| Journal: | Memorias do Instituto Oswaldo Cruz |
| Database: | PERIÓDICA |
| System number: | 000420040 |
| ISSN: | 0074-0276 |
| Authors: | Moreira, Douglas de Souza1 Duarte, Ana Paula1 Pais, Fabiano Sviatopolk Mirsky1 Silva-Pereira, Rosiane Aparecida da1 Romanha, Alvaro José1 Schenkman, Sergio2 Murta, Silvane Maria Fonseca1 |
| Institutions: | 1Fundacao Oswaldo Cruz, Instituto Rene Rachou, Belo Horizonte, Minas Gerais. Brasil 2Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Sao Paulo. Brasil |
| Year: | 2018 |
| Volumen: | 113 |
| Number: | 9 |
| Country: | Brasil |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Experimental, aplicado |
| English abstract | Eukaryotic initiation factor 5A (eIF5A) is a conserved protein with an essential role in translation elongation. Using one and two-dimensional western blotting, we showed that the eIF5A protein level was 2-fold lower in benznidazole (BZ)-resistant (BZR and 17LER) Trypanosoma cruzi populations than in their respective susceptible counterparts (BZS and 17WTS). To confirm the role of eIF5A in BZ resistance, we transfected BZS and 17WTS with the wild-type eIF5A or mutant eIF5A-S2A (in which serine 2 was replaced by alanine). Upon overexpressing eIF5A, both susceptible lines became approximately 3- and 5-fold more sensitive to BZ. In contrast, the eIF5A-S2A mutant did not alter its susceptibility to BZ. These data suggest that BZ resistance might arise from either decreasing the translation of proteins that require eIF5A, or as a consequence of differential levels of precursors for the hypusination reactions (e.g., spermidine and trypanothione), both of which alter BZ’s effects in the parasite |
| Disciplines: | Medicina |
| Keyword: | Parasitología, Bioquímica, Enfermedad de Chagas, Etiología, Resistencia a fármacos, Trypanosoma cruzi, Benznidazol, Factor de iniciación eucariótica |
| Keyword: | Parasitology, Biochemistry, Chagas disease, Etiology, Drug resistance, Trypanosoma cruzi, Benznidazole, Eukaryotic initiation factor |
| Full text: | Texto completo (Ver HTML) |
