Programa Biología Celular y Molecular, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile.
Oxid Med Cell Longev. 2020 Dec 10;2020:8867701. doi: 10.1155/2020/8867701. eCollection 2020.
Chagas disease is a neglected tropical disease, which affects an estimate of 6-7 million people worldwide. Chagas disease is caused by , which is a eukaryotic flagellate unicellular organism. At the primary infection sites, these parasites are phagocytized by macrophages, which produce reactive oxygen species (ROS) in response to the infection with . The ROS produce damage to the host tissues; however, macrophage-produced ROS is also used as a signal for proliferation. At the later stages of infection, mitochondrial ROS is produced by the infected cardiomyocytes that contribute to the oxidative damage, which persists at the chronic stage of the disease. The oxidative damage leads to a functional impairment of the heart. In this review article, we will discuss the mechanisms by which is able to deal with the oxidative stress and how this helps the parasite growth at the acute phase of infection and how the oxidative stress affects the cardiomyopathy at the chronic stage of the Chagas disease. We will describe the mechanisms used by the parasite to deal with ROS and reactive nitrogen species (RNS) through the trypanothione and the mechanisms used to repair the damaged DNA. Also, a description of the events produced by ROS at the acute and chronic stages of the disease is presented. Lastly, we discuss the benefits of ROS for growth and proliferation and the possible mechanisms involved in this phenomenon. Hypothesis is put forward to explain the molecular mechanisms by which ROS triggers parasite growth and proliferation and how ROS is able to produce a long persisting damage on cardiomyocytes even in the absence of the parasite.
恰加斯病是一种被忽视的热带病，估计影响全球 600 至 700 万人。恰加斯病是由克氏锥虫引起的，它是一种真核鞭毛单细胞生物。在初次感染部位，这些寄生虫被巨噬细胞吞噬，巨噬细胞会产生活性氧物质（ROS）来应对感染。ROS 会对宿主组织造成损伤，但巨噬细胞产生的 ROS 也被用作寄生虫增殖的信号。在感染后期，被感染的心肌细胞会产生线粒体 ROS，这有助于氧化损伤，这种损伤在疾病的慢性阶段持续存在。氧化损伤导致心脏功能障碍。在这篇综述文章中，我们将讨论克氏锥虫应对氧化应激的机制，以及这种机制如何帮助寄生虫在感染的急性期生长，以及氧化应激如何影响恰加斯病的慢性阶段的心肌病。我们将描述寄生虫通过硫代葡萄糖苷和 DNA 修复机制来应对 ROS 和活性氮物质（RNS）的机制。还描述了在疾病的急性期和慢性期产生的 ROS 事件。最后，我们讨论了 ROS 对寄生虫生长和增殖的益处以及涉及这种现象的可能机制。提出了一个假设来解释 ROS 触发寄生虫生长和增殖的分子机制，以及 ROS 如何在没有寄生虫的情况下对心肌细胞产生长期持续的损伤。
