Peroxiredoxins from Trypanosoma cruzi: Virulence factors and drug targets for treatment of Chagas disease?

Piñeyro, María Dolores; Parodi-Talice, Adriana; Arcari, Talia; Robello, Carlos

doi:10.1016/j.gene.2007.10.014

Cited by 73 publications

(75 citation statements)

References 35 publications

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“…The cTcTXNPx polyclonal antiserum immune production was performed as previously described (Nogueira et al 2006). The anti-mTcTXNPx polyclonal antibody was provided by Dr. Carlos Robello (Piñeyro et al 2008).…”

Section: Purification Of Rctctxnpx Recombinant Protein and Productionmentioning

confidence: 99%

Molecular characterization of cytosolic and mitochondrial tryparedoxin peroxidase in Trypanosoma cruzi populations susceptible and resistant to benznidazole

et al. 2008

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Antioxidant defense in Trypanosomatids has been indicated as a potential target for chemotherapy. Tryparedoxin peroxidase (TXNPx) participates in this defense by metabolizing hydrogen peroxide to water molecules. In this work, genes encoding both cytosolic (cTcTXNPx) and mitochondrial (mTcTXNPx) TXNPx were characterized in 15 benznidazole-susceptible and resistant Trypanosoma cruzi strains. Northern blot and real-time RT-PCR analyses revealed that the levels of cTcTXNPx and mTcTXNPx mRNA were two-fold higher in the in-vitro-induced resistant 17 LER T. cruzi population than its drug-susceptible counterpart 17 WTS. The mRNA levels for both genes were similar among the other T. cruzi samples studied. No amplification of these genes was observed in the parasite genome. In silico analyses indicated that cTcTXNPx and mTcTXNPx genes present eight and two copies, respectively, dispersed in the parasite genome. By western blot analysis, anti-cTcTXNPx and anti-mTcTXNPx polyclonal antibodies recognized a 23- and 25-kDa peptide, respectively, in all T. cruzi samples analyzed. The expression levels of these native proteins were similar for all samples except 17 LER, which displayed two-fold greater expression. In addition, the oxidized mTcTXNPx protein (50 kDa) demonstrated 5.5-fold greater expression in the 17 LER population than 17 WTS. Our findings demonstrate increased expression of the cytosolic and mitochondrial TcTXNPx in the T. cruzi population with in-vitro-induced resistance to benznidazole.

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Section: Purification Of Rctctxnpx Recombinant Protein and Productionmentioning

confidence: 99%

Molecular characterization of cytosolic and mitochondrial tryparedoxin peroxidase in Trypanosoma cruzi populations susceptible and resistant to benznidazole

et al. 2008

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“…Parasite lysates were probed by using antibodies against cytosolic (cTXNPx) and mitochondrial (mTXNPx) isoforms of tryparedoxin peroxidase, tryparedoxin isoforms TXN I and TXN II, and iron superoxide dismutase isoforms FeSODa and FeSODb (31,32). Due to the finding of a differential abundance of ␣-tubulin and ␤-actin in T. cruzi isolates (Table 1 and Table 2), we could not use these proteins for normalizing the antioxidant protein content.…”

Section: Resultsmentioning

confidence: 99%

“…5). Others have also documented the differential expression of peroxiredoxin and FeSOD proteins of the antioxidant network in parasites in correlation with in vivo infectivity and pathological behavior (32,34,52). The question arises as to how the TXNPx/TXN antioxidant network is associated with the virulence of the TcI isolates of T. cruzi.…”

Section: Discussionmentioning

confidence: 99%

“…Polyclonal antibodies against T. cruzi cytosolic tryparedoxin peroxidase (cTXNPx) and mitochondrial tryparedoxin peroxidase (mTXNPx) were obtained as described previously (31,32). Polyclonal antibodies against the iron superoxide dismutase (FeSOD) isoforms, FeSODa and FeSODb, and the tryparedoxin isoforms, TXN I and TXN II, were produced as described previously (31,32).…”

Section: Methodsmentioning

confidence: 99%

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TcI Isolates of Trypanosoma cruzi Exploit the Antioxidant Network for Enhanced Intracellular Survival in Macrophages and Virulence in Mice

et al. 2016

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h Trypanosoma cruzi species is categorized into six discrete typing units (TcI to TcVI) of which TcI is most abundantly noted in the sylvatic transmission cycle and considered the major cause of human disease. In our study, the TcI strains Colombiana (COL), SylvioX10/4 (SYL), and a cultured clone (TCC) exhibited different biological behavior in a murine model, ranging from high parasitemia and symptomatic cardiomyopathy (SYL), mild parasitemia and high tissue tropism (COL), to no pathogenicity (TCC). Proteomic profiling of the insect (epimastigote) and infective (trypomastigote) forms by two-dimensional gel electrophoresis/matrix-assisted laser desorption ionization-time of flight mass spectrometry, followed by functional annotation of the differential proteome data sets (>2-fold change, P < 0.05), showed that several proteins involved in (i) cytoskeletal assembly and remodeling, essential for flagellar wave frequency and amplitude and forward motility of the parasite, and (ii) the parasite-specific antioxidant network were enhanced in COL and SYL (versus TCC) trypomastigotes. Western blotting confirmed the enhanced protein levels of cytosolic and mitochondrial tryparedoxin peroxidases and their substrate (tryparedoxin) and iron superoxide dismutase in COL and SYL (versus TCC) trypomastigotes. Further, COL and SYL (but not TCC) were resistant to exogenous treatment with stable oxidants (H 2 O 2 and peroxynitrite [ONOO ؊ ]) and dampened the intracellular superoxide and nitric oxide response in macrophages, and thus these isolates escaped from macrophages. Our findings suggest that protein expression conducive to increase in motility and control of macrophage-derived free radicals provides survival and persistence benefits to TcI isolates of T. cruzi. C hagas disease, caused by the unicellular protozoan Trypanosoma cruzi, is ranked as the third most important parasitic disease in terms of disability-adjusted life years (1, 2). T. cruzi is naturally transmitted by Triatomine insects. In recent years, a significant proportion of the infected population has emigrated from rural areas, leading to the urbanization of Chagas disease in countries where the disease is endemic, as well as internationally (1). Chagas disease is therefore an emergent global public health problem associated with congenital transmission (3, 4), blood transfusions (5), and organ transplantations (6). Current estimates suggest that ϳ70 million people are at risk of infection (7,8) and that ϳ6 million individuals are infected with T. cruzi in Latin America and Mexico. However, these estimates may not be accurate, since they are not derived from detailed epidemiological studies. For example, in Argentina, the Chagas Disease National Control Program reported 13 provinces located in the Central-Northeast area as endemic for Chagas disease in 2010 (9). Vectorial transmission was reported to be absent in Jujuy, Entre Ríos, La Pampa, Neuquén, and Río Negro but active in provinces such as Formosa, Chaco, Córdoba, Santiago del Estero, and others, with a ...

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“…Essa proteína confere proteção a Trypanosoma cruzi contra estresse oxidativo dentro do macrófago (Piacenza et al, 2008) e sua superexpressão aumentou a sobrevivência intracelular do parasita (Piñeyro et al, 2008). A CPX também participa da (Iyer et al, 2008;Romao et al, 2009), e promastigotas de L.(L.) donovani superexpressores de CPX apresentaram maior carga parasitária em macrófagos in vitro (Iyer et al, 2008 comparada a uma cultura recém-iniciada, mais virulenta (Magalhães et al 2014).…”

Section: Triparedoxina Peroxidase Citoplasmáticaunclassified

Análise da participação da oligopeptidase B e triparedoxina peroxidase citoplasmática na virulência de Leishmania (Leishmania) amazonensis.

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Peroxiredoxins from Trypanosoma cruzi: Virulence factors and drug targets for treatment of Chagas disease?

Cited by 73 publications

References 35 publications

Molecular characterization of cytosolic and mitochondrial tryparedoxin peroxidase in Trypanosoma cruzi populations susceptible and resistant to benznidazole

Molecular characterization of cytosolic and mitochondrial tryparedoxin peroxidase in Trypanosoma cruzi populations susceptible and resistant to benznidazole

TcI Isolates of Trypanosoma cruzi Exploit the Antioxidant Network for Enhanced Intracellular Survival in Macrophages and Virulence in Mice

Análise da participação da oligopeptidase B e triparedoxina peroxidase citoplasmática na virulência de <i>Leishmania</i> (<i>Leishmania</i>) <i>amazonensis</i>.

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