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Prostaglandin F2? synthase in Trypanosoma cruzi plays critical roles in oxidative stress and susceptibility to benznidazole.


ABSTRACT: Nifurtimox (Nfx) and benznidazole (Bz) are the current drugs used for the treatment of Chagas disease. The mechanisms of action and resistance to these drugs in this parasite are poorly known. Prostaglandin F2? synthase or old yellow enzyme (OYE), an NAD(P)H flavin oxidoreductase, has been involved in the activation pathway of other trypanocidal drugs such as Nfx; however, its role in the mechanism of action of Bz is uncertain. In this paper, we performed some experiments of functional genomics in the parasite Trypanosoma cruzi with the aim to test the role of this gene in the resistance to Bz. For this, we overexpressed this gene in sensitive parasites and evaluated the resistance level to the drug and other chemical compounds such as hydrogen peroxide, methyl methanesulfonate and gamma radiation. Interestingly, parasites overexpressing OYE showed alteration of enzymes associated with oxidative stress protection such as superoxide dismutase A and trypanothione reductase. Furthermore, transfected parasites were more sensitive to drugs, genetic damage and oxidative stress. Additionally, transfected parasites were less infective than wild-type parasites and they showed higher alteration in mitochondrial membrane potential and cell cycle after treatment with Bz. These results supply essential information to help further the understanding of the mechanism of action of Bz in T. cruzi.

SUBMITTER: Garcia-Huertas P 

PROVIDER: S-EPMC5627119 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Prostaglandin F2α synthase in <i>Trypanosoma cruzi</i> plays critical roles in oxidative stress and susceptibility to benznidazole.

García-Huertas Paola P   Mejía-Jaramillo Ana María AM   Machado Carlos Renato CR   Guimarães Anna Cláudia AC   Triana-Chávez Omar O  

Royal Society open science 20170920 9


Nifurtimox (Nfx) and benznidazole (Bz) are the current drugs used for the treatment of Chagas disease. The mechanisms of action and resistance to these drugs in this parasite are poorly known. Prostaglandin F2α synthase or old yellow enzyme (OYE), an NAD(P)H flavin oxidoreductase, has been involved in the activation pathway of other trypanocidal drugs such as Nfx; however, its role in the mechanism of action of Bz is uncertain. In this paper, we performed some experiments of functional genomics  ...[more]

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