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首页> 外文期刊>Parasitology >Naphthoimidazoles promote different death phenotypes in Trypanosoma cruzi.
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Naphthoimidazoles promote different death phenotypes in Trypanosoma cruzi.

机译：萘并咪唑在克氏锥虫中促进不同的死亡表型。

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摘要

SUMMARY: In a screening of 65 derivatives of natural quinones using bloodstream trypomastigotes of Trypanosoma cruzi, the 3 naphthoimidazoles derived from beta-lapachone - N1, N2 and N3--were selected as the most active. Investigation of their mode of action led to the characterization of mitochondrion, reservosomes and DNA as their main targets, and stimulated further studies on death pathways. Ultrastructural analysis revealed both autophagic (autophagosomes) and apoptotic-like (membrane blebbing) phenotypes. Flow cytometry analysis showed, in N2-treated trypomastigotes, a small increase of phosphatidylserine exposure, and a large increase in the percentage of necrosis, caused by N1 or N2. These death phenotypes were not detected in treated epimastigotes. The strong increase in labelling of monodansyl cadaverine, the inhibition of the death process by wortmannin or 3-methyladenine, the overexpression of ATG genes in treated epimastigotes, together with ultrastructural evidence point to autophagy as the predominant phenotype induced by the naphthoimidazoles. However, there are other pathways occurring concomitantly with variable intensities, justifying the need to detail the molecular features involved.
机译：摘要：在使用克氏锥虫的血流锥虫对65种天然醌的衍生物进行筛选时，从β-lapachone衍生的3种萘咪唑-N1，N2和N3-被选为活性最高的。对它们的作用方式的研究导致了线粒体，贮库和DNA作为其主要靶标的表征，并激发了对死亡途径的进一步研究。超微结构分析显示自噬（自噬体）和凋亡样（膜起泡）表型。流式细胞仪分析显示，在由N2处理过的锥虫中，由N1或N2引起的磷脂酰丝氨酸暴露量有少量增加，而坏死百分率则有较大增加。这些死亡表型未在治疗的附鞭毛虫中检测到。单丹磺胺尸胺的标记的大量增加，渥曼青霉素或3-甲基腺嘌呤对死亡过程的抑制作用，经处理的兽鞭tig科动物中ATG基因的过度表达以及超微结构证据表明，自噬是萘咪唑诱导的主要表型。然而，还有其他途径伴随强度的变化而发生，证明有必要详述涉及的分子特征。

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