Argentina
| info:eu-repo/semantics/article
Trypanosoma cruzi: Death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
dc.creator | Garavaglia, Patricia Andrea | |
dc.creator | Rubio, Maria Fernanda | |
dc.creator | Laverriere, Marc | |
dc.creator | Tasso, Laura Mónica | |
dc.creator | Fichera, Laura Edith | |
dc.creator | Cannata, Joaquin Juan Bautista | |
dc.creator | Garcia, Gabriela Andrea | |
dc.date.accessioned | 2019-10-21T20:11:50Z | |
dc.date.accessioned | 2022-10-15T05:15:07Z | |
dc.date.available | 2019-10-21T20:11:50Z | |
dc.date.available | 2022-10-15T05:15:07Z | |
dc.date.created | 2019-10-21T20:11:50Z | |
dc.date.issued | 2018-02 | |
dc.identifier | Garavaglia, Patricia Andrea; Rubio, Maria Fernanda; Laverriere, Marc; Tasso, Laura Mónica; Fichera, Laura Edith; et al.; Trypanosoma cruzi: Death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone; Cambridge University Press; Parasitology; 145; 9; 2-2018; 1251-1259 | |
dc.identifier | 0031-1820 | |
dc.identifier | http://hdl.handle.net/11336/86738 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4348643 | |
dc.description.abstract | Several ortho-naphthoquinones (o-NQs) have trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (TcAKR) reduces o-NQs, such as β-lapachone (β-Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of TcAKR activity and expression in two T. cruzi strains, CL Brener and Nicaragua, showed that TcAKR expression is 2.2-fold higher in CL Brener than in Nicaragua. Here, we studied the trypanocidal effect and induction of several death phenotypes by β-Lap and 9,10-PQ in epimastigotes of these two strains. The CL Brener strain was more resistant to both o-NQs than Nicaragua, indicating that greater TcAKR activity is unlikely to be a major influence on o-NQ toxicity. Evaluation of changes in ROS production, mitochondrial membrane potential, phosphatidylserine exposure and monodansylcadaverine labelling evidenced that β-Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and T. cruzi strain analysed. To study whether TcAKR participates in o-NQ activation in intact parasites, β-Lap and 9,10-PQ trypanocidal effect was next evaluated in TcAKR-overexpressing parasites. Only β-Lap was more effective and induced greater ROS production in TcAKR-overexpressing epimastigotes than in controls, suggesting that TcAKR may participate in β-Lap activation. | |
dc.language | eng | |
dc.publisher | Cambridge University Press | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://www.cambridge.org/core/product/identifier/S0031182018000045/type/journal_article | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1017/S0031182018000045 | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/restrictedAccess | |
dc.subject | Chagas disease | |
dc.subject | chemotherapy | |
dc.subject | oxido-reductase | |
dc.subject | regulated cell death | |
dc.title | Trypanosoma cruzi: Death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion |