Author | Rebello, Karina M. | |
Author | Andrade Neto, Valter V. | |
Author | Zuma, Aline A. | |
Author | Motta, Maria Cristina M. | |
Author | Gomes, Claudia Regina B. | |
Author | Souza, Marcus Vinícius N. de | |
Author | Atella, Geórgia C. | |
Author | Branquinha, Marta H. | |
Author | Santos, André L. S. | |
Author | Santos, Eduardo Caio Torres | |
Author | d`Avila-Levy, Claudia M. | |
Access date | 2018-10-09T11:32:44Z | |
Available date | 2018-10-09T11:32:44Z | |
Document date | 2018 | |
Citation | REBELLO, Karina M. et al. Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes. Parasitology, v.145, p.1304-1310, May 2018. | pt_BR |
ISSN | 0031-1820 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/29450 | |
Language | eng | pt_BR |
Publisher | Cambridge University Press | pt_BR |
Rights | restricted access | |
Subject in Portuguese | Aspartato | pt_BR |
Subject in Portuguese | Quimioterapia | pt_BR |
Subject in Portuguese | Leishmaniose | pt_BR |
Subject in Portuguese | Co-ínfecção | pt_BR |
Subject in Portuguese | tripanossomatídeos | pt_BR |
Title | Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes | pt_BR |
Type | Article | |
DOI | 10.1017/S0031182018000823 | |
Abstract | The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography-mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC-MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration-response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Síntese de Fármacos. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Síntese de Fármacos. 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 | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ. Brasil. | pt_BR |
Subject | Aspartyl | pt_BR |
Subject | chemotherapy | pt_BR |
Subject | co-infection | pt_BR |
Subject | leishmaniasis | pt_BR |
Subject | trypanosomatids | pt_BR |
e-ISSN | 1469-8161 | |
Embargo date | 2030-01-01 | |