| Author | Andrade Neto, Valter Viana | |
| Author | Cicco, Nuccia Nicole Theodore | |
| Author | Cunha Junior, Edézio Ferreira | |
| Author | Canto-Cavalheiro, Marilene Marcuzzo | |
| Author | Atella, Georgia Correa | |
| Author | Santos, Eduardo Caio Torres | |
| Access date | 2018-11-17T17:50:24Z | |
| Available date | 2018-11-17T17:50:24Z | |
| Document date | 2011 | |
| Citation | ANDRADE NETO, Valter Viana; et al. The pharmacological inhibition of sterol biosynthesis in Leishmania is counteracted by enhancement of LDL endocytosis. Acta tropica, v.119, n.2-3, p.194-198, Aug. 2011. | pt_BR |
| ISSN | 0001-706X | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/30063 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Leishmania | pt_BR |
| Subject in Portuguese | Colesterol | pt_BR |
| Subject in Portuguese | LDL | pt_BR |
| Subject in Portuguese | Esterol | pt_BR |
| Subject in Portuguese | Quimioterapia | pt_BR |
| Subject in Portuguese | azólicos | pt_BR |
| Title | The pharmacological inhibition of sterol biosynthesis in Leishmania is counteracted by enhancement of LDL endocytosis | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.actatropica.2011.05.001 | |
| Abstract | Leishmania parasites, despite being able to synthesize their own sterols, acquire and accumulate significant amounts of cholesterol through low density lipoprotein (LDL) particle endocytosis. The role of this system in Leishmania amazonensis promastigotes under pharmacological pressure by sterol biosynthesis inhibitors (SBIs) was investigated. First, thin layer chromatography demonstrated that L. amazonensis promastigotes, in response to ergosterol biosynthesis inhibition by treatment with 4.0 and 6.0 μM ketoconazole or miconazole, accumulate up to two times more cholesterol than controls. The treatment of promastigotes with ketoconazole and simvastatin, two SBIs with non-related mechanisms of action, showed that both drugs induce increases in (125)I-LDL endocytosis in a dose-dependent manner, indicating that the accumulation of exogenous cholesterol is due to the enhancement of LDL uptake. Finally, it was demonstrated that L. amazonensis promastigotes were rendered more susceptible to treatment with SBIs (ketoconazole, miconazole, simvastatin and terbinafine) in the absence of exogenous cholesterol sources, with a reduction of the IC50s of about 50% in three of the four tested drugs. These results show that the exogenous cholesterol uptake system in L. amazonensis plays a role as a compensatory mechanism in response to the presence of SBIs, suggesting that it may be a potential pharmacological target. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Leishmania | pt_BR |
| Subject | Sterol | pt_BR |
| Subject | Cholesterol | pt_BR |
| Subject | Chemotheraphy | pt_BR |
| Subject | LDL | pt_BR |
| Subject | Azoles | pt_BR |
| Embargo date | 2030-01-01 | |
