article
TAT-mediated transduction of bacterial redox proteins generates a cytoprotective effect on neuronal cells
Autor
Balaban, Cecilia Lucía
Banchio, Claudia
Ceccarelli, Eduardo Augusto
Institución
Resumen
Cell penetrating peptides, also known as protein transduction domains, have the capacity to
ubiquitously cross cellular membranes carrying many different cargos with negligible cytotoxicity. As a result, they have emerged as a powerful tool for macromolecular deliverybased therapies. In this study, catalytically active bacterial Ferredoxin-NADP+ reductase
(LepFNR) and Heme oxygenase (LepHO) fused to the HIV TAT-derived protein transduction peptide (TAT) were efficiently transduced to neuroblastoma SHSY-5Y cells. Proteins
entered the cells through an endocytic pathway showing a time/concentration dependent
mechanism that was clearly modulated by the nature of the cargo protein. Since ferredoxinNADP+ reductases and heme oxygenases have been implicated in mechanisms of oxidative
stress defense, neuroblastoma cells simultaneously transduced with TAT-LepFNR and
TAT-LepHO were challenged by H2O2 incubations to judge the cytoprotective power of
these bacterial enzymes. Accumulation of reactive oxygen species was significantly
reduced in these transduced neuronal cells. Moreover, measurements of metabolic viability,
membrane integrity, and cell survival indicated that these cells showed a better tolerance to
oxidative stress. Our results open the possibility for the application of transducible active
redox proteins to overcome the damage elicited by oxidative stress in cells and tissues. Para citar este articulo: Balaban CL, Banchio C, Ceccarelli EA (2017) TAT-mediated transduction of bacterial redox proteins generates a cytoprotective effect on neuronal cells. PLoS ONE 12(9): e0184617. https:// doi.org/10.1371/journal.pone.0184617 Fil: Balaban, Cecilia Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Banchio, Claudia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Ceccarelli, Eduardo A. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.