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https://www.arca.fiocruz.br/handle/icict/12608
MOLECULAR CHARACTERIZATION OF CYCLOPHILIN (TCCYP19) IN TRYPANOSOMA CRUZI POPULATIONS SUSCEPTIBLE AND RESISTANT TO BENZNIDAZOLE
Author
Affilliation
Universidade Federal do Piauí. Floriano, PI, Brasil/Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil/Universidade Federal do Ceará. Instituto de Ciências do Mar. Fortaleza, CE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia. Belo Horizonte, MG, Brasil
Universidade Federal do Piauí. Teresina, PI, Brasil
Universidade Federal do Piauí. Floriano, PI, Brasil
Universidade Federal do Piauí. Teresina, PI, Brasil
Instituto Nacional de Parasitología “Dr. M. Fatala Chabén”. Buenos Aires, AG
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia. Belo Horizonte, MG, Brasil
Universidade Federal do Ceará. Instituto de Ciências do Mar. Fortaleza, CE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia. Belo Horizonte, MG, Brasil
Universidade Federal do Piauí. Teresina, PI, Brasil
Universidade Federal do Piauí. Floriano, PI, Brasil
Universidade Federal do Piauí. Teresina, PI, Brasil
Instituto Nacional de Parasitología “Dr. M. Fatala Chabén”. Buenos Aires, AG
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia. Belo Horizonte, MG, Brasil
Universidade Federal do Ceará. Instituto de Ciências do Mar. Fortaleza, CE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia. Belo Horizonte, MG, Brasil
Abstract
Cyclophilin (TcCyP19), a peptidyl-prolyl cis/trans isomerase, is a keymolecule with diverse biological functions that include roles in molecular chaperoning, stress response, immune modulation, and signal transduction. In this respect, TcCyP19 could serve as a potential drug target in disease-causing parasites. Previous studies employing proteomics techniques have shown that the TcCyP19 isoform was more abundant in a benznidazole (BZ)-resistant Trypanosoma cruzi population than in its susceptible counterpart. In this study, TcCyP19 has been characterized in BZ-susceptible and BZ-resistant T. cruzi populations. Phylogenetic analysis revealed a clear dichotomy between Cyphophilin A (CyPA) sequences from trypanosomatids and mammals. Sequencing analysis revealed that the amino acid sequences of TcCyP19 were identical among the T. cruzi samples analyzed. Southern blot analysis showed that TcCyP19 is a singlecopy gene, located in chromosomal bands varying in size from 0.68 to 2.2 Mb, depending on the strain of T. cruzi. Northern blot and qPCR indicated that the levels of TcCyP19mRNA were twofold higher in drugresistant T. cruzi populations than in their drug-susceptible counterparts. Similarly, as determined by twodimensional gel electrophoresis immunoblot, the expression of TcCyP19 protein was increased to the same degree in BZ-resistant T. cruzi populations. No differences in TcCyP19 mRNA and protein expression levels were observed between the susceptible and the naturally resistant T. cruzi strains analyzed. Taken together, these data indicate that cyclophilin TcCyP19 expression is up-regulated at both transcriptional and translational levels in T. cruzi populations that were in vitro-induced and in vivoselected for resistance to BZ.
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