Expression, Functionality, and Localization of Apurinic-Apyrimidinic Endonucleases in Replicative and Non‐Replicative Forms of Trypanosoma cruziReportar como inadecuado




Expression, Functionality, and Localization of Apurinic-Apyrimidinic Endonucleases in Replicative and Non‐Replicative Forms of Trypanosoma cruzi - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Resumen

Trypanosoma cruzi is the etiological agent of Chagas disease. The parasite has to overcome oxidative damage by ROS-RNS all along its life cycleto survive and to establish a chronic infection. We propose that T. cruzi is able to survive, among other mechanisms of detoxification, by repair ofits damaged DNA through activation of the DNA base excision repair BER pathway. BER is highly conserved in eukaryotes with apurinic-apirimidinic endonucleases APEs playing a fundamental role. Previous results showed that T. cruzi exposed to hydrogen peroxide andperoxinitrite significantly decreases its viability when co‐incubated with methoxyamine, an AP endonuclease inhibitor. In this work thelocalization, expression and functionality of two T. cruzi APEs TcAP1, Homo sapiens APE1 orthologous and TcAP2, orthologous to Homosapiens APE2 and to Schizosaccaromyces pombe Apn2p were determined. These enzymes are present and active in the two replicative parasiteforms epimastigotes and amastigotes as well as in the non‐replicative, infective trypomastigotes. TcAP1 and TcAP2 are located in the nucleus ofepimastigotes and their expression is constitutive. Epimastigote AP endonucleases as well as recombinant TcAP1 and TcAP2 are inhibited bymethoxyamine. Overexpression of TcAP1 increases epimastigotes viability when they are exposed to acute ROS-RNS attack. This protectiveeffect is more evident when parasites are submitted to persistent ROS-RNS exposition, mimicking nature conditions. Our results confirm that theBER pathway is involved in T. cruzi resistance to DNA oxidative damage and points to the participation of DNA AP endonucleases in parasitesurvival. J. Cell. Biochem.Nota general

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Autor: Sepúlveda, S.; - Valenzuela, L.; - Ponce, I.; - Cabrera Vallejos, Gonzalo; - Sierra, S.; - Bahamondes, P.; - Ramírez, S.; - Roj

Fuente: http://repositorio.uchile.cl/



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