Proline Modulates the Trypanosoma cruzi Resistance to Reactive Oxygen Species and Drugs through a Novel D, L-Proline Transporter
| العنوان: | Proline Modulates the Trypanosoma cruzi Resistance to Reactive Oxygen Species and Drugs through a Novel D, L-Proline Transporter |
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| المؤلفون: | Claudio A. Pereira, Mariana R. Miranda, María de los Milagros Camara, Melisa Sayé, Fabio Di Girolamo |
| المصدر: | PLoS ONE PLoS ONE, Vol 9, Iss 3, p e92028 (2014) CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| بيانات النشر: | Public Library of Science, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Drug Resistance, Protozoan Proteins, Protozoology, Biochemistry, purl.org/becyt/ford/1 [https], Transmembrane Transport Proteins, Proline transport, OXIDATIVE STRESS, Amino Acids, chemistry.chemical_classification, Protozoans, Multidisciplinary, biology, Bioquímica y Biología Molecular, Trypanocidal Agents, Amino acid, DRUG RESISTANCE, Chemistry, Protein Transport, Organic Acids, Benznidazole, Physical Sciences, Medicine, CIENCIAS NATURALES Y EXACTAS, medicine.drug, Research Article, Subcellular Fractions, Trypanosoma, Proline, Science, Trypanosoma cruzi, Saccharomyces cerevisiae, Microbiology, Ciencias Biológicas, Stress, Physiological, medicine, Nifurtimox, purl.org/becyt/ford/1.6 [https], Reactive oxygen species, Life Cycle Stages, Organisms, Parasite Physiology, Chemical Compounds, Biology and Life Sciences, Proteins, Computational Biology, Biological Transport, Metabolism, TRYPANOSOMA CRUZI, biology.organism_classification, Parasitic Protozoans, Amino Acid Transport Systems, Neutral, chemistry, PROLINE TRANSPORT, D,L-PROLINE, Parasitology, Energy Metabolism, Reactive Oxygen Species, Acids |
| الوصف: | Trypanosoma cruzi, the etiological agent of Chagas' disease, has a metabolism largely based on the consumption of glucose and proline. This amino acid is essential for host cells infection and intracellular differentiation. In this work we identified a proline transporter (TcAAAP069) by yeasts complementation assays and overexpression in Trypanosoma cruzi epimastigotes. TcAAAP069 is mono-specific for proline but presents an unusual feature; the lack of stereospecificity, because it is competitively inhibited by the D- enantiomer. Parasites overexpressing TcAAAP069 have an increased intracellular proline concentration, 2.6-fold higher than controls, as a consequence of a higher proline transport rate. Furthermore, augmented proline concentration correlates with an improved resistance to trypanocidal drugs and also to reactive oxygen species including hydrogen peroxide and nitric oxide, emulating natural physiological situations. The IC50s for nifurtimox, benznidazole, H2O2 and NO. were 125%, 68%, 44% and 112% higher than controls, respectively. Finally, proline metabolism generates a higher concentration (48%) of ATP in TcAAAP069 parasites. Since proline participates on essential energy pathways, stress and drug resistance responses, these results provide a novel target for the development of new drugs for the treatments for Chagas' disease. Fil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Miranda, Mariana Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Di Girolamo, Fabio Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Camara, María de los Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3a2930b21e55534879934df806d69fbTest http://europepmc.org/articles/PMC3956872Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f3a2930b21e55534879934df806d69fb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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