Redox metabolism in Trypanosoma cruzi: Functional characterization of tryparedoxins revisited

Arias, Diego Gustavo; Márquez, Vanina Elizabet; Chiribao, María Laura; Gadelha, Fernanda Ramos; Robello, Carlos; Iglesias, Alberto A.; Guerrero, Sandra

doi:10.1016/j.freeradbiomed.2013.04.036

Cited by 37 publications

(24 citation statements)

References 62 publications

(111 reference statements)

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“…However, when 2-Cys peroxiredoxins were replaced by GSSG or GSNO as final acceptor in the coupled assay, TcTXNIIC45SΔ22C exhibited identical catalytic efficiency to TcTXNIIΔ22C. These results indicate that reduced TcTXNIIC45SΔ22C [plus T(SH) 2 ] exhibited a capacity to reduce low molecular mass disulfides via monothiol mechanism (similar to monothiol glutaredoxins [15,20,21]). This result was consistent with the formation of adducts between low molecular mass disulfides with monothiolic TXNII version (TcTXNIIC45SΔ22C, Fig.…”

Section: Resultsmentioning

confidence: 92%

“…We tested the ability of TcTXNIIC45SΔ22C to catalyze the reduction of T. cruzi peroxiredoxins (cTXNPx or mTXNPx) by T(SH) 2 . This was evaluated by the coupled assay for trypanothione-dependent t-bOOH reduction via a tryparedoxin/peroxidase-mediated reaction [15]. As positive control, TcTXNIIΔ22C was used in equivalent conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Fidelity and correctness of the gen was confirmed on both strands by complete sequencing (Macrogen, South Korea). The recombinant protein was obtained as N-terminal hexahistidine-tag protein from E. coli BL21 (DE3) culture and purified in a Ni 2+ -Hi-Trap resin column under identical conditions as described by Arias and co-workers [15]. Pure protein was stored at −80°C in 20 mM Tris-HCl, pH 7.5; and 1 mM EDTA and 5% (v/v) glycerol.…”

Section: Generation Of Tctxniic45s By Site-directed Mutagenesis Overmentioning

confidence: 99%

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Molecular characterization and interactome analysis of Trypanosoma cruzi tryparedoxin II

Arias

Piñeyro

Iglesias

et al. 2015

Journal of Proteomics

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Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Generation Of Tctxniic45s By Site-directed Mutagenesis Overmentioning

confidence: 99%

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Molecular characterization and interactome analysis of Trypanosoma cruzi tryparedoxin II

Arias

Piñeyro

Iglesias

et al. 2015

Journal of Proteomics

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“…The increase in tryparedoxin perdoxidases occurred in infective trypomastigote and replicative amastigote stages irrespective of the cell types (e.g., muscle cells in this study, and LLC-MK2 and macrophages in other studies [34,50]) used for culturing the parasites. Regeneration of the reduced TXNPx depends on cytosolic (TXN I)-and membrane (TXN II)-localized thioredoxin substrates (31,51). Consistent with the increased abundance of TXNPx, the TXN I level was also increased in COL and SYL trypomastigotes (Fig.…”

Section: Discussionmentioning

confidence: 54%

“…The MS peak filtering included the indicated parametersmass range, 800 to 4,000 Da; minimum signal-to-noise ratio (S/N) filter, 10; mass exclusion list tolerance, 0.5 Da-and the mass exclusion list for some trypsin and keratin-containing compounds included masses of 842. 51 The expectation value is the number of matches with equal or better scores that are expected to occur by chance alone. The default significance threshold is P Ͻ 0.05; however, we used a stringent threshold of 10 Ϫ3 for protein identification: the lower the expectation value, the more significant the score.…”

Section: Methodsmentioning

confidence: 99%

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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Polyamine-based thiols in pathogens

Comini

2022

Redox Chemistry and Biology of Thiols

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Redox metabolism in Trypanosoma cruzi: Functional characterization of tryparedoxins revisited

Cited by 37 publications

References 62 publications

Molecular characterization and interactome analysis of Trypanosoma cruzi tryparedoxin II

Molecular characterization and interactome analysis of Trypanosoma cruzi tryparedoxin II

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

Polyamine-based thiols in pathogens

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