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首页> 外文期刊>Parasitology >Apis mellifera venom induces different cell death pathways in Trypanosoma cruzi.
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Apis mellifera venom induces different cell death pathways in Trypanosoma cruzi.

机译：蜜蜂蜜蜂毒液在克氏锥虫中诱导不同的细胞死亡途径。

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SUMMARY Chagas disease chemotherapy is based on drugs that exhibit toxic effects and have limited efficacy, such as Benznidazole. Therefore, research into new chemotherapeutic agents from natural sources needs to be exploited. Apis mellifera venom consists of many biologically active molecules and has been reported to exhibit remarkable anti-cancer effects, often promoting an apoptosis-like death phenotype. This study demonstrates that A. mellifera venom can affect the growth, viability and ultrastructure of all Trypanosoma cruzi developmental forms, including intracellular amastigotes, at concentrations 15- to 100-fold lower than those required to cause toxic effects in mammalian cells. The ultrastructural changes induced by the venom in the different developmental forms led us to hypothesize the occurrence of different programmed cell death pathways. Autophagic cell death, characterized by the presence of autophagosomes-like organelles and a strong monodansyl cadaverine labelling, appears to be the main death mechanism in epimastigotes. In contrast, increased TUNEL staining, abnormal nuclear chromatin condensation and kDNA disorganization was observed in venom-treated trypomastigotes, suggesting cell death by an apoptotic mechanism. On the other hand, intracellular amastigotes presented a heterogeneous cell death phenotype profile, where apoptosis-like death seemed to be predominant. Our findings confirm the great potential of A. mellifera venom as a source for the development of new drugs for the treatment of neglected diseases such as Chagas disease.
机译：发明内容查加斯病化学疗法基于表现出毒性作用且功效有限的药物，例如苯乙唑。因此，需要开发对来自自然资源的新化学治疗剂的研究。蜜蜂蜜蜂毒液由许多具有生物活性的分子组成，据报道具有明显的抗癌作用，通常促进细胞凋亡样死亡表型。这项研究表明，A。mellifera毒液可以影响所有克鲁斯锥虫的发育形式（包括细胞内变形虫）的生长，活力和超微结构，其浓度比在哺乳动物细胞中引起毒性作用所需的浓度低15至100倍。毒液以不同的发育形式诱导的超微结构变化使我们假设发生了不同的程序性细胞死亡途径。自噬细胞死亡的特征是自噬体样细胞器的存在和强烈的单丹酰尸胺标记，似乎是副鞭毛虫的主要死亡机制。相比之下，在用毒液处理的锥虫中观察到TUNEL染色增加，核染色质凝集异常和kDNA异常，这表明细胞是通过凋亡机制死亡的。另一方面，胞内变形虫呈现出异质性细胞死亡表型特征，其中凋亡样死亡似乎占主导。我们的发现证实，A。mellifera毒液具有巨大的潜力，可作为开发用于治疗被忽视疾病（例如南美锥虫病）的新药的来源。

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