Argentina | info:eu-repo/semantics/article
dc.creatorGaravaglia, Patricia Andrea
dc.creatorRubio, Maria Fernanda
dc.creatorLaverriere, Marc
dc.creatorTasso, Laura Mónica
dc.creatorFichera, Laura Edith
dc.creatorCannata, Joaquin Juan Bautista
dc.creatorGarcia, Gabriela Andrea
dc.date.accessioned2019-10-21T20:11:50Z
dc.date.accessioned2022-10-15T05:15:07Z
dc.date.available2019-10-21T20:11:50Z
dc.date.available2022-10-15T05:15:07Z
dc.date.created2019-10-21T20:11:50Z
dc.date.issued2018-02
dc.identifierGaravaglia, 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.identifier0031-1820
dc.identifierhttp://hdl.handle.net/11336/86738
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4348643
dc.description.abstractSeveral 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.languageeng
dc.publisherCambridge University Press
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.cambridge.org/core/product/identifier/S0031182018000045/type/journal_article
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1017/S0031182018000045
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectChagas disease
dc.subjectchemotherapy
dc.subjectoxido-reductase
dc.subjectregulated cell death
dc.titleTrypanosoma 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.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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