Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Tripanossomatídeos, Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Patologia, Rio de Janeiro, RJ, Brasil.
Mem Inst Oswaldo Cruz. 2022 Apr 4;117:e220407. doi: 10.1590/0074-02760220407. eCollection 2022.
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.
在外源胆固醇中发现有很大一部分存在于所有研究的利什曼原虫的前鞭毛体和无鞭毛体中，这表明该分子具有生物学作用。先前的研究表明，在药理学压力下，利什曼原虫摄取更多的低密度脂蛋白（LDL）颗粒，并且在没有外源胆固醇的情况下更容易受到麦角固醇抑制。这项工作表明，宿主的 LDL 可用于细胞内无鞭毛体，并且缺乏外源胆固醇会增强感染巨噬细胞中固醇生物合成抑制剂的效力。对外源胆固醇转运到滋养体空泡的全面了解可以指导开发新的药物类别，与固醇生物合成抑制剂联合用于治疗利什曼病。
