Host cholesterol influences the activity of sterol biosynthesis inhibitors in Leishmania amazonensis.
Autor: | Andrade-Neto VV; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Tripanossomatídeos, Rio de Janeiro, RJ, Brasil., Manso PPA; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Patologia, Rio de Janeiro, RJ, Brasil., Pereira MG; Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Ultraestrutura Celular Hertha Meyer, Rio de Janeiro, RJ, Brasil., de Cicco NNT; Universidade Federal do Rio de Janeiro, Instituto de Bioquímica Médica, Rio de Janeiro, RJ, Brasil., Atella GC; Universidade Federal do Rio de Janeiro, Instituto de Bioquímica Médica, Rio de Janeiro, RJ, Brasil., Pelajo-Machado M; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Patologia, Rio de Janeiro, RJ, Brasil., Menna-Barreto RFS; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil., Torres-Santos EC; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Tripanossomatídeos, Rio de Janeiro, RJ, Brasil. |
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Jazyk: | angličtina |
Zdroj: | Memorias do Instituto Oswaldo Cruz [Mem Inst Oswaldo Cruz] 2022 Apr 04; Vol. 117, pp. e220407. Date of Electronic Publication: 2022 Apr 04 (Print Publication: 2022). |
DOI: | 10.1590/0074-02760220407 |
Abstrakt: | A significant percentage of exogenous cholesterol was found in promastigotes and amastigotes of all studied species of Leishmania, suggesting a biological role for this molecule. Previous studies have shown that promastigotes of Leishmania uptake more low-density lipoprotein (LDL) particles under pharmacological pressure and are more susceptible to ergosterol inhibition in the absence of exogenous sources of cholesterol. This work shows that the host's LDL is available to intracellular amastigotes and that the absence of exogenous cholesterol enhances the potency of sterol biosynthesis inhibitors in infected macrophages. A complete understanding of cholesterol transport to the parasitophorous vacuole can guide the development of a new drug class to be used in combination with sterol biosynthesis inhibitors for the treatment of leishmaniases. |
Databáze: | MEDLINE |
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