3-溴丙酮酸损害克氏锥虫线粒体功能。

IF 3.3 3区 医学 Q2 MICROBIOLOGY
Rafaella Oliveira da Costa, Davi Barreto-Campos, Juliana Barbosa-de-Barros, Giovanna Frechiani, Luiz Fernando Carvalho-Kelly, Ayra Diandra Carvalho-de-Araújo, José Roberto Meyer-Fernandes, Claudia Fernanda Dick
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引用次数: 0

摘要

克氏锥虫是一种动质体寄生虫,是恰加斯病的病原。鉴于这种寄生虫病的发病率和死亡率很高,需要研究可能的替代治疗方法。3-溴丙酮酸(3-BrPA)是丙酮酸的合成类似物,在21世纪初作为抗癌剂被引入,影响某些微生物的增殖和运动。因此,本研究旨在评估3-BrPA在克氏体能量代谢、增殖和感染性中的作用,主要关注线粒体状态、ATP产生和关键的糖酵解途径酶。与对照细胞相比,3-BrPA细胞的线粒体功能受损。因此,维持在对照条件下的细胞比维持在3-BrPA条件下的细胞具有更高的细胞内ATP含量和更高的外磷酸酶活性。然而,3-BrPA降低了外核酸酶的活性,并能够水解5'-AMP、ADP和ATP。当我们评估两个关键的糖酵解途径酶,葡萄糖激酶(GK)和甘油醛-3-磷酸脱氢酶(GAPDH)时,我们观察到3-BrPA诱导GAPDH活性升高,但不改变GK活性。克氏锥虫的代偿能量机制可能影响细胞代谢过程,从而影响功能性感染过程,提示3-BrPA在未来恰加斯病的临床应用中具有潜在的应用价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
3-Bromopyruvate Impairs Mitochondrial Function in Trypanosoma cruzi.

Trypanosoma cruzi is a kinetoplastid parasite and etiological agent of Chagas disease. Given the significant morbidity and mortality rates of this parasitic disease, possible treatment alternatives need to be studied. 3-Bromopyruvate (3-BrPA) is a synthetic analog of pyruvate that was introduced in the early 21st century as an anticancer agent, affecting the proliferation and motility of certain microorganisms. Therefore, this work aims to evaluate the role of 3-BrPA in the energy metabolism, proliferation, and infectivity of T. cruzi, with a primary focus on the mitochondrial state, ATP production, and the key glycolytic pathway enzymes. It was observed that mitochondrial function in 3-BrPA cells was impaired compared to control cells. Accordingly, cells maintained in control conditions have a higher intracellular ATP content than cells maintained with 3-BrPA and higher ecto-phosphatase activity. However, the 3-BrPA reduced ecto-nuclease activity and was capable of hydrolyzing 5'-AMP, ADP, and ATP. When we evaluated two key glycolytic pathway enzymes, glucose kinase (GK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we observed that 3-BrPA induced higher GAPDH activity but did not alter GK activity. The compensatory energy mechanisms presented in T. cruzi may influence the process of cell metabolism and, consequently, the functional infectious process, suggesting the potential use of 3-BrPA in future clinical applications for Chagas disease.

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来源期刊
Pathogens
Pathogens Medicine-Immunology and Allergy
CiteScore
6.40
自引率
8.10%
发文量
1285
审稿时长
17.75 days
期刊介绍: Pathogens (ISSN 2076-0817) publishes reviews, regular research papers and short notes on all aspects of pathogens and pathogen-host interactions. There is no restriction on the length of the papers. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible. Full experimental and/or methodical details must be provided for research articles.
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