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Alpha-terthienyl increases filamentous actin of Entamoeba histolytica
Molecular and Biochemical Parasitology ( IF 1.5 ) Pub Date : 2022-09-06 , DOI: 10.1016/j.molbiopara.2022.111512
Mayra Herrera-Martínez 1 , Verónica Ivonne Hernández-Ramírez 2 , Sarita Montaño 3 , Bibiana Chávez-Munguía 2 , Beatriz Hernández-Carlos 4 , Patricia Talamás-Rohana 2
Affiliation  

This study aimed to know if alpha terthienyl (α-T) affects E. histolytica viability and to analyze its effect on the actin cytoskeleton. Trophozoites of E. histolytica HM1-IMSS were treated with α-T, then, cell viability and morphology were evaluated using tetrazolium salts and scanning electron microscopy, respectively; while actin filaments (F-actin) were stained with rhodamine-phalloidin, observed by confocal microscopy and quantified by fluorometry. Data showed that α-T inhibited cell viability of trophozoites (IC50, 19.43 µg / mL), affected the cell morphology, and increased the F-actin in a dose-dependent manner. Production of reactive oxygen species and RhoA-GTP levels remained normal in α-T-treated amebas. Two inhibitors that affect the organization of the trophozoites cytoskeleton, one that interacts directly with actin, Cytochalasin D (CD), and one that affects the Rho signaling pathway by inhibiting the downstream effector Rock, Y27632, were tested. Y27632 did not affect the increase of polymerized actin observed with α-T, this compound partially ameliorates the potent disrupting effects of CD on actin filaments. Docking results suggest that α-T could be an antagonist of CD for the same interaction zone in actin, however, more studies are needed to define the action mechanism of this compound.



中文翻译:

α-三噻吩增加溶组织内阿米巴的丝状肌动蛋白

本研究旨在了解 alpha terthienyl (α-T) 是否影响E. histolytica的生存能力,并分析其对肌动蛋白细胞骨架的影响。用 α-T 处理E. histolytica HM1-IMSS 的滋养体,然后分别使用四唑盐和扫描电子显微镜评估细胞活力和形态;而肌动蛋白丝 (F-肌动蛋白) 用罗丹明-鬼笔环肽染色,通过共聚焦显微镜观察并通过荧光测定法定量。数据显示α-T抑制滋养体的细胞活力(IC 50, 19.43 µg / mL), 影响细胞形态, 并以剂量依赖的方式增加 F-肌动蛋白。活性氧的产生和 RhoA-GTP 水平在 α-T 处理的变形虫中保持正常。测试了影响滋养体细胞骨架组织的两种抑制剂,一种直接与肌动蛋白相互作用,细胞松弛素 D (CD),另一种通过抑制下游效应子 Rock Y27632 影响 Rho 信号通路。Y27632 不影响用 α-T 观察到的聚合肌动蛋白的增加,该化合物部分改善了 CD 对肌动蛋白丝的有效破坏作用。对接结果表明,对于肌动蛋白中相同的相互作用区,α-T 可能是 CD 的拮抗剂,但是,需要更多的研究来确定该化合物的作用机制。

更新日期:2022-09-06
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