The Role of Heme and Reactive Oxygen Species in Proliferation and Survival of<i>Trypanosoma cruzi</i>

Paes, Márcia Cristina; Cosentino-Gomes, Daniela; Souza, Cintia Fernandes; Nogueira, Natália Pereira de Almeida; Meyer‐Fernandes, José Roberto

doi:10.1155/2011/174614

Cited by 25 publications

(18 citation statements)

References 80 publications

(99 reference statements)

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“…Thioredoxin reductase is an antioxidant enzyme that promotes the conversion of oxidized thioredoxin and can act together with the glutathione system to regenerate reduced glutathione, contributing to the detoxification of free radicals and impairing oxidative stress in hematophagous insects [20]. According to Paes et al [21], low concentrations of molecules involved in oxidative stress promote the proliferation of T. cruzi . Therefore, the expression of thioredoxin reductase in infected bugs may be modulated by T. cruzi to allow parasite proliferation inside the T. infestans midgut.…”

Section: Resultsmentioning

confidence: 99%

Differential Expression Profiles in the Midgut of Triatoma infestans Infected with Trypanosoma cruzi

et al. 2013

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Chagas disease, or American trypanosomiasis, is a parasitic disease caused by the protozoan Trypanosoma cruzi and is transmitted by insects from the Triatominae subfamily. To identify components involved in the protozoan-vector relationship, we constructed and analyzed cDNA libraries from RNA isolated from the midguts of uninfected and T. cruzi-infected Triatoma infestans, which are major vectors of Chagas disease. We generated approximately 440 high-quality Expressed Sequence Tags (ESTs) from each T. infestans midgut cDNA library. The sequences were grouped in 380 clusters, representing an average length of 664.78 base pairs (bp). Many clusters were not classified functionally, representing unknown transcripts. Several transcripts involved in different processes (e.g., detoxification) showed differential expression in response to T. cruzi infection. Lysozyme, cathepsin D, a nitrophorin-like protein and a putative 14 kDa protein were significantly upregulated upon infection, whereas thioredoxin reductase was downregulated. In addition, we identified several transcripts related to metabolic processes or immunity with unchanged expressions, including infestin, lipocalins and defensins. We also detected ESTs encoding juvenile hormone binding protein (JHBP), which seems to be involved in insect development and could be a target in control strategies for the vector. This work demonstrates differential gene expression upon T. cruzi infection in the midgut of T. infestans. These data expand the current knowledge regarding vector-parasite interactions for Chagas disease.

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Section: Resultsmentioning

confidence: 99%

Differential Expression Profiles in the Midgut of Triatoma infestans Infected with Trypanosoma cruzi

et al. 2013

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“…Regardless of being necessary as cofactor for several biological processes in the parasite (17), heme has cytotoxic action due to the generation of reactive oxygen species (ROS) (18). Even though most ROS are a consequence of cellular respiration, xenobiotics present an important source of oxidative stress, either releasing ROS by biotransformation or via direct consumption of antioxidant defenses (19). In addition, stress-inducing agents are able to affect sphingolipid metabolism, resulting in the accumulation of ceramides (20), which is a sphingolipid comprised of a sphingosine-related base linked to a fatty acid through an amide bond.…”

Section: Introductionmentioning

confidence: 99%

Thiol efflux mediated by an ABCC-like transporter participates forTrypanosoma cruziadaptation to environmental and chemotherapeutic stresses

Costa

et al. 2020

Preprint

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The protozoan Trypanosoma cruzi is the etiologic agent for Chagas disease, which affects 6-7 million people worldwide. The parasite presents high biological diversity, reflecting on the inefficiency of benznidazole in chronic or older patients. ABC superfamily proteins contain active transporters involved in the xenobiotic and endobiotic efflux and overexpressed in MDR cells. An ABCC-like transport was identified in the T. cruzi Y strain, being able to extrude thiol-conjugated compounds. As non-protein thiols represent prime line of defense towards reactive species, ABCC-like activity could participate in the regulation of mediators implicated in responses to cellular stress arising from a variety of stimuli, as environmental or chemotherapeutic. This study shows that T. cruzi ABCC-like protein transports GSH, GSSG and ceramides, all implicated in cellular stress. Hemin, representative from the hematophagous feeding of the vector, was transported as well, suggesting a role for ABCC as a metal-thiol transporter. In addition, all strains evaluated showed ABCC-like activity, while no ABCB1-like activity was detected. Also, results suggest that ABCC-like does not associate to natural resistance to benznidazole, considering that the sensitive strains CL Brener and Berenice showed higher ABCC-like activity than the resistant strains Y and Colombiana. Instead, ABCC-like efflux increased after continuous exposure of Y strain to benznidazole. Moreover, ABCC does not perform direct efflux of drug and its participation in the machinery of protection against stress depends on the efflux of metabolites in conjugation to or in cotransport with thiol.

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“…Later, the parasite escapes from its vacuole into the cytosol, which may also represent a source of oxidative stress via the generation of ROS due to electron leakage from mitochondrial respiratory complexes [15], [18]. In the triatomine, the parasite develops inside the gut, where it is confronted with several changes, such as temperature, osmolality, nutrient supply, acidic or alkaline pH, as well as the oxidative stress caused by ROS production through hemoglobin degradation and nitrogen intermediate production by host defense mechanisms [13], [19], [20].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress and DNA Lesions: The Role of 8-Oxoguanine Lesions in Trypanosoma cruzi Cell Viability

et al. 2013

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The main consequence of oxidative stress is the formation of DNA lesions, which can result in genomic instability and lead to cell death. Guanine is the base that is most susceptible to oxidation, due to its low redox potential, and 8-oxoguanine (8-oxoG) is the most common lesion. These characteristics make 8-oxoG a good cellular biomarker to indicate the extent of oxidative stress. If not repaired, 8-oxoG can pair with adenine and cause a G:C to T:A transversion. When 8-oxoG is inserted during DNA replication, it could generate double-strand breaks, which makes this lesion particularly deleterious. Trypanosoma cruzi needs to address various oxidative stress situations, such as the mammalian intracellular environment and the triatomine insect gut where it replicates. We focused on the MutT enzyme, which is responsible for removing 8-oxoG from the nucleotide pool. To investigate the importance of 8-oxoG during parasite infection of mammalian cells, we characterized the MutT gene in T. cruzi (TcMTH) and generated T. cruzi parasites heterologously expressing Escherichia coli MutT or overexpressing the TcMTH enzyme. In the epimastigote form, the recombinant and wild-type parasites displayed similar growth in normal conditions, but the MutT-expressing cells were more resistant to hydrogen peroxide treatment. The recombinant parasite also displayed significantly increased growth after 48 hours of infection in fibroblasts and macrophages when compared to wild-type cells, as well as increased parasitemia in Swiss mice. In addition, we demonstrated, using western blotting experiments, that MutT heterologous expression can influence the parasite antioxidant enzyme protein levels. These results indicate the importance of the 8-oxoG repair system for cell viability.

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The Role of Heme and Reactive Oxygen Species in Proliferation and Survival ofTrypanosoma cruzi

Cited by 25 publications

References 80 publications

Differential Expression Profiles in the Midgut of Triatoma infestans Infected with Trypanosoma cruzi

Differential Expression Profiles in the Midgut of Triatoma infestans Infected with Trypanosoma cruzi

Thiol efflux mediated by an ABCC-like transporter participates forTrypanosoma cruziadaptation to environmental and chemotherapeutic stresses

Oxidative Stress and DNA Lesions: The Role of 8-Oxoguanine Lesions in Trypanosoma cruzi Cell Viability

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