دورية أكاديمية
أعرض في EDS

Oxidative stress and DNA lesions: the role of 8-oxoguanine lesions in Trypanosoma cruzi cell viability.

التفاصيل البيبلوغرافية
العنوان: Oxidative stress and DNA lesions: the role of 8-oxoguanine lesions in Trypanosoma cruzi cell viability.
المؤلفون: Aguiar PH; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas - UFMG, Belo Horizonte, Minas Gerais, Brazil., Furtado C, Repolês BM, Ribeiro GA, Mendes IC, Peloso EF, Gadelha FR, Macedo AM, Franco GR, Pena SD, Teixeira SM, Vieira LQ, Guarneri AA, Andrade LO, Machado CR
المصدر: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2013 Jun 13; Vol. 7 (6), pp. e2279. Date of Electronic Publication: 2013 Jun 13 (Print Publication: 2013).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: DNA Damage* , Oxidative Stress*, Guanine/*analogs & derivatives , Trypanosoma cruzi/*physiology, Animals ; Cell Survival ; Cells, Cultured ; Chagas Disease/parasitology ; Chagas Disease/pathology ; Disease Models, Animal ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Female ; Fibroblasts/parasitology ; Gene Expression ; Guanine/metabolism ; Hydrogen Peroxide/toxicity ; Macrophages/parasitology ; Mice ; Molecular Sequence Data ; Oxidoreductases Acting on CH-NH Group Donors/genetics ; Oxidoreductases Acting on CH-NH Group Donors/metabolism ; Parasitemia/parasitology ; Parasitemia/pathology ; Pyrophosphatases/genetics ; Pyrophosphatases/metabolism ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Sequence Analysis, DNA ; Trypanosoma cruzi/drug effects ; Trypanosoma cruzi/enzymology ; Trypanosoma cruzi/growth & development
مستخلص: 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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سلسلة جزيئية: GENBANK KC630985
المشرفين على المادة: 0 (Escherichia coli Proteins)
0 (Recombinant Proteins)
5614-64-2 (8-hydroxyguanine)
5Z93L87A1R (Guanine)
BBX060AN9V (Hydrogen Peroxide)
EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors)
EC 1.5.99.- (methylenetetrahydromethanopterin dehydrogenase)
EC 3.6.1.- (Pyrophosphatases)
EC 3.6.1.- (mutT protein, E coli)
تواريخ الأحداث: Date Created: 20130621 Date Completed: 20131216 Latest Revision: 20240530
رمز التحديث: 20240530
مُعرف محوري في PubMed: PMC3681716
DOI: 10.1371/journal.pntd.0002279
PMID: 23785540
قاعدة البيانات: MEDLINE
الوصف
تدمد:1935-2735
DOI:10.1371/journal.pntd.0002279