Buchumschlag

New Insights into the Role of the Trypanosoma cruzi Aldo-Keto Reductase TcAKR

Chagas disease is a zoonotic infectious disease caused by the protozoan parasite Trypanosoma cruzi. It is distributed worldwide, affecting around 7 million people; there is no effective treatment, and it constitutes a leading cause of disability and premature death in the Americas. Only two drugs ar...

Ausführliche Beschreibung

Gespeichert in:
1. Verfasser: Díaz-Viraqué, Florencia (author)
Weitere Verfasser: Chiribao, María Laura (author), Paes-Vieira, Lisvane (author), Machado, Matias R. (author), Faral-Tello, Paula (author), Tomasina, Ramiro (author), Trochine, Andrea (author), Robello, Carlos (author)
Format: article
Sprache:Englisch
Veröffentlicht: 2023
Schlagworte:
Trypanosoma cruzi
Aldo-keto reductase
Mitochondrial enzyme
Kinetoplast
Prostaglandin F2α synthase
Nifurtimox metabolism
Ciencias Médicas y de la Salud
Ciencias de la Salud
Parasitología
Online-Zugang:https://hdl.handle.net/20.500.12381/3247
https://doi.org/10.3390/pathogens12010085
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Zusammenfassung:Chagas disease is a zoonotic infectious disease caused by the protozoan parasite Trypanosoma cruzi. It is distributed worldwide, affecting around 7 million people; there is no effective treatment, and it constitutes a leading cause of disability and premature death in the Americas. Only two drugs are currently approved for the treatment, Benznidazole and Nifurtimox, and both have to be activated by reducing the nitro-group. The T. cruzi aldo-keto reductase (TcAKR) has been related to the metabolism of benznidazole. TcAKR has been extensively studied, being most efforts focused on characterizing its implication in trypanocidal drug metabolism; however, little is known regarding its biological role. Here, we found that TcAKR is confined, throughout the entire life cycle, into the parasite mitochondria providing new insights into its biological function. In particular, in epimastigotes, TcAKR is associated with the kinetoplast, which suggests additional roles of the protein. The upregulation of TcAKR, which does not affect TcOYE expression, was correlated with an increase in PGF2α, suggesting that this enzyme is related to PGF2α synthesis in T. cruzi. Structural analysis showed that TcAKR contains a catalytic tetrad conserved in the AKR superfamily. Finally, we found that TcAKR is also involved in Nfx metabolization.

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