Dehydroepiandrosterone Effect on Toxoplasma gondii: Molecular Mechanisms Associated to Parasite Death

Microorganisms

Lenin Domínguez-Ramírez¹  CarmenT. Gómez-De León²  Jorge Morales-Montor²  Pedro Ostoa-Saloma²  OlgaA. Patrón-Soberano³  KarenE. Nava-Castro⁴  Saé Muñiz-Hernández⁵  Angélica Luna-Nophal⁵ 

[1] Departamento de Ciencias Químico-Biológicas, Escuela de Ciencias, Universidad de las Américas Puebla, Santa Catarina Mártir, Cholula, Puebla 72810, Mexico;Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Ciudad de México 04510, Mexico;División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, Camino a la Presa San José 2055, Col. Lomas 4a. sección, San Luis Potosí 78216, Mexico;Laboratorio de Genotoxicología y Mutagénesis Ambientales, Departamento de Ciencias Ambientales, Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico;Laboratorio de Oncología Experimental, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Secretaria de Salud, Ciudad de México 14080, Mexico;

关键词: Toxoplasmosis;    Toxoplasma gondii;    tachyzoite;    antiparasitic effect;    dehydroepiandrosterone;    DHEA;   

DOI  :  10.3390/microorganisms9030513

来源: DOAJ

【 摘 要 】

Toxoplasmosis is a zoonotic disease caused by the apicomplexa protozoan parasite Toxoplasma gondii. This disease is a health burden, mainly in pregnant women and immunocompromised individuals. Dehydroepiandrosterone (DHEA) has proved to be an important molecule that could drive resistance against a variety of infections, including intracellular parasites such as Plasmodium falciparum and Trypanozoma cruzi, among others. However, to date, the role of DHEA on T. gondii has not been explored. Here, we demonstrated for the first time the toxoplasmicidal effect of DHEA on extracellular tachyzoites. Ultrastructural analysis of treated parasites showed that DHEA alters the cytoskeleton structures, leading to the loss of the organelle structure and organization as well as the loss of the cellular shape. In vitro treatment with DHEA reduces the viability of extracellular tachyzoites and the passive invasion process. Two-dimensional (2D) SDS-PAGE analysis revealed that in the presence of the hormone, a progesterone receptor membrane component (PGRMC) with a cytochrome b5 family heme/steroid binding domain-containing protein was expressed, while the expression of proteins that are essential for motility and virulence was highly reduced. Finally, in vivo DHEA treatment induced a reduction of parasitic load in male, but not in female mice.

【 授权许可】

Unknown