1. The effects of endoplasmic reticulum stressors, tunicamycin and dithiothreitol on Trypanosoma cruzi.
- Author
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Messias Sandes J, Nascimento Moura DM, Divina da Silva Santiago M, Barbosa de Lima G, Cabral Filho PE, da Cunha Gonçalves de Albuquerque S, de Paiva Cavalcanti M, Fontes A, and Bressan Queiroz Figueiredo RC
- Subjects
- Calreticulin genetics, Calreticulin metabolism, Endoplasmic Reticulum drug effects, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum Chaperone BiP, Endoplasmic Reticulum Stress drug effects, Endoplasmic Reticulum Stress genetics, Gene Expression Regulation drug effects, Heat-Shock Proteins genetics, Heat-Shock Proteins metabolism, Parasitic Sensitivity Tests, Trypanosoma cruzi genetics, Trypanosoma cruzi growth & development, Trypanosoma cruzi ultrastructure, Unfolded Protein Response drug effects, Unfolded Protein Response genetics, Dithiothreitol pharmacology, Trypanosoma cruzi drug effects, Tunicamycin pharmacology
- Abstract
In higher eukaryotic cells, pertubations in ER environment, called ER stress, usually activate unfolded protein response (UPR) pathway in an attempt to re-stablish the ER homeostasis and prevent cell death. Because trypanosomatids appear to lack the classical UPR, it is not clear how these parasites respond to ER stress. Thus, the aim of this work was to evaluate the effects of ER stressors tunicamycin (TM) or dithiothreitol (DTT) on Trypanosoma cruzi. The TM treatment showed strong trypanostatic effect. At 2.5 μg/mL of TM, the mRNA levels of both binding protein (BiP) and calreticulin (CRT) increased significantly, whereas the protein levels of BiP remained stable. TM treatment induced ultrastructural changes compatible with an autophagic process. The DTT treatment inhibited the cell growth, induced drastic morphological changes, mitochondrial membrane depolarization and increased ROS production. The expression of BiP apparently was not affected by DTT, whereas the mRNA levels of BiP and CRT were significantly reduced. Our results suggest that TM induces autophagy/ER-phagy without causing substantial injury to the parasite. Conversely, the DTT treatment seems to rupture the mitochondrion homeostasis leading to parasite death. The comprehension of the mechanisms behind the susceptibility of T. cruzi to ER stress open perspectives for the development of chemotherapeutic agents addressed to these pathways., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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