invasion by Trypanosoma cruzi. 2014

Muneaki Hashimoto, and Takeshi Nara, and Hiroko Hirawake, and Jorge Morales, and Masahiro Enomoto, and Katsuhiko Mikoshiba
Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

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.

UI MeSH Term Description Entries
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006790 Host-Parasite Interactions The relationship between an invertebrate and another organism (the host), one of which lives at the expense of the other. Traditionally excluded from definition of parasites are pathogenic BACTERIA; FUNGI; VIRUSES; and PLANTS; though they may live parasitically. Host-Parasite Relations,Parasite-Host Relations,Host-Parasite Relationship,Parasite-Host Interactions,Host Parasite Interactions,Host Parasite Relations,Host Parasite Relationship,Host-Parasite Interaction,Host-Parasite Relation,Host-Parasite Relationships,Interaction, Host-Parasite,Interaction, Parasite-Host,Interactions, Host-Parasite,Interactions, Parasite-Host,Parasite Host Interactions,Parasite Host Relations,Parasite-Host Interaction,Parasite-Host Relation,Relation, Host-Parasite,Relation, Parasite-Host,Relations, Host-Parasite,Relations, Parasite-Host,Relationship, Host-Parasite,Relationships, Host-Parasite
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014349 Trypanosoma cruzi The agent of South American trypanosomiasis or CHAGAS DISEASE. Its vertebrate hosts are man and various domestic and wild animals. Insects of several species are vectors. Trypanosoma cruzus,cruzi, Trypanosoma
D015316 Genetic Therapy Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions. Gene Therapy,Somatic Gene Therapy,DNA Therapy,Gene Therapy, Somatic,Genetic Therapy, Gametic,Genetic Therapy, Somatic,Therapy, DNA,Therapy, Gene,Therapy, Somatic Gene,Gametic Genetic Therapies,Gametic Genetic Therapy,Genetic Therapies,Genetic Therapies, Gametic,Genetic Therapies, Somatic,Somatic Genetic Therapies,Somatic Genetic Therapy,Therapies, Gametic Genetic,Therapies, Genetic,Therapies, Somatic Genetic,Therapy, Gametic Genetic,Therapy, Genetic,Therapy, Somatic Genetic
D015544 Inositol 1,4,5-Trisphosphate Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. 1,4,5-InsP3,Inositol 1,4,5-Triphosphate,Myo-Inositol 1,4,5-Trisphosphate,1,4,5-IP3,Myoinositol 1,4,5-Triphosphate
D016376 Oligonucleotides, Antisense Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize. Anti-Sense Oligonucleotide,Antisense Oligonucleotide,Antisense Oligonucleotides,Anti-Sense Oligonucleotides,Anti Sense Oligonucleotide,Anti Sense Oligonucleotides,Oligonucleotide, Anti-Sense,Oligonucleotide, Antisense,Oligonucleotides, Anti-Sense
D016475 3T3 Cells Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION. 3T3 Cell,Cell, 3T3,Cells, 3T3
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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