INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Functional studies of Cytochrome P450 reductases from Trypanosoma cruzi.
Autor/es:
PORTAL, PATRICIO; TORRES, HÉCTOR N; FLAWIÁ, MIRTHA M.; PAVETO, CRISTINA
Lugar:
Puerto Madryn-Argentina
Reunión:
Congreso; XLVI Reunión Anual de SAIB; 2010
Institución organizadora:
SAIB
Resumen:
Trypanosoma cruzi encounters extreme fluctuations in environmental conditions during its digenetic life cycle. Modifications in lipid composition of membranes are made during metacyclogenesis in order to achieve relevant morphological and functional changes in the parasite for adaptation to the environment. Moreover, depletion of ergosterol causes trypanosomal cell death, and enzymes of this biosynthetic pathway have been proposed as targets for an antiparasitic therapy. In our laboratory, we have identified and characterized a gene family consisting of three putative Cytochrome P450 reductases (CPR) in T. cruzi named TcCPR-A, TcCPR-B and TcCPR-C. Ergosterol content was significantly increased in TcCPR-B and TcCPR-C overexpressing parasites. Nevertheless, overexpression of TcCPR-A was lethal, displaying aberrant cells, with abnormal morphology and ultrastructural alterations. Interestingly, it was recently reported that Tah18, a yeast orthologue for T. cruzi CPR-A, plays a “pro-death” role in response to oxidative stress, inducing cell death pathways. We are nowadays also studying a possible participation of this CPR in stress induced apoptosis mechanisms in T. cruzi. In order to establish the particular role of these enzymes in the mentioned processes, complementation assays are being performed using a cpr knock-out Saccharomyces cerevisiae strain (cpr-).