Alpha-terthienyl increases filamentous actin of Entamoeba histolytica

IF 1.4 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular and biochemical parasitology Pub Date : 2022-11-01 DOI:10.1016/j.molbiopara.2022.111512
Mayra Herrera-Martínez , Verónica Ivonne Hernández-Ramírez , Sarita Montaño , Bibiana Chávez-Munguía , Beatriz Hernández-Carlos , Patricia Talamás-Rohana
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Abstract

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.

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-巯基增加溶组织内阿米巴的丝状肌动蛋白
本研究旨在了解α-三烯基(α-T)是否影响溶组织芽胞杆菌的生存能力,并分析其对肌动蛋白细胞骨架的影响。用α-T处理溶组织芽孢杆菌HM1-IMSS滋养体,分别用四氮唑盐和扫描电镜观察细胞活力和形态;罗丹明-phalloidin染色肌动蛋白丝(F-actin),共聚焦显微镜观察,荧光定量。结果表明,α-T抑制滋养体细胞活力(IC50为19.43µg / mL),影响细胞形态,并呈剂量依赖性增加F-actin。α- t处理的变形虫的活性氧生成和RhoA-GTP水平保持正常。研究人员测试了两种影响滋养体细胞骨架组织的抑制剂,一种直接与肌动蛋白细胞松弛素D (CD)相互作用,另一种通过抑制下游效应物Rock Y27632来影响Rho信号通路。Y27632不影响α-T观察到的肌动蛋白聚合的增加,该化合物部分改善了CD对肌动蛋白丝的强烈破坏作用。对接结果表明α-T可能是肌动蛋白中相同相互作用带的CD拮抗剂,但该化合物的作用机制尚需进一步研究。
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来源期刊
CiteScore
2.90
自引率
0.00%
发文量
51
审稿时长
63 days
期刊介绍: The journal provides a medium for rapid publication of investigations of the molecular biology and biochemistry of parasitic protozoa and helminths and their interactions with both the definitive and intermediate host. The main subject areas covered are: • the structure, biosynthesis, degradation, properties and function of DNA, RNA, proteins, lipids, carbohydrates and small molecular-weight substances • intermediary metabolism and bioenergetics • drug target characterization and the mode of action of antiparasitic drugs • molecular and biochemical aspects of membrane structure and function • host-parasite relationships that focus on the parasite, particularly as related to specific parasite molecules. • analysis of genes and genome structure, function and expression • analysis of variation in parasite populations relevant to genetic exchange, pathogenesis, drug and vaccine target characterization, and drug resistance. • parasite protein trafficking, organelle biogenesis, and cellular structure especially with reference to the roles of specific molecules • parasite programmed cell death, development, and cell division at the molecular level.
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