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The level of ascorbate peroxidase is enhanced in benznidazole-resistant populations of Trypanosoma cruzi and its expression is modulated by stress generated by hydrogen peroxide
Nogueira, Fernanda Barbosa; Rodrigues, Joyce Fernanda A; Correa, Marcos Messias S; Ruiz, Jerônimo Conceição; Romanha, Alvaro José; Murta, Silvane Maria Fonseca.
  • Nogueira, Fernanda Barbosa; Fiocruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte. BR
  • Rodrigues, Joyce Fernanda A; Fiocruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte. BR
  • Correa, Marcos Messias S; Fiocruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte. BR
  • Ruiz, Jerônimo Conceição; Fiocruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte. BR
  • Romanha, Alvaro José; Fiocruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte. BR
  • Murta, Silvane Maria Fonseca; Fiocruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte. BR
Mem. Inst. Oswaldo Cruz ; 107(4): 494-502, June 2012. ilus
Article in English | LILACS | ID: lil-626443
ABSTRACT
Ascorbate peroxidases (APX) are class I heme-containing enzymes that convert hydrogen peroxide into water molecules. The gene encoding APX has been characterized in 11 strains of Trypanosoma cruzi that are sensitive or resistant to benznidazole (BZ). Bioinformatic analysis revealed the presence of two complete copies of the T. cruzi APX (TcAPX) gene in the genome of the parasite, while karyotype analysis showed that the gene was present in the 2.000-kb chromosome of all of the strains analyzed. The sequence of TcAPX exhibited greater levels of similarity to those of orthologous enzymes from Leishmania spp than to APXs from the higher plant Arabidopsis thaliana. Northern blot and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed no significant differences in TcAPX mRNA levels between the T. cruzi strains analyzed. On the other hand, Western blots showed that the expression levels of TcAPX protein were, respectively, two and three-fold higher in T. cruzi populations with in vitro induced (17 LER) and in vivo selected (BZR) resistance to BZ, in comparison with their corresponding susceptible counterparts. Moreover, the two BZ-resistant populations exhibited higher tolerances to exogenous hydrogen peroxide than their susceptible counterparts and showed TcAPX levels that increased in a dose-dependent manner following exposure to 100 and 200 µM hydrogen peroxide.
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Full text: Available Index: LILACS (Americas) Main subject: Trypanocidal Agents / Trypanosoma cruzi / Drug Resistance / Ascorbate Peroxidases / Hydrogen Peroxide / Nitroimidazoles Language: English Journal: Mem. Inst. Oswaldo Cruz Journal subject: Tropical Medicine / Parasitology Year: 2012 Type: Article Affiliation country: Brazil Institution/Affiliation country: Fiocruz/BR

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Full text: Available Index: LILACS (Americas) Main subject: Trypanocidal Agents / Trypanosoma cruzi / Drug Resistance / Ascorbate Peroxidases / Hydrogen Peroxide / Nitroimidazoles Language: English Journal: Mem. Inst. Oswaldo Cruz Journal subject: Tropical Medicine / Parasitology Year: 2012 Type: Article Affiliation country: Brazil Institution/Affiliation country: Fiocruz/BR