Patolsky Rocío G, Laiolo Jerónimo, Díaz-Pérez Luciano, Luna Pizarro Gabriel, Mayol Gonzalo F, Touz María C, Feliziani Constanza, Rópolo Andrea S
Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina.
Universidad Católica de Córdoba, Córdoba, Argentina.
Front Microbiol. 2025 Jan 3;15:1513053. doi: 10.3389/fmicb.2024.1513053. eCollection 2024.
Post-translational modifications of proteins provide cellular physiology with a broad range of adaptability to the external environment flexibly and rapidly. In the case of the protozoan parasite , the study of these modifications has gained relevance in recent years, mainly focusing on methylation and deacetylation of proteins. This study investigates the significance of acetylation in this protozoan parasite.
This study explores the role of acetylation in through a combination of immunofluorescence assays, manipulation of acetyltransferase enzymes, and the use of garcinol, an acetylation inhibitor, during the growth phase.
The acetylation of histone marks H3K9 and H3K27 occurs during growth and is followed by deacetylation during encystation. Transfections modifying acetyltransferase activity induced a latent cellular state, underscoring the importance of protein acetylation for parasite survival. Garcinol treatment during growth caused significant morphological changes, including plasma membrane blebbing and apoptotic-like bodies. Immunofluorescence revealed these bodies contained α-tubulin/acetylated α-tubulin and reactive oxygen species. Flow cytometry and Annexin V staining indicated early apoptosis within 24 hours of treatment. Additionally, garcinol led to the deacetylation of H3K9 and H3K27, with redistribution of tubulin and acetylated tubulin from microtubules to the cytosol. Significantly, garcinol prevented parasite recrudescence after treatment withdrawal.
These results demonstrate that acetylation is essential for trophozoite survival and highlight the natural histone acetyltransferase inhibitor garcinol as a potential candidate for drug development against giardiasis, considering its giardicidal activity.
蛋白质的翻译后修饰为细胞生理学提供了广泛的适应性，使其能够灵活快速地应对外部环境。就原生动物寄生虫而言，近年来对这些修饰的研究变得愈发重要，主要集中在蛋白质的甲基化和去乙酰化方面。本研究旨在探讨乙酰化在这种原生动物寄生虫中的意义。
本研究通过免疫荧光测定、乙酰转移酶的操作以及在生长阶段使用乙酰化抑制剂藤黄菌素相结合的方法，探究乙酰化在[此处原文缺失具体研究对象]中的作用。
组蛋白标记H3K9和H3K27的乙酰化在生长过程中发生，随后在包囊形成过程中发生去乙酰化。改变乙酰转移酶活性的转染诱导了一种潜伏的细胞状态，凸显了蛋白质乙酰化对寄生虫生存的重要性。生长期间用藤黄菌素处理导致显著的形态变化，包括质膜起泡和凋亡样小体。免疫荧光显示这些小体含有α - 微管蛋白/乙酰化α - 微管蛋白和活性氧物质。流式细胞术和膜联蛋白V染色表明处理后24小时内出现早期凋亡。此外，藤黄菌素导致H3K9和H3K27去乙酰化，微管蛋白和乙酰化微管蛋白从微管重新分布到细胞质中。值得注意的是，藤黄菌素在撤药后可防止寄生虫复发。
这些结果表明乙酰化对滋养体生存至关重要，并突出了天然组蛋白乙酰转移酶抑制剂藤黄菌素作为抗贾第虫病药物开发的潜在候选物，考虑到其杀贾第虫活性。
